86. Shaheen K, Alraies MC, Alraiyes AH, Christie R (April 2012). \"Factor V Leiden: how great isthe risk of venous thromboembolism?\" (https://www.ccjm.org/content/79/4/265.long).Cleveland Clinic Journal of Medicine. 79 (4): 265–72. doi 10.3949/ccjm.79a.11072 (https://do:i.org/10.3949%2Fccjm.79a.11072) PMID 22473726 (https://pubmed.ncbi.nlm.nih.gov/22473. 726) S2CID 23139811 (https://api.semanticscholar.org/CorpusID:23139811). .87. Varga EA, Kujovich JL (January 2012). \"Management of inherited thrombophilia: guide forgenetics professionals\". Clinical Genetics. 81 (1): 7–17. doi 10.1111/j.1399-:0004.2011.01746.x (https://doi.org/10.1111%2Fj.1399-0004.2011.01746.x) PMID 21707594. (https://pubmed.ncbi.nlm.nih.gov/21707594) S2CID 9305488 (https://api.semanticscholar.or. g/CorpusID:9305488).88. Dentali F, Sironi AP, Ageno W, Turato S, Bonfanti C, Frattini F, et al. (July 2012). \"Non-Oblood type is the commonest genetic risk factor for VTE: results from a meta-analysis of theliterature\". Seminars in Thrombosis and Hemostasis. 38 (5): 535–48. doi 10.1055/s-0032-:1315758 (https://doi.org/10.1055%2Fs-0032-1315758) PMID 22740183 (https://pubmed.ncb. i.nlm.nih.gov/22740183).89. Paulsen B, Skille H, Smith EN, Hveem K, Gabrielsen ME, Brækkan SK, et al. (October2019). \"Fibrinogen gamma gene rs2066865 and risk of cancer-related venousthromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327659).Haematologica. 105 (7): 1963–68. doi 10.3324/haematol.2019.224279 (https://doi.org/10.332:4%2Fhaematol.2019.224279) PMC 7327659 (https://www.ncbi.nlm.nih.gov/pmc/articles/PM. C7327659) PMID 31582554 (https://pubmed.ncbi.nlm.nih.gov/31582554). .90. Eslamiyeh H, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M (2015). \"Homocystinuria: a raredisorder presenting as cerebral sinovenous thrombosis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515342). Iranian Journal of Child Neurology. (2): 53–57. 9PMC 4515342 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515342) PMID 26221164 (https://pubmed.ncbi.nlm.. nih.gov/26221164).91. Ortel TL, Erkan D, Kitchens CS (September 2015). \"How I treat catastrophic thromboticsyndromes\" (https://doi.org/10.1182%2Fblood-2014-09-551978). Blood. 126 (11): 1285–93.doi 10.1182/blood-2014-09-551978 (https://doi.org/10.1182%2Fblood-2014-09-551978):.PMID 26179082 (https://pubmed.ncbi.nlm.nih.gov/26179082).92. Lazo-Langner A, Kovacs MJ, Hedley B, Al-Ani F, Keeney M, Louzada ML, et al. (June 2015).\"Screening of patients with idiopathic venous thromboembolism for paroxysmal nocturnalhemoglobinuria clones\". Thrombosis Research. 135 (6): 1107–09.doi 10.1016/j.thromres.2015.04.006 (https://doi.org/10.1016%2Fj.thromres.2015.04.006):.PMID 25890452 (https://pubmed.ncbi.nlm.nih.gov/25890452).93. Lu HY, Liao KM (August 2018). \"Increased risk of deep vein thrombosis in end-stage renaldisease patients\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097196). BMCNephrology. 19 (1): 204. doi 10.1186/s12882-018-0989-z (https://doi.org/10.1186%2Fs12882:-018-0989-z) PMC 6097196 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097196). .PMID 30115029 (https://pubmed.ncbi.nlm.nih.gov/30115029).94. Reikvam H, Tiu RV (April 2012). \"Venous thromboembolism in patients with essentialthrombocythemia and polycythemia vera\" (https://doi.org/10.1038%2Fleu.2011.314).Leukemia. 26 (4): 563–71. doi 10.1038/leu.2011.314 (https://doi.org/10.1038%2Fleu.2011.31:4) PMID 22076463 (https://pubmed.ncbi.nlm.nih.gov/22076463). .95. Kyrle PA, Eichinger S (2005). \"Deep vein thrombosis\". Lancet. 365 (9465): 1163–74.doi 10.1016/S0140-6736(05)71880-8 (https://doi.org/10.1016%2FS0140-6736%2805%2971:880-8) PMID 15794972 (https://pubmed.ncbi.nlm.nih.gov/15794972) S2CID 54379879 (http. . s://api.semanticscholar.org/CorpusID:54379879).96. McLendon K, Goyal A, Bansal P, Attia M (2020). \"Deep venous thrombosis risk factors\" (https://www.ncbi.nlm.nih.gov/books/NBK470215/). StatPearls [Internet]. Treasure Island, FL.PMID 29262230 (https://pubmed.ncbi.nlm.nih.gov/29262230).97. Middeldorp S (2011). \"Is thrombophilia testing useful?\". Hematology. American Society ofHematology. Education Program. 2011 (1): 150–55. doi 10.1182/asheducation-2011.1.150 (ht:tps://doi.org/10.1182%2Fasheducation-2011.1.150) PMID 22160027 (https://pubmed.ncbi.nl. m.nih.gov/22160027).
98. Zöller B, Svensson PJ, Dahlbäck B, Lind-Hallden C, Hallden C, Elf J (September 2020).\"Genetic risk factors for venous thromboembolism\" (https://doi.org/10.1080%2F17474086.2020.1804354). Expert Review of Hematology. 13 (9): 971–81.doi 10.1080/17474086.2020.1804354 (https://doi.org/10.1080%2F17474086.2020.1804354):.PMID 32731838 (https://pubmed.ncbi.nlm.nih.gov/32731838).99. Palareti G, Schellong S (January 2012). \"Isolated distal deep vein thrombosis: what we knowand what we are doing\" (https://doi.org/10.1111%2Fj.1538-7836.2011.04564.x). Journal ofThrombosis and Haemostasis. 10 (1): 11–19. doi 10.1111/j.1538-7836.2011.04564.x (https://d:oi.org/10.1111%2Fj.1538-7836.2011.04564.x) PMID 22082302 (https://pubmed.ncbi.nlm.nih.. gov/22082302).100. Chapin JC, Hajjar KA (January 2015). \"Fibrinolysis and the control of blood coagulation\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314363). Blood Reviews. 29 (1): 17–24.doi 10.1016/j.blre.2014.09.003 (https://doi.org/10.1016%2Fj.blre.2014.09.003):.PMC 4314363 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314363) PMID 25294122 (ht. tps://pubmed.ncbi.nlm.nih.gov/25294122).101. Chan WS, Spencer FA, Ginsberg JS (April 2010). \"Anatomic distribution of deep veinthrombosis in pregnancy\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855912).Canadian Medical Association Journal. 182 (7): 657–60. doi 10.1503/cmaj.091692 (https://do:i.org/10.1503%2Fcmaj.091692) PMC 2855912 (https://www.ncbi.nlm.nih.gov/pmc/articles/P. MC2855912) PMID 20351121 (https://pubmed.ncbi.nlm.nih.gov/20351121). .102. Kim ES, Bartholomew JR. \"Venous thromboembolism\" (http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/venous-thromboembolism/). DiseaseManagement Project. Cleveland Clinic. Archived (https://web.archive.org/web/20110223211240/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/venous%2Dthromboembolism/) from the original on 23 February 2011. Retrieved 15 February2011.103. Saha P, Humphries J, Modarai B, Mattock K, Waltham M, Evans CE, et al. (March 2011).\"Leukocytes and the natural history of deep vein thrombosis: current concepts and futuredirections\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079895). Arteriosclerosis,Thrombosis, and Vascular Biology. 31 (3): 506–12. doi 10.1161/ATVBAHA.110.213405 (http:s://doi.org/10.1161%2FATVBAHA.110.213405) PMC 3079895 (https://www.ncbi.nlm.nih.gov/. pmc/articles/PMC3079895) PMID 21325673 (https://pubmed.ncbi.nlm.nih.gov/21325673). .104. Ro A, Kageyama N, Mukai T (June 2017). \"Pathophysiology of venous thromboembolismwith respect to the anatomical features of the deep veins of lower limbs: a review\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579784). Annals of Vascular Diseases. 10 (2): 99–106.doi 10.3400/avd.ra.17-00035 (https://doi.org/10.3400%2Favd.ra.17-00035) PMC 5579784 (h:. ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579784) PMID 29034034 (https://pubmed.nc. bi.nlm.nih.gov/29034034).105. Nicklas JM, Gordon AE, Henke PK (March 2020). \"Resolution of deep venous thrombosis:proposed immune paradigms\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139924).International Journal of Molecular Sciences. 21 (6): 2080. doi 10.3390/ijms21062080 (https://:doi.org/10.3390%2Fijms21062080) PMC 7139924 (https://www.ncbi.nlm.nih.gov/pmc/article. s/PMC7139924) PMID 32197363 (https://pubmed.ncbi.nlm.nih.gov/32197363). .106. López JA, Chen J (2009). \"Pathophysiology of venous thrombosis\". Thrombosis Research.123 (Suppl 4): S30–34. doi 10.1016/S0049-3848(09)70140-9 (https://doi.org/10.1016%2FS0:049-3848%2809%2970140-9) PMID 19303501 (https://pubmed.ncbi.nlm.nih.gov/19303501). .107. Swystun LL, Liaw PC (August 2016). \"The role of leukocytes in thrombosis\" (https://doi.org/10.1182%2Fblood-2016-05-718114). Blood. 128 (6): 753–62. doi 10.1182/blood-2016-05-:718114 (https://doi.org/10.1182%2Fblood-2016-05-718114) PMID 27354721 (https://pubme. d.ncbi.nlm.nih.gov/27354721).
108. Thålin C, Hisada Y, Lundström S, Mackman N, Wallén H (September 2019). \"Neutrophilextracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis\"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703916). Arteriosclerosis, Thrombosis, andVascular Biology. 39 (9): 1724–38. doi 10.1161/ATVBAHA.119.312463 (https://doi.org/10.116:1%2FATVBAHA.119.312463) PMC 6703916 (https://www.ncbi.nlm.nih.gov/pmc/articles/PM. C6703916) PMID 31315434 (https://pubmed.ncbi.nlm.nih.gov/31315434). .109. Laridan E, Martinod K, De Meyer SF (February 2019). \"Neutrophil Extracellular Traps inArterial and Venous Thrombosis\" (https://lirias.kuleuven.be/handle/123456789/633069).Seminars in Thrombosis and Hemostasis. 45 (1): 86–93. doi 10.1055/s-0038-1677040 (http:s://doi.org/10.1055%2Fs-0038-1677040) PMID 30634198 (https://pubmed.ncbi.nlm.nih.gov/. 30634198) S2CID 58594612 (https://api.semanticscholar.org/CorpusID:58594612). .110. Myers DD (March 2015). \"Pathophysiology of venous thrombosis\". Phlebology. 30 (1 Suppl):7–13. doi 10.1177/0268355515569424 (https://doi.org/10.1177%2F0268355515569424):.PMID 25729062 (https://pubmed.ncbi.nlm.nih.gov/25729062) S2CID 22467822 (https://api.s. emanticscholar.org/CorpusID:22467822).111. Fernandes CJ, Morinaga LTK, Alves JL, Castro MA, Calderaro D, Jardim CVP, et al. (March2019). \"Cancer-associated thrombosis: the when, how and why\" (https://doi.org/10.1183%2F16000617.0119-2018). European Respiratory Review. 28 (151): 180119.doi 10.1183/16000617.0119-2018 (https://doi.org/10.1183%2F16000617.0119-2018):.PMID 30918022 (https://pubmed.ncbi.nlm.nih.gov/30918022).112. \"DDI/9290 clinical: D-dimer, plasma\" (https://web.archive.org/web/20121008203101/http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9290). Mayo MedicalLaboratories. Archived from the original (http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9290) on 8 October 2012. Retrieved 27 August 2012.113. Vedantham S, Goldhaber SZ, Kahn SR, Julian J, Magnuson E, Jaff MR, et al. (April 2013).\"Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluatepharmacomechanical catheter-directed thrombolysis for the prevention of postthromboticsyndrome in patients with proximal deep vein thrombosis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612268). American Heart Journal. 165 (4): 523–530.e3.doi 10.1016/j.ahj.2013.01.024 (https://doi.org/10.1016%2Fj.ahj.2013.01.024) PMC 3612268:. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612268) PMID 23537968 (https://pubmed.n. cbi.nlm.nih.gov/23537968).114. Geersing GJ, Zuithoff NP, Kearon C, Anderson DR, Ten Cate-Hoek AJ, Elf JL, et al. (March2014). \"Exclusion of deep vein thrombosis using the Wells rule in clinically importantsubgroups: individual patient data meta-analysis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948465). BMJ. 348 (7949): g1340. doi 10.1136/bmj.g1340 (https://doi.org/10.1136%2F:bmj.g1340) PMC 3948465 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948465). .PMID 24615063 (https://pubmed.ncbi.nlm.nih.gov/24615063).115. Pyzocha N (December 2019). \"Diagnosing DVT in nonpregnant adults in the primary caresetting\" (https://www.aafp.org/afp/2019/1215/p778.html). American Family Physician. 100(12): 778–80. PMID 31845779 (https://pubmed.ncbi.nlm.nih.gov/31845779).116. Stone J, Hangge P, Albadawi H, Wallace A, Shamoun F, Knuttien MG, et al. (December2017). \"Deep vein thrombosis: pathogenesis, diagnosis, and medical management\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778510). Cardiovascular Diagnosis and Therapy. 7(Suppl 3): S276–84. doi 10.21037/cdt.2017.09.01 (https://doi.org/10.21037%2Fcdt.2017.09.0:1) PMC 5778510 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778510) PMID 29399531. . (https://pubmed.ncbi.nlm.nih.gov/29399531).117. Wells PS, Ihaddadene R, Reilly A, Forgie MA (January 2018). \"Diagnosis of venousthromboembolism: 20 years of progress\". Annals of Internal Medicine. 168 (2): 131–40.doi 10.7326/M17-0291 (https://doi.org/10.7326%2FM17-0291) PMID 29310137 (https://pub:. med.ncbi.nlm.nih.gov/29310137) S2CID 34220435 (https://api.semanticscholar.org/CorpusI. D:34220435).
118. Le Gal G, Righini M (June 2015). \"Controversies in the diagnosis of venousthromboembolism\" (https://doi.org/10.1111%2Fjth.12937). Journal of Thrombosis andHaemostasis. 13 Suppl 1: S259–65. doi 10.1111/jth.12937 (https://doi.org/10.1111%2Fjth.129:37) PMID 26149033 (https://pubmed.ncbi.nlm.nih.gov/26149033). .119. Rahaghi FN, Minhas JK, Heresi GA (September 2018). \"Diagnosis of deep venousthrombosis and pulmonary embolism: new imaging tools and modalities\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317734). Clinics in Chest Medicine. 39 (3): 493–504.doi 10.1016/j.ccm.2018.04.003 (https://doi.org/10.1016%2Fj.ccm.2018.04.003):.PMC 6317734 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317734) PMID 30122174 (ht. tps://pubmed.ncbi.nlm.nih.gov/30122174).120. Häggström, M (January 2019). \"Subsartorial vessels as replacement names for superficialfemoral vessels\" (http://www.ijars.net/articles/PDF/2458/40329_CE%5BRa1%5D_F(SHU)_PF1(A_SHU)_PFA(A_SHU)_PF2(AKA_SHU)_PN(SHU).pdf) (PDF). International Journal ofAnatomy, Radiology and Surgery. (1): AV01–02. 8doi 10.7860/IJARS/2019/40329:2458 (http:s://doi.org/10.7860%2FIJARS%2F2019%2F40329%3A2458).121. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. (April2011). \"Management of massive and submassive pulmonary embolism, iliofemoral deep veinthrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement fromthe American Heart Association\" (https://doi.org/10.1161%2FCIR.0b013e318214914f).Circulation. 123 (16): 1788–830. doi 10.1161/CIR.0b013e318214914f (https://doi.org/10.116:1%2FCIR.0b013e318214914f) PMID 21422387. (https://pubmed.ncbi.nlm.nih.gov/21422387).122. Cundiff DK, Manyemba J, Pezzullo JC (January 2006). Cundiff DK (ed.). \"Anticoagulantsversus non-steroidal anti-inflammatories or placebo for treatment of venousthromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389637). The CochraneDatabase of Systematic Reviews (1): CD003746. doi 10.1002/14651858.CD003746.pub2 (ht:tps://doi.org/10.1002%2F14651858.CD003746.pub2) PMC 7389637 (https://www.ncbi.nlm.n. ih.gov/pmc/articles/PMC7389637) PMID 16437461 (https://pubmed.ncbi.nlm.nih.gov/164374. 61).123. Fleck D, Albadawi H, Wallace A, Knuttinen G, Naidu S, Oklu R (December 2017). \"Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778527). Cardiovascular Diagnosis and Therapy. (Suppl 3):7S134–39. doi 10.21037/cdt.2017.11.03 (https://doi.org/10.21037%2Fcdt.2017.11.03):.PMC 5778527 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778527) PMID 29399516 (ht. tps://pubmed.ncbi.nlm.nih.gov/29399516).124. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. (February 2016).\"Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report\". Chest.149 (2): 315–52. doi 10.1016/j.chest.2015.11.026 (https://doi.org/10.1016%2Fj.chest.2015.1:1.026) PMID 26867832 (https://pubmed.ncbi.nlm.nih.gov/26867832). .125. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. (February2012). \"Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention ofthrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practiceguidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278049). Chest. 141 (2 Suppl):e419S–96S. doi 10.1378/chest.11-2301 (https://doi.org/10.1378%2Fchest.11-2301):.PMC 3278049 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278049) PMID 22315268 (ht. tps://pubmed.ncbi.nlm.nih.gov/22315268).126. Shikdar S, Vashisht R, Bhattacharya PT (2021). \"International normalized ratio (INR)\" (https://www.ncbi.nlm.nih.gov/books/NBK507707/). StatPearls [Internet]. Treasure Island, FL.PMID 29939529 (https://pubmed.ncbi.nlm.nih.gov/29939529).127. Guyatt et al. 2012, p. 22S: 3.2.
128. Middeldorp S, Prins MH, Hutten BA (August 2014). \"Duration of treatment with vitamin Kantagonists in symptomatic venous thromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074008). The Cochrane Database of Systematic Reviews (8): CD001367.doi 10.1002/14651858.CD001367.pub3 (https://doi.org/10.1002%2F14651858.CD001367.pu:b3) PMC 7074008 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074008). .PMID 25092359 (https://pubmed.ncbi.nlm.nih.gov/25092359).129. de Jong PG, Coppens M, Middeldorp S (August 2012). \"Duration of anticoagulant therapy forvenous thromboembolism: balancing benefits and harms on the long term\" (https://doi.org/10.1111%2Fj.1365-2141.2012.09196.x). British Journal of Haematology. 158 (4): 433–41.doi 10.1111/j.1365-2141.2012.09196.x (https://doi.org/10.1111%2Fj.1365-2141.2012.09196.:x) PMID 22734929 (https://pubmed.ncbi.nlm.nih.gov/22734929). .130. Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. (November 2018).\"American Society of Hematology 2018 guidelines for management of venousthromboembolism: optimal management of anticoagulation therapy\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258922). Blood Advances. (22): 3257–91.2doi 10.1182/bloodadvances.2018024893 (https://doi.org/10.1182%2Fbloodadvances.201802:4893) PMC 6258922 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258922). .PMID 30482765 (https://pubmed.ncbi.nlm.nih.gov/30482765).131. Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, et al. (August 2011). \"Guidelines onoral anticoagulation with warfarin – fourth edition\" (https://doi.org/10.1111%2Fj.1365-2141.2011.08753.x). British Journal of Haematology. 154 (3): 311–24. doi 10.1111/j.1365-:2141.2011.08753.x (https://doi.org/10.1111%2Fj.1365-2141.2011.08753.x) PMID 21671894. (https://pubmed.ncbi.nlm.nih.gov/21671894).132. Douketis J, Tosetto A, Marcucci M, Baglin T, Cushman M, Eichinger S, et al. (October 2010).\"Patient-level meta-analysis: effect of measurement timing, threshold, and patient age onability of D-dimer testing to assess recurrence risk after unprovoked venousthromboembolism\". Annals of Internal Medicine. 153 (8): 523–31. doi 10.7326/0003-4819-:153-8-201010190-00009 (https://doi.org/10.7326%2F0003-4819-153-8-201010190-00009).PMID 20956709 (https://pubmed.ncbi.nlm.nih.gov/20956709) S2CID 10659607 (https://api.s. emanticscholar.org/CorpusID:10659607).133. Chatsis V, Visintini S (January 2017). Early mobilization for patients with venousthromboembolism: a review of clinical effectiveness and guidelines (https://www.ncbi.nlm.nih.gov/books/NBK531715/) (Report). Ottawa, ON: Canadian Agency for Drugs andTechnologies in Health. PMID 30303669 (https://pubmed.ncbi.nlm.nih.gov/30303669).134. Berntsen CF, Kristiansen A, Akl EA, Sandset PM, Jacobsen EM, Guyatt G, et al. (April 2016).\"Compression Stockings for Preventing the Postthrombotic Syndrome in Patients with DeepVein Thrombosis\". The American Journal of Medicine. 129 (4): 447.e1–447.e20.doi 10.1016/j.amjmed.2015.11.031 (https://doi.org/10.1016%2Fj.amjmed.2015.11.031):.PMID 26747198 (https://pubmed.ncbi.nlm.nih.gov/26747198).135. Wigle P, Hein B, Bernheisel CR (October 2019). \"Anticoagulation: updated guidelines foroutpatient management\" (https://www.aafp.org/afp/2019/1001/p426.html). American FamilyPhysician. 100 (7): 426–34. PMID 31573167 (https://pubmed.ncbi.nlm.nih.gov/31573167).136. Wallace A, Albadawi H, Hoang P, Fleck A, Naidu S, Knuttinen G, et al. (December 2017).\"Statins as a preventative therapy for venous thromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778529). Cardiovascular Diagnosis and Therapy. (Suppl 3): S207–18.7doi 10.21037/cdt.2017.09.12 (https://doi.org/10.21037%2Fcdt.2017.09.12) PMC 5778529 (ht:. tps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778529) PMID 29399524 (https://pubmed.ncb. i.nlm.nih.gov/29399524).137. National Institute for Health and Care Excellence. \"NICE Guideline 158: Venousthromboembolic diseases: diagnosis, management and thrombophilia testing (https://www.nice.org.uk/guidance/ng158)\" London, 26 March 2020.
138. Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, et al. (January 2012).\"Long-term outcome after additional catheter-directed thrombolysis versus standardtreatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomisedcontrolled trial\". Lancet. 379 (9810): 31–38. doi 10.1016/S0140-6736(11)61753-4 (https://doi.:org/10.1016%2FS0140-6736%2811%2961753-4) PMID 22172244 (https://pubmed.ncbi.nlm.. nih.gov/22172244) S2CID 21801157 (https://api.semanticscholar.org/CorpusID:21801157). .139. Haig Y, Enden T, Grøtta O, Kløw NE, Slagsvold CE, Ghanima W, et al. (February 2016).\"Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis(CaVenT): 5-year follow-up results of an open-label, randomised controlled trial\". The LancetHaematology. (2): e64–71. 3doi 10.1016/S2352-3026(15)00248-3 (https://doi.org/10.1016%:2FS2352-3026%2815%2900248-3) PMID 26853645 (https://pubmed.ncbi.nlm.nih.gov/2685. 3645).140. Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al. (December2017). \"Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763501). The New England Journal of Medicine.377 (23): 2240–52. doi 10.1056/NEJMoa1615066 (https://doi.org/10.1056%2FNEJMoa16150:66) PMC 5763501 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763501). .PMID 29211671 (https://pubmed.ncbi.nlm.nih.gov/29211671).141. Bhandari T (6 December 2017). \"Clot-busting drugs not recommended for most patients withblood clots\" (https://medicine.wustl.edu/news/clot-busting-drugs-not-recommended-most-patients-with-blood-clots/). Washington University School of Medicine. Retrieved 21 January2020.142. National Institute for Health and Care Excellence. \"NICE Interventional procedures guidance651: Percutaneous mechanical thrombectomy for acute deep vein thrombosis of the leg (https://www.nice.org.uk/guidance/ipg651)\" London, 12 June 2019.143. Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, et al. (February 2019).\"Endovascular thrombus removal for acute iliofemoral deep vein thrombosis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389417). Circulation. 139 (9): 1162–73.doi 10.1161/CIRCULATIONAHA.118.037425 (https://doi.org/10.1161%2FCIRCULATIONAH:A.118.037425) PMC 6389417 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389417). .PMID 30586751 (https://pubmed.ncbi.nlm.nih.gov/30586751).144. Magnuson EA, Chinnakondepalli K, Vilain K, Kearon C, Julian JA, Kahn SR, et al. (October2019). \"Cost-effectiveness of pharmacomechanical catheter-directed thrombolysis versusstandard anticoagulation in patients with proximal deep vein thrombosis: results from theATTRACT trial\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788761). Circulation:Cardiovascular Quality and Outcomes. 12 (10): e005659.doi 10.1161/CIRCOUTCOMES.119.005659 (https://doi.org/10.1161%2FCIRCOUTCOMES.1:19.005659) PMC 6788761 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788761). .PMID 31592728 (https://pubmed.ncbi.nlm.nih.gov/31592728).145. Jones MR, Prabhakar A, Viswanath O, Urits I, Green JB, Kendrick JB, et al. (June 2019).\"Thoracic outlet syndrome: a comprehensive review of pathophysiology, diagnosis, andtreatment\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514035). Pain and Therapy. 8(1): 5–18. doi 10.1007/s40122-019-0124-2 (https://doi.org/10.1007%2Fs40122-019-0124-2):.PMC 6514035 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514035) PMID 31037504 (ht. tps://pubmed.ncbi.nlm.nih.gov/31037504).146. Ijaopo R, Oguntolu V, DCosta D, Garnham A, Hobbs S (March 2016). \"A case of Paget-Schroetter syndrome (PSS) in a young judo tutor: a case report\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797165). Journal of Medical Case Reports. 10: 63. doi 10.1186/s13256-:016-0848-0 (https://doi.org/10.1186%2Fs13256-016-0848-0) PMC 4797165 (https://www.nc. bi.nlm.nih.gov/pmc/articles/PMC4797165) PMID 26987584 (https://pubmed.ncbi.nlm.nih.go. v/26987584).
147. Turner TE, Saeed MJ, Novak E, Brown DL (July 2018). \"Association of inferior vena cavafilter placement for venous thromboembolic disease and a contraindication to anticoagulationwith 30-day mortality\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324296). JAMANetwork Open. (3): e180452. 1doi 10.1001/jamanetworkopen.2018.0452 (https://doi.org/10.:1001%2Fjamanetworkopen.2018.0452) PMC 6324296 (https://www.ncbi.nlm.nih.gov/pmc/ar. ticles/PMC6324296) PMID 30646021 (https://pubmed.ncbi.nlm.nih.gov/30646021). .148. Moll S (9 May 2012). \"What kind of doctor do I need?\" (http://patientblog.clotconnect.org/2012/05/09/what-kind-of-doctor-do-i-need/). Clot Connect. Retrieved 28 January 2020.149. Kitchen L, Lawrence M, Speicher M, Frumkin K (July 2016). \"Emergency departmentmanagement of suspected calf-vein deep venous thrombosis: a diagnostic algorithm\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944794). The Western Journal of EmergencyMedicine. 17 (4): 384–90. doi 10.5811/westjem.2016.5.29951 (https://doi.org/10.5811%2Fwe:stjem.2016.5.29951) PMC 4944794 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC494479. 4) PMID 27429688 (https://pubmed.ncbi.nlm.nih.gov/27429688). .150. \"Inferior Vena Cava (IVC) Filter Placement\" (https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/inferior-vena-cava-ivc-filter-placement). Johns Hopkins Medicine.2020. Retrieved 28 January 2020.151. Partsch H, Blättler W (November 2000). \"Compression and walking versus bed rest in thetreatment of proximal deep venous thrombosis with low molecular weight heparin\" (https://doi.org/10.1067%2Fmva.2000.110352). Journal of Vascular Surgery. 32 (5): 861–69.doi 10.1067/mva.2000.110352 (https://doi.org/10.1067%2Fmva.2000.110352):.PMID 11054217 (https://pubmed.ncbi.nlm.nih.gov/11054217).152. Folsom AR, Cushman M (December 2020). \"Exploring opportunities for primary prevention ofunprovoked venous thromboembolism: ready for prime time?\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763794). Journal of the American Heart Association. (23): e019395.9doi 10.1161/JAHA.120.019395 (https://doi.org/10.1161%2FJAHA.120.019395):.PMC 7763794 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763794) PMID 33191841 (ht. tps://pubmed.ncbi.nlm.nih.gov/33191841).153. Li L, Zhang P, Tian JH, Yang K (December 2014). \"Statins for primary prevention of venousthromboembolism\" (https://doi.org/10.1002%2F14651858.CD008203.pub3). The CochraneDatabase of Systematic Reviews (12): CD008203. doi 10.1002/14651858.CD008203.pub3:(https://doi.org/10.1002%2F14651858.CD008203.pub3) PMID 25518837 (https://pubmed.nc. bi.nlm.nih.gov/25518837).154. Kunutsor SK, Seidu S, Khunti K (February 2017). \"Statins and primary prevention of venousthromboembolism: a systematic review and meta-analysis\" (https://research-information.bris.ac.uk/files/99752833/Statins_VTE_Lancet_Accepted.pdf) (PDF). The Lancet Haematology. 4(2): e83–e93. doi 10.1016/S2352-3026(16)30184-3 (https://doi.org/10.1016%2FS2352-302:6%2816%2930184-3) hdl 1983/5a398e70-6c7c-40bd-a8d4-53c24d84f1a2 (https://hdl.handl. :e.net/1983%2F5a398e70-6c7c-40bd-a8d4-53c24d84f1a2) PMID 28089655 (https://pubmed.. ncbi.nlm.nih.gov/28089655).155. Biere-Rafi S, Hutten BA, Squizzato A, Ageno W, Souverein PC, de Boer A, et al. (June2013). \"Statin treatment and the risk of recurrent pulmonary embolism\" (https://doi.org/10.1093%2Feurheartj%2Feht046). European Heart Journal. 34 (24): 1800–06.doi 10.1093/eurheartj/eht046 (https://doi.org/10.1093%2Feurheartj%2Feht046):.PMID 23396492 (https://pubmed.ncbi.nlm.nih.gov/23396492).156. Sobieraj DM, Lee S, Coleman CI, Tongbram V, Chen W, Colby J, et al. (May 2012).\"Prolonged versus standard-duration venous thromboprophylaxis in major orthopedicsurgery: a systematic review\". Annals of Internal Medicine. 156 (10): 720–27.doi 10.7326/0003-4819-156-10-201205150-00423 (https://doi.org/10.7326%2F0003-4819-15:6-10-201205150-00423) PMID 22412039 (https://pubmed.ncbi.nlm.nih.gov/22412039). .S2CID 22797561 (https://api.semanticscholar.org/CorpusID:22797561).
157. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. (February2012). \"Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy andprevention of thrombosis, 9th ed: American College of Chest Physicians evidence-basedclinical practice guidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278063). Chest.141 (2 Suppl): e278S–e325S. doi 10.1378/chest.11-2404 (https://doi.org/10.1378%2Fchest.1:1-2404) PMC 3278063 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278063). .PMID 22315265 (https://pubmed.ncbi.nlm.nih.gov/22315265).158. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. (February 2012).\"Prevention of VTE in nonorthopedic surgical patients: Antithrombotic therapy and preventionof thrombosis, 9th ed: American College of Chest Physicians evidence-based clinicalpractice guidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278061). Chest. 141 (2Suppl): e227S–77S. doi 10.1378/chest.11-2297 (https://doi.org/10.1378%2Fchest.11-2297):.PMC 3278061 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278061) PMID 22315263 (ht. tps://pubmed.ncbi.nlm.nih.gov/22315263).159. Bates SM, Rajasekhar A, Middeldorp S, McLintock C, Rodger MA, James AH, et al.(November 2018). \"American Society of Hematology 2018 guidelines for management ofvenous thromboembolism: venous thromboembolism in the context of pregnancy\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258928). Blood Advances. (22): 3317–59.2doi 10.1182/bloodadvances.2018024802 (https://doi.org/10.1182%2Fbloodadvances.201802:4802) PMC 6258928 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258928). .PMID 30482767 (https://pubmed.ncbi.nlm.nih.gov/30482767).160. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO (February 2012).\"VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic therapy andprevention of thrombosis, 9th ed: American College of Chest Physicians evidence-basedclinical practice guidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278054). Chest.141 (2 Suppl): e691S–e736S. doi 10.1378/chest.11-2300 (https://doi.org/10.1378%2Fchest.1:1-2300) PMC 3278054 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278054). .PMID 22315276 (https://pubmed.ncbi.nlm.nih.gov/22315276).161. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. (February 2012).\"Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention ofThrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical PracticeGuidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278052). Chest. 141 (2 Suppl):e195S–e226S. doi 10.1378/chest.11-2296 (https://doi.org/10.1378%2Fchest.11-2296):.PMC 3278052 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278052) PMID 22315261 (ht. tps://pubmed.ncbi.nlm.nih.gov/22315261). See section 6.0, Long-Distance Travel162. \"New DVT guidelines: No evidence to support \"economy-class syndrome\" \" (http://www.chestnet.org/News/Press-Releases/2012/02/ACCP-Antithrombotic-and-Economy-Class-Syndrome). American College of Chest Physicians. 7 February 2012. Archived (https://web.archive.org/web/20160603075103/http://www.chestnet.org/News/Press-Releases/2012/02/ACCP-Antithrombotic-and-Economy-Class-Syndrome) from the original on 3 June 2016. Retrieved10 February 2012. \"oral contraceptives, sitting in a window seat, advanced age, andpregnancy increase DVT risk in long-distance travelers\"163. Clarke MJ, Broderick C, Hopewell S, Juszczak E, Eisinga A (April 2021). \"Compressionstockings for preventing deep vein thrombosis in airline passengers\" (https://ora.ox.ac.uk/objects/uuid:5636a717-65b5-4d1e-984b-f8c3d980a0dd/download_file?safe_filename=Clarke_et_al-2016-The_Cochrane_Library.sup-2%2B%25281%2529.pdf&file_format=application%2Fpdf&type_of_work=Journal+article). The Cochrane Database of Systematic Reviews. 2021(4): CD004002. doi 10.1002/14651858.CD004002.pub4 (https://doi.org/10.1002%2F1465185:8.CD004002.pub4) PMC. 8092568. PMID 33878207 (https://pubmed.ncbi.nlm.nih.gov/33878207).164. Galanaud JP, Monreal M, Kahn SR (April 2018). \"Epidemiology of the post-thromboticsyndrome\". Thrombosis Research. 164: 100–09. doi 10.1016/j.thromres.2017.07.026 (https://:doi.org/10.1016%2Fj.thromres.2017.07.026) PMID 28844444 (https://pubmed.ncbi.nlm.nih.g. ov/28844444).
165. Galanaud JP, Righini M, Le Collen L, Douillard A, Robert-Ebadi H, Pontal D, et al. (January2020). \"Long-term risk of postthrombotic syndrome after symptomatic distal deep veinthrombosis: The CACTUS-PTS study\" (https://doi.org/10.1111%2Fjth.14728). Journal ofThrombosis and Haemostasis. 18 (4): 857–64. doi 10.1111/jth.14728 (https://doi.org/10.111:1%2Fjth.14728) PMID 31899848 (https://pubmed.ncbi.nlm.nih.gov/31899848). .166. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al.(November 2014). \"2014 ESC guidelines on the diagnosis and management of acutepulmonary embolism\" (https://doi.org/10.1093%2Feurheartj%2Fehu283). European HeartJournal. 35 (43): 3033–69, 3069a–69k. doi 10.1093/eurheartj/ehu283 (https://doi.org/10.109:3%2Feurheartj%2Fehu283) PMID 25173341 (https://pubmed.ncbi.nlm.nih.gov/25173341). .167. Johannesen CD, Flachs EM, Ebbehøj NE, Marott JL, Jensen GB, Nordestgaard BG, et al.(January 2020). \"Sedentary work and risk of venous thromboembolism\" (https://doi.org/10.5271%2Fsjweh.3841). Scandinavian Journal of Work, Environment & Health. 46 (1): 69–76.doi 10.5271/sjweh.3841 (https://doi.org/10.5271%2Fsjweh.3841) PMID 31385593 (https://pu:. bmed.ncbi.nlm.nih.gov/31385593).168. Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE (January 2016). \"Theeconomic burden of incident venous thromboembolism in the United States: A review ofestimated attributable healthcare costs\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706477). Thrombosis Research. 137: 3–10. doi 10.1016/j.thromres.2015.11.033 (https://doi.org/1:0.1016%2Fj.thromres.2015.11.033) PMC 4706477 (https://www.ncbi.nlm.nih.gov/pmc/article. s/PMC4706477) PMID 26654719 (https://pubmed.ncbi.nlm.nih.gov/26654719). .169. Monagle P, Cuello CA, Augustine C, Bonduel M, Brandão LR, Capman T, et al. (November2018). \"American Society of Hematology 2018 Guidelines for management of venousthromboembolism: treatment of pediatric venous thromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258911). Blood Advances. (22): 3292–316.2doi 10.1182/bloodadvances.2018024786 (https://doi.org/10.1182%2Fbloodadvances.201802:4786) PMC 6258911 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258911). .PMID 30482766 (https://pubmed.ncbi.nlm.nih.gov/30482766).170. Januel JM, Chen G, Ruffieux C, Quan H, Douketis JD, Crowther MA, et al. (January 2012).\"Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip andknee arthroplasty among patients receiving recommended prophylaxis: a systematic review\"(https://doi.org/10.1001%2Fjama.2011.2029). JAMA. 307 (3): 294–303.doi 10.1001/jama.2011.2029 (https://doi.org/10.1001%2Fjama.2011.2029) PMID 22253396:. (https://pubmed.ncbi.nlm.nih.gov/22253396).171. Margaglione M, Grandone E (February 2011). \"Population genetics of venousthromboembolism. A narrative review\". Thrombosis and Haemostasis. 105 (2): 221–31.doi 10.1160/TH10-08-0510 (https://doi.org/10.1160%2FTH10-08-0510) PMID 20941456 (htt:. ps://pubmed.ncbi.nlm.nih.gov/20941456).172. \"Blood types\" (http://www.redcrossblood.org/learn-about-blood/blood-types). American RedCross. Archived (https://web.archive.org/web/20120814050932/http://www.redcrossblood.org/learn-about-blood/blood-types) from the original on 14 August 2012. Retrieved 15 August2012.173. Haskell R (10 January 2018). \"Serena Williams on motherhood, marriage, and making hercomeback\" (https://www.vogue.com/article/serena-williams-vogue-cover-interview-february-2018). Vogue. Retrieved 22 January 2020.174. Golemi I, Salazar Adum JP, Tafur A, Caprini J (August 2019). \"Venous thromboembolismprophylaxis using the Caprini score\". Disease-a-Month. 65 (8): 249–98.doi 10.1016/j.disamonth.2018.12.005 (https://doi.org/10.1016%2Fj.disamonth.2018.12.005):.PMID 30638566 (https://pubmed.ncbi.nlm.nih.gov/30638566).175. Perez AJ (17 February 2016). \"Expert: Chris Bosh, like many, at risk of blood clot recurrence\"(https://www.usatoday.com/story/sports/nba/heat/2016/02/16/chris-bosh-risk-blood-clot-recurrence/80453318/). USA Today. Retrieved 22 January 2020.176. Martin J (4 May 2016). \"Chris Bosh officially out as Heat make playoff push\" (https://www.cnn.com/2016/05/04/sport/chris-bosh-absence-nba-playoffs/index.html). CNN. Retrieved22 January 2020.
177. Moisse K (2 March 2011). \"Serena Williams Hospitalized After Pulmonary Embolism\" (https://abcnews.go.com/Health/Wellness/serena-williams-hospitalized-pulmonary-embolism/story?id=13036965). ABC News. Retrieved 22 January 2020.178. Andrews BL, Friedman Ross L (February 2021). \"Black Women and Babies Matter\". TheAmerican Journal of Bioethics. 21 (2): 93–95. doi 10.1080/15265161.2020.1861384 (https://d:oi.org/10.1080%2F15265161.2020.1861384) PMID 33534674 (https://pubmed.ncbi.nlm.nih.. gov/33534674) S2CID 231803661 (https://api.semanticscholar.org/CorpusID:231803661). .179. Pascarella L, Pappas TN (February 2013). \"Phlebitis, pulmonary emboli and presidentialpolitics: Richard M. Nixon's complicated deep vein thrombosis\" (https://doi.org/10.1177%2F000313481307900222). The American Surgeon. 79 (2): 128–34.doi 10.1177/000313481307900222 (https://doi.org/10.1177%2F000313481307900222):.PMID 23336651 (https://pubmed.ncbi.nlm.nih.gov/23336651).180. Frankel TC (11 September 2016). \"Hillary Clinton has not been quick to share healthinformation\" (https://www.washingtonpost.com/politics/hillary-clinton-has-not-been-quick-to-share-health-information/2016/09/11/822b1b0c-784d-11e6-bd86-b7bbd53d2b5d_story.html).The Washington Post. Retrieved 22 January 2020.181. \"Cheney diagnosed with deep-vein thrombosis\" (https://www.theguardian.com/world/2007/mar/06/usa.dickcheney1). The Guardian. 6 March 2007. Retrieved 22 January 2020.182. Rodriguez D (12 October 2018). \"11 Celebrities Who Battled Deep Vein Thrombosis Risk\" (https://www.everydayhealth.com/pictures/celebrities-who-battled-deep-vein-thrombosis/).Everyday Health. Retrieved 22 January 2020.183. \"Coroner: Rapper Heavy D died of blood clot in lung\" (https://www.cnn.com/2011/12/27/showbiz/heavy-d-autopsy/index.html). CNN. 27 December 2011. Retrieved 22 January 2020.184. \"My husband should be living today\" (https://www.today.com/news/my-husband-should-be-living-today-wbna7074940). TODAY. 3 March 2005. Retrieved 22 January 2020.185. Eliot M (2006). Jimmy Stewart: A Biography. New York: Random House. p. 409. ISBN 978-1400052226.186. Goodman LR (October 2013). \"In search of venous thromboembolism: the first 2913 years\"(https://doi.org/10.2214%2FAJR.13.10604). American Journal of Roentgenology. 201 (4):W576-81. doi 10.2214/AJR.13.10604 (https://doi.org/10.2214%2FAJR.13.10604):.PMID 24059395 (https://pubmed.ncbi.nlm.nih.gov/24059395).187. Galanaud JP, Laroche JP, Righini M (March 2013). \"The history and historical treatments ofdeep vein thrombosis\" (https://doi.org/10.1111%2Fjth.12127). Journal of Thrombosis andHaemostasis. 11 (3): 402–11. doi 10.1111/jth.12127 (https://doi.org/10.1111%2Fjth.12127):.PMID 23297815 (https://pubmed.ncbi.nlm.nih.gov/23297815).188. Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH (December 2010). \"Virchow's contributionto the understanding of thrombosis and cellular biology\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006583). Clinical Medicine & Research. (3–4): 168–72.8doi 10.3121/cmr.2009.866 (https://doi.org/10.3121%2Fcmr.2009.866) PMC 3006583 (https://:. www.ncbi.nlm.nih.gov/pmc/articles/PMC3006583) PMID 20739582 (https://pubmed.ncbi.nl. m.nih.gov/20739582).189. Bagot CN, Arya R (October 2008). \"Virchow and his triad: a question of attribution\" (https://doi.org/10.1111%2Fj.1365-2141.2008.07323.x). British Journal of Haematology. 143 (2): 180–90. doi 10.1111/j.1365-2141.2008.07323.x (https://doi.org/10.1111%2Fj.1365-2141.2008.073:23.x) PMID 18783400 (https://pubmed.ncbi.nlm.nih.gov/18783400). .190. Dalen 2003, p. 3.191. Line BR, Peters TL, Keenan J (January 1997). \"Diagnostic test comparisons in patients withdeep venous thrombosis\" (http://jnm.snmjournals.org/content/38/1/89.full.pdf) (PDF). Journalof Nuclear Medicine. 38 (1): 89–92. PMID 8998158 (https://pubmed.ncbi.nlm.nih.gov/8998158).192. Dalen 2003, p. 2.193. Ornstein C, Jones RG (7 January 2015). \"The drugs that companies promote to doctors arerarely breakthroughs\" (https://www.nytimes.com/2015/01/08/upshot/the-drugs-that-companies-promote-to-doctors-are-rarely-breakthroughs.html). The New York Times.
Classification ICD-10: I80.2 (https://icd.who.int/browse10/2019/en#/I80.2) · ICD-9-CM:453.40 (http://www.icd9data.com/getICD9Code.ashx?icd9=453.40) · MeSH:D020246 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D020246) ·Cited literatureDalen JE (2003). Venous thromboembolism (https://books.google.com/books?id=u-3Fiw7yE5kC&pg=PA1). CRC Press. ISBN 978-0824756451.Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ (February 2012).\"Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: AmericanCollege of Chest Physicians evidence-based clinical practice guidelines\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278060). Chest. 141 (2 Suppl): 7S–47S.doi 10.1378/chest.1412S3 (https://doi.org/10.1378%2Fchest.1412S3) PMC 3278060 (http:. s://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278060) PMID 22315257 (https://pubmed.ncbi.. nlm.nih.gov/22315257).194. Franchini M, Mannucci PM (September 2016). \"Direct oral anticoagulants and venousthromboembolism\" (https://doi.org/10.1183%2F16000617.0025-2016). European RespiratoryReview. 25 (141): 295–302. doi 10.1183/16000617.0025-2016 (https://doi.org/10.1183%2F16:000617.0025-2016) PMID 27581829 (https://pubmed.ncbi.nlm.nih.gov/27581829). .195. Dasta JF, Pilon D, Mody SH, Lopatto J, Laliberté F, Germain G, et al. (February 2015). \"Dailyhospitalization costs in patients with deep vein thrombosis or pulmonary embolism treatedwith anticoagulant therapy\" (https://doi.org/10.1016%2Fj.thromres.2014.11.024). ThrombosisResearch. 135 (2): 303–10. doi 10.1016/j.thromres.2014.11.024 (https://doi.org/10.1016%2F:j.thromres.2014.11.024) PMID 25555319 (https://pubmed.ncbi.nlm.nih.gov/25555319). .196. Ruppert A, Steinle T, Lees M (2011). \"Economic burden of venous thromboembolism: asystematic review\" (https://doi.org/10.3111%2F13696998.2010.546465). Journal of MedicalEconomics. 14 (1): 65–74. doi 10.3111/13696998.2010.546465 (https://doi.org/10.3111%2F1:3696998.2010.546465) PMID 21222564 (https://pubmed.ncbi.nlm.nih.gov/21222564). .197. Dobesh PP (August 2009). \"Economic burden of venous thromboembolism in hospitalizedpatients\". Pharmacotherapy. 29 (8): 943–53. doi 10.1592/phco.29.8.943 (https://doi.org/10.1:592%2Fphco.29.8.943) PMID 19637948 (https://pubmed.ncbi.nlm.nih.gov/19637948). .S2CID 8966676 (https://api.semanticscholar.org/CorpusID:8966676).198. Fernandez MM, Hogue S, Preblick R, Kwong WJ (2015). \"Review of the cost of venousthromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559246).ClinicoEconomics and Outcomes Research. : 451–62. 7doi 10.2147/CEOR.S85635 (https://d:oi.org/10.2147%2FCEOR.S85635) PMC 4559246 (https://www.ncbi.nlm.nih.gov/pmc/article. s/PMC4559246) PMID 26355805 (https://pubmed.ncbi.nlm.nih.gov/26355805). .199. Metz AK, Diaz JA, Obi AT, Wakefield TW, Myers DD, Henke PK (2018). \"Venous thrombosisand post-thrombotic syndrome: from novel biomarkers to biology\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217569). Methodist DeBakey Cardiovascular Journal. 14 (3): 173–81.doi 10.14797/mdcj-14-3-173 (https://doi.org/10.14797%2Fmdcj-14-3-173): (inactive 31 May2021). PMC 6217569 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217569).PMID 30410646 (https://pubmed.ncbi.nlm.nih.gov/30410646).D
DiseasesDB: 3498(http://www.diseasesdatabase.com/ddb3498.htm)ExternalresourcesMedlinePlus:000156 (https://www.nlm.nih.gov/medlineplus/ency/article/000156.htm) ·eMedicine:med/2785 (https://emedicine.medscape.com/med/2785-overview) · PatientUK: Deep veinthrombosis (https://patient.info/doctor/deep-vein-thrombosis-pro)Retrieved from \"https://en.wikipedia.org/w/index.php?title=Deep_vein_thrombosis&oldid=1043588002\"This page was last edited on 10 September 2021, at 21:37 (UTC).Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By usingthis site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the WikimediaFoundation, Inc., a non-profit organization.
Disseminated intravascularcoagulationOther namesDisseminated intravascularcoagulopathy, consumptivecoagulopathy, defibrinationsyndrome[1]Micrograph showing acute thromboticmicroangiopathy due to DIC in a kidney biopsy.A clot is present in the hilum of the glomerulus(center of image).SpecialtyHematologySymptomsChest pain, shortness ofbreath, leg pain, problemsspeaking, problems movingpart of the body, bleeding[1]ComplicationsOrgan failure[2]TypesAcute, chronic[1]CausesSepsis, surgery, major trauma,cancer, complications ofDisseminated intravascular coagulationDisseminated intravascular coagulation(DIC) is a condition in which blood clots formthroughout the body, blocking small bloodvessels. Symptoms may include chest pain,[1]shortness of breath, leg pain, problems speaking,or problems moving parts of the body. As[1]clotting factors and platelets are used up, bleedingmay occur. This may include blood in the urine,[1]blood in the stool, or bleeding into the skin.[1]Complications may include organ failure.[2]Relatively common causes include sepsis, surgery,major trauma, cancer, and complications ofpregnancy. Less common causes include snake[1]bites, frostbite, and burns. There are two main[1]types: acute (rapid onset) and chronic (slowonset). Diagnosis is typically based on blood[1]tests.[2] Findings may include low platelets, lowfibrinogen, high INR, or high D-dimer.[2]Treatment is mainly directed towards theunderlying condition.[2][3] Other measures mayinclude giving platelets, cryoprecipitate, or freshfrozen plasma.[2] Evidence to support thesetreatments, however, is poor.[2] Heparin may beuseful in the slowly developing form.[2] About 1%of people admitted to hospital are affected by thecondition.[4] In those with sepsis, rates arebetween 20% and 50%.[4] The risk of death amongthose affected varies from 20 to 50%.[4]Signs and symptomsCausesPathophysiologyDiagnosisTreatmentPrognosisEpidemiologyReferencesContents
pregnancy, snake bites,frostbite, burns[1]DiagnosticmethodBlood tests[2]DifferentialdiagnosisThrombotic thrombocytopenicpurpura, hemolytic-uremicsyndrome[1]TreatmentDirected at the underlyingcondition[3]MedicationPlatelets, cryoprecipitate,fresh frozen plasma, heparin[2]Prognosis20–50% risk of death[4]Frequency1% of people admitted tohospital[4]The coagulation cascade of secondary hemostasis.In DIC, the underlying cause usually leads tosymptoms and signs, and DIC is discovered onlaboratory testing. The onset of DIC can besudden, as in endotoxic shock or amniotic fluidembolism, or it may be insidious and chronic, as incancer. DIC can lead to multiorgan failure andwidespread bleeding.[5]DIC can occur in the followingconditions:[5][6][7][8]Cancer: solid tumors and blood cancers(particularly acute promyelocytic leukemia)Complications of pregnancy: abruptio placentae, pre-eclampsia or eclampsia, amniotic fluidembolism, retained intrauterine fetal demise, septic abortion, postpartum hemorrhageMassive tissue injury: trauma, burn, hyperthermia, rhabdomyolysis, surgeryInfection: bacterial (Gram-negative or Gram-positive), viral, fungal, or protozoanTransfusion reaction: ABO incompatibilityAllergic or toxic reaction: snake venomHemangioma: Kasabach–Merritt syndromeAortic aneurysmLiver disease, HELLP syndrome, thrombotic thrombocytopenic purpura, hemolytic uremicsyndrome, and malignant hypertension may mimic DIC but originate via other pathways.[9]Under homeostatic conditions, thebody is maintained in a finelytuned balance of coagulation andfibrinolysis. The activation of thecoagulation cascade yieldsthrombin that converts fibrinogento fibrin; the stable fibrin clotbeing the final product ofhemostasis. The fibrinolytic systemthen functions to break downfibrinogen and fibrin. Activation ofthe fibrinolytic system generatesplasmin (in the presence ofthrombin), which is responsible forthe lysis of fibrin clots. Thebreakdown of fibrinogen and fibrinresults in polypeptides called fibrindegradation products (FDPs) orSigns and symptomsCausesPathophysiology
fibrin split products (FSPs). In a state of homeostasis, the presence of plasmin is critical, as it isthe central proteolytic enzyme of coagulation and is also necessary for the breakdown of clots, orfibrinolysis.In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result iswidespread clotting with resultant bleeding. Regardless of the triggering event of DIC, onceinitiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC isthe release of a transmembrane glycoprotein called tissue factor (TF). TF is present on thesurface of many cell types (including endothelial cells, macrophages, and monocytes) and is notnormally in contact with the general circulation, but is exposed to the circulation after vasculardamage. For example, TF is released in response to exposure to cytokines (particularlyinterleukin 1), tumor necrosis factor, and endotoxin.[10] This plays a major role in thedevelopment of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, andplacenta. This helps to explain why DIC readily develops in patients with extensive trauma. Uponexposure to blood and platelets, TF binds with activated factor VIIa (normally present in traceamounts in the blood), forming the extrinsic tenase complex. This complex further activatesfactor IX and X to IXa and Xa, respectively, leading to the common coagulation pathway and thesubsequent formation of thrombin and fibrin.[7]The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC. Inacute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyteprecursors, resulting in the release of large amounts of proteolytic enzymes from their storagegranules, causing microvascular damage. Other malignancies may enhance the expression ofvarious oncogenes that result in the release of TF and plasminogen activator inhibitor-1 (PAI-1),which prevents fibrinolysis.[11]Excess circulating thrombin results from the excess activation of the coagulation cascade. Theexcess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in thecirculation. These excess clots trap platelets to become larger clots, which leads to microvascularand macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels,and in the organs is what leads to the ischemia, impaired organ perfusion, and end-organdamage that occurs with DIC.[12][13]Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permitmore clotting so that a positive feedback loop develops in which increased clotting leads to moreclotting. At the same time, thrombocytopenia occurs and this has been attributed to theentrapment and consumption of platelets. Clotting factors are consumed in the development ofmultiple clots, which contributes to the bleeding seen with DIC.[14][15]Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin,resulting in fibrinolysis. The breakdown of clots results in an excess of FDPs, which havepowerful anticoagulant properties, contributing to hemorrhage. The excess plasmin alsoactivates the complement and kinin systems. Activation of these systems leads to many of theclinical symptoms that patients experiencing DIC exhibits, such as shock, hypotension, andincreased vascular permeability. The acute form of DIC is considered an extreme expression ofthe intravascular coagulation process with a complete breakdown of the normal homeostaticboundaries. DIC is associated with a poor prognosis and a high mortality rate.[16][17]There has been a recent challenge however to the basic assumptions and interpretations of thepathophysiology of DIC. A study of sepsis and DIC in animal models has shown that a highlyexpressed receptor on the surface of hepatocytes, termed the Ashwell-Morell receptor, isresponsible for thrombocytopenia in bacteremia and sepsis due to Streptococcus pneumoniae(SPN) and possibly other pathogens. The thrombocytopenia observed in SPN sepsis was not dueto increased consumption of coagulation factors such as platelets, but instead was the result of
Blood film showing red blood cell fragments(schistocytes)this receptor's activity enabling hepatocytes to ingest and rapidly clear platelets fromcirculation.[18] By removing prothrombotic components before they participate in thecoagulopathy of DIC, the Ashwell-Morell receptor lessens the severity of DIC, reducingthrombosis and tissue necrosis, and promoting survival. The hemorrhage observed in DIC andamong some tissues lacking this receptor may therefore be secondary to increased thrombosiswith loss of the mechanical vascular barrier.[19][20]Activation of the intrinsic and extrinsic coagulation pathways causes excess thrombus formationin the blood vessels. Consumption of coagulation factors due to extensive coagulation in turncauses bleeding.[21][22]The diagnosis of DIC is not made on a singlelaboratory value, but rather the constellation oflaboratory markers and a consistent history of anillness known to cause DIC. Laboratory markersconsistent with DIC include:[3][7][23]Characteristic history (this is importantbecause severe liver disease can essentiallyhave the same laboratory findings as DIC)Prolongation of the prothrombin time (PT) andthe activated partial thromboplastin time(aPTT) reflect the underlying consumption andimpaired synthesis of the coagulation cascade.Fibrinogen level was initially thought to beuseful in the diagnosis of DIC but because it isan acute phase reactant, it will be elevated dueto the underlying inflammatory condition. Therefore, a normal (or even elevated) level canoccur in over 57% of cases. A low level, however, is more consistent with the consumptiveprocess of DIC.A rapidly declining platelet countHigh levels of fibrin degradation products, including D-dimer, are found owing to the intensefibrinolytic activity stimulated by the presence of fibrin in the circulation.The peripheral blood smear may show fragmented red blood cells (known as schistocytes)due to shear stress from thrombi. However, this finding is neither sensitive nor specific forDICA diagnostic algorithm has been proposed by the International Society of Thrombosis andHaemostasis. This algorithm appears to be 91% sensitive and 97% specific for the diagnosis ofovert DIC. A score of 5 or higher is compatible with DIC and it is recommended that the score isrepeated daily, while a score below 5 is suggestive but not affirmative for DIC and it isrecommended that it is repeated only occasionally:[23][24] It has been recommended that ascoring system be used in the diagnosis and management of DIC in terms of improvingoutcome.[25]Presence of an underlying disorder known to be associated with DIC (no=0, yes=2)Global coagulation resultsPlatelet count (> 100k = 0, < 100k = 1, < 50k = 2)Fibrin degradation products such as D-Dimer (no increase = 0, moderate increase = 2,strong increase = 3)Diagnosis
Prolonged prothrombin time (< 3 sec = 0, > 3 sec = 1, > 6 sec = 2)Fibrinogen level (> 1.0g/L = 0; < 1.0g/L = 1[26])Treatment of DIC is centered around treating the underlying condition. Transfusions of plateletsor fresh frozen plasma can be considered in cases of significant bleeding, or those with a plannedinvasive procedure. The target goal of such transfusion depends on the clinical situation.Cryoprecipitate can be considered in those with a low fibrinogen level. Treatment of thrombosiswith anticoagulants such as heparin is rarely used due to the risk of bleeding.Recombinant human activated protein C was previously recommended in those with severesepsis and DIC, but drotrecogin alfa has been shown to confer no benefit and was withdrawnfrom the market in 2011.[27]Recombinant factor VII has been proposed as a \"last resort\" in those with severe hemorrhagedue to obstetric or other causes, but conclusions about its use are still insufficient.[28]Prognosis varies depending on the underlying disorder, and the extent of the intravascularthrombosis (clotting). The prognosis for those with DIC, regardless of cause, is often grim:between 20% and 50% of patients will die.[29] DIC with sepsis (infection) has a significantlyhigher rate of death than DIC associated with trauma.[29]DIC is observed in approximately 1% of academic hospital admissions.[30] DIC occurs at higherrates in people with bacterial sepsis (83%),[31] severe trauma (31%),[32] and cancer (6.8%).[33]1. \"Disseminated Intravascular Coagulation | NHLBI, NIH\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). www.nhlbi.nih.gov. Retrieved 20 December2017.2. \"Disseminated Intravascular Coagulation (DIC) - Hematology and Oncology\" (https://www.merckmanuals.com/en-ca/professional/hematology-and-oncology/coagulation-disorders/disseminated-intravascular-coagulation-dic). Merck Manuals Professional Edition. September 2016.Retrieved 20 December 2017.3. Levi, M (2007). \"Disseminated Intravascular Coagulation\". Critical Care Medicine. 35 (9):2191–2195. doi 10.1097/01.CCM.0000281468.94108.4B (https://doi.org/10.1097%2F01.CC:M.0000281468.94108.4B) PMID 17855836 (https://pubmed.ncbi.nlm.nih.gov/17855836). .S2CID 7158989 (https://api.semanticscholar.org/CorpusID:7158989).4. Gando, Satoshi; Levi, Marcel; Toh, Cheng-Hock (2 June 2016). \"Disseminated intravascularcoagulation\". Nature Reviews Disease Primers. : 16037. 2doi 10.1038/nrdp.2016.37 (https://:doi.org/10.1038%2Fnrdp.2016.37) PMID 27250996 (https://pubmed.ncbi.nlm.nih.gov/27250. 996) S2CID 4059451 (https://api.semanticscholar.org/CorpusID:4059451). .5. Robbins, Stanley L.; Cotran, Ramzi S.; Kumar, Vinay; Collins, Tucker (1999). Robbins'Pathologic Basis of Disease (6 ed.). Philadelphia: Saunders. ISBN 0-7216-7335-X.TreatmentPrognosisEpidemiologyReferences
6. Davidson's Principles and Practice of Medicine (19 ed.). Churchill Livingstone. 2002. ISBN 0-443-07036-9.7. Haematology: Basic Principles and Practice (6 ed.). Elsevier Saunders. 2012. ISBN 978-1437729283.8. Clark, Michael; Kumar, Parveen J. (1998). Clinical Medicine: A Textbook for MedicalStudents and Doctors (4 ed.). Philadelphia: W.B. Saunders. ISBN 0-7020-2458-9.9. \"Disseminated Intravascular Coagulation\" (https://www.lecturio.com/concepts/disseminated-intravascular-coagulation/). The Lecturio Medical Concept Library. Retrieved 12 July 2021.10. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins BasicPathology (8th ed.). Saunders Elsevier. pp. 469-471 ISBN 978-1-4160-2973-111. Rak J, Yu JL, Luyendyk J, Mackman N (2006). \"Oncogenes, trousseau syndrome, andcancer-related changes in the coagulome of mice and humans\" (http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17108099). Cancer Res. 66 (22): 10643–6.doi 10.1158/0008-5472.CAN-06-2350 (https://doi.org/10.1158%2F0008-5472.CAN-06-2350):.PMID 17108099 (https://pubmed.ncbi.nlm.nih.gov/17108099).12. \"Disseminated Intravascular Coagulation\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). National Heart, Lung And Blood Institute. Retrieved 12 July2021.13. \"Disseminated Intravascular Coagulation (DIC)\" (https://emedicine.medscape.com/article/199627-overview). Medscape. Retrieved 12 July 2021.14. \"Disseminated Intravascular Coagulation\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). National Heart, Lung And Blood Institute. Retrieved 12 July2021.15. \"Disseminated Intravascular Coagulation (DIC)\" (https://emedicine.medscape.com/article/199627-overview). Medscape. Retrieved 12 July 2021.16. \"Disseminated Intravascular Coagulation\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). National Heart, Lung And Blood Institute. Retrieved 12 July2021.17. \"Disseminated Intravascular Coagulation (DIC)\" (https://emedicine.medscape.com/article/199627-overview). Medscape. Retrieved 12 July 2021.18. Grewal, PK; Uchiyama, S; Ditto, D; Varki, N; Le, DT; Nizet, V; Marth, JD (June 2008). \"TheAshwell receptor mitigates the lethal coagulopathy of sepsis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853759). Nature Medicine. 14 (6): 648–55. doi 10.1038/nm1760 (https://do:i.org/10.1038%2Fnm1760) PMC 2853759 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2. 853759) PMID 18488037 (https://pubmed.ncbi.nlm.nih.gov/18488037). .19. \"Disseminated Intravascular Coagulation\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). National Heart, Lung And Blood Institute. Retrieved 12 July2021.20. \"Disseminated Intravascular Coagulation (DIC)\" (https://emedicine.medscape.com/article/199627-overview). Medscape. Retrieved 12 July 2021.21. \"Disseminated Intravascular Coagulation\" (https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation). National Heart, Lung And Blood Institute. Retrieved 12 July2021.22. \"Disseminated Intravascular Coagulation (DIC)\" (https://emedicine.medscape.com/article/199627-overview). Medscape. Retrieved 12 July 2021.23. Levi, M; Toh, C-H; et al. (2009). \"Guidelines for the diagnosis and management ofdisseminated intravascular coagulation\" (https://doi.org/10.1111%2Fj.1365-2141.2009.07600.x). British Journal of Haematology. 145 (5): 24–33. doi 10.1111/j.1365-2141.2009.07600.x (ht:tps://doi.org/10.1111%2Fj.1365-2141.2009.07600.x) PMID 19222477 (https://pubmed.ncbi.nl. m.nih.gov/19222477).
Classification ICD-10: D65 (https://icd.who.int/browse10/2019/en#/D65) · ICD-9-CM:286.6 (http://www.icd9data.com/getICD9Code.ashx?icd9=286.6) · MeSH:24. Taylor, F; Toh, C-h; et al. (2001). \"Towards Definition, Clinical and Laboratory Criteria, and aScoring System for Disseminated Intravascular Coagulation\". Thrombosis and Haemostasis.86 (5): 1327–30. doi 10.1055/s-0037-1616068 (https://doi.org/10.1055%2Fs-0037-1616068):.PMID 11816725 (https://pubmed.ncbi.nlm.nih.gov/11816725) S2CID 39696424 (https://api.s. emanticscholar.org/CorpusID:39696424).25. Gando, S (2012). \"The Utility of a Diagnostic Scoring System for Disseminated IntravascularCoagulation\". Critical Care Clinics. 28 (3): 378–88. doi 10.1016/j.ccc.2012.04.004 (https://doi.:org/10.1016%2Fj.ccc.2012.04.004) PMID 22713612 (https://pubmed.ncbi.nlm.nih.gov/22713. 612).26. Levi, M.; Toh, C. H.; Thachil, J.; Watson, H. G. (2009). \"Guidelines for the diagnosis andmanagement of disseminated intravascular coagulation\" (https://doi.org/10.1111%2Fj.1365-2141.2009.07600.x). British Journal of Haematology. 145 (1): 24–33. doi 10.1111/j.1365-:2141.2009.07600.x (https://doi.org/10.1111%2Fj.1365-2141.2009.07600.x) PMID 19222477. (https://pubmed.ncbi.nlm.nih.gov/19222477).27. Armstrong, Drew (October 25, 2011). \"Lilly Pulls Xigris Off Markets After Sepsis Drug FailsStudy\" (https://www.bloomberg.com/news/articles/2011-10-25/lilly-pulls-xigris-from-markets-after-sepsis-drug-fails-study). Bloomberg News. Retrieved June 26, 2020.28. Franchini, M; Manzato, F; Salvagno GL; et al. (2007). \"Potential role of recombinant activatedfactor VII for the treatment of severe bleeding associated with disseminated intravascularcoagulation: a systematic review\". Blood Coagul Fibrinolysis. 18 (7): 589–93.doi 10.1097/MBC.0b013e32822d2a3c:(https://doi.org/10.1097%2FMBC.0b013e32822d2a3c) PMID 17890943 (https://pubmed.ncb. i.nlm.nih.gov/17890943) S2CID 37247533 (https://api.semanticscholar.org/CorpusID:372475. 33).29. Becker, Joseph U and Charles R Wira. Disseminated intravascular coagulation (http://emedicine.medscape.com/article/779097-overview) at eMedicine, 10 September 200930. Matsuda, T (Jan–Feb 1996). \"Clinical aspects of DIC--disseminated intravascularcoagulation\". Pol J Pharmacol. 48 (1): 73–5. PMID 9112631 (https://pubmed.ncbi.nlm.nih.gov/9112631).31. Smith, OP (1997). \"Use of protein-C concentrate, heparin, and haemodiafiltration inmeningococcus-induced purpura fulminans\". Lancet. 350 (9091): 1590–1593.doi 10.1016/s0140-6736(97)06356-3 (https://doi.org/10.1016%2Fs0140-6736%2897%29063:56-3) PMID 9393338 (https://pubmed.ncbi.nlm.nih.gov/9393338) S2CID 38614343 (https://a. . pi.semanticscholar.org/CorpusID:38614343).32. Gando, S (1999). \"Disseminated intravascular coagulation and sustained systemicinflammatory response syndrome predict organ dysfunctions after trauma: application ofclinical decision analysis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1191617). AnnSurg. 229 (1): 121–127. doi 10.1097/00000658-199901000-00016 (https://doi.org/10.1097%:2F00000658-199901000-00016) PMC 1191617 (https://www.ncbi.nlm.nih.gov/pmc/articles/P. MC1191617) PMID 9923809 (https://pubmed.ncbi.nlm.nih.gov/9923809). .33. Sallah, S (2001). \"Disseminated intravascular coagulation in solid tumors: clinical andpathologic study\". Thromb. Haemost. 86 (3): 828–833. doi 10.1055/s-0037-1616139 (https://:doi.org/10.1055%2Fs-0037-1616139) PMID 11583315 (https://pubmed.ncbi.nlm.nih.gov/115. 83315).D
D004211 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D004211) ·DiseasesDB: 3765(http://www.diseasesdatabase.com/ddb3765.htm)ExternalresourcesMedlinePlus:000573 (https://www.nlm.nih.gov/medlineplus/ency/article/000573.htm) ·eMedicine:med/577 (https://emedicine.medscape.com/med/577-overview) emerg/150 (http://www.emedicine.com/emerg/topic150.htm#)Retrieved from \"https://en.wikipedia.org/w/index.php?title=Disseminated_intravascular_coagulation&oldid=1034931852\"This page was last edited on 22 July 2021, at 16:55 (UTC).Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By usingthis site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the WikimediaFoundation, Inc., a non-profit organization.
EmbolismMicrograph of embolic material in the artery of akidney. The kidney was surgically removedbecause of cancer. H&E stain.SpecialtyVascular surgeryEmbolismAn embolism is the lodging of an embolus, ablockage-causing piece of material, inside a bloodvessel. The embolus may be a blood clot[1](thrombus), a fat globule (fat embolism), a bubbleof air or other gas (gas embolism), amniotic fluid(amniotic fluid embolism), or foreign material. Anembolism can cause partial or total blockage ofblood flow in the affected vessel.[2] Such ablockage (a vascular occlusion) may affect a part ofthe body distant from the origin of the embolus.An embolism in which the embolus is a piece ofthrombus is called a thromboembolism.An embolism is usually a pathological event, i.e.,accompanying illness or injury. Sometimes it iscreated intentionally for a therapeutic reason,such as to stop bleeding or to kill a canceroustumor by stopping its blood supply. Such therapyis called embolization.ClassificationArterialVenousParadoxical (venous to arterial)DirectionEtymologySee alsoReferencesExternal linksThere are different types of embolism, some of which are listed below.Embolism can be classified based on where it enters the circulation, either in arteries or in veins.Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distalpart of the systemic circulation. Sometimes, multiple classifications apply; for instance apulmonary embolism is classified as an arterial embolism as well,[3] in the sense that the clotfollows the pulmonary artery carrying deoxygenated blood away from the heart. However,pulmonary embolism is generally classified as a form of venous embolism, because the embolusforms in veins, e.g. deep vein thrombosis.ContentsClassification
3D Medical Animation still shotshowing Pulmonary EmbolismArterial embolism can cause occlusion in any part of the body. It is a major cause of infarction(tissue death from blockage of the blood supply).[4]An embolus lodging in the brain from either the heart or a carotid artery will most likely be thecause of a stroke due to ischemia.An arterial embolus might originate in the heart (from a thrombus in the left atrium, followingatrial fibrillation or be a septic embolus resulting from endocarditis). Emboli of cardiac origin arefrequently encountered in clinical practice. Thrombus formation within the atrium occurs mainlyin patients with mitral valve disease, and especially in those with mitral valve stenosis(narrowing), with atrial fibrillation (AF). In the absence of AF, pure mitral regurgitation has alow incidence of thromboembolism.The risk of emboli forming in AF depends on other risk factors such as age, hypertension,diabetes, recent heart failure, or previous stroke. Thrombus formation can also take place withinthe ventricles, and it occurs in approximately 30% of anterior-wall myocardial infarctions,compared with only 5% of inferior ones. Some other risk factors are poor ejection fraction(<35%), size of infarct, and the presence of AF. In the first three months after infarction, left-ventricle aneurysms have a 10% risk of emboli forming.Patients with prosthetic valves also carry a significant increase in risk of thromboembolism. Riskvaries, based on the valve type (bioprosthetic or mechanical); the position (mitral or aortic); andthe presence of other factors such as AF, left-ventricular dysfunction, and previous emboli.Emboli often have more serious consequences when they occur in the so-called \"end circulation\":areas of the body that have no redundant blood supply, such as the brain and heart.Assuming a normal circulation, an embolus formed in asystemic vein will always impact in the lungs, after passingthrough the right side of the heart. This will form apulmonary embolism that will result in a blockage of themain artery of the lung and can be a complication of deep-vein thrombosis. The most common sites of origin ofpulmonary emboli are the femoral veins. The deep veins ofthe calf are the most common sites of actual thrombi.In paradoxical embolism, also known as crossed embolism, an embolus from the veins crosses tothe arterial blood system. This is generally found only with heart problems such as septal defects(holes in the cardiac septum) between the atria or ventricles. The most common suchabnormality is patent foramen ovale, occurring in about 25% of the adult population, but herethe defect functions as a valve which is normally closed, because pressure is slightly higher in theleft side of the heart. Sometimes, for example if a patient coughs just when an embolus ispassing, it might cross to the arterial system.ArterialVenousParadoxical (venous to arterial)Direction
Classification ICD-10: I74 (https://icd.who.int/browse10/2019/en#/I74),I82 (https://icd.who.int/browse10/2019/en#/I82), O88 (https://icd.who.int/browse10/2019/en#/O88), T79.0 (https://icd.who.int/browse10/2019/en#/T79.0)-T79.1 (https://icd.who.int/browse10/2019/en#/T79.1) ·ICD-9-CM: 444.9 (http://www.icd9data.com/getICD9Code.aThe direction of the embolus can be one of two types:AnterogradeRetrogradeIn anterograde embolism, the movement of emboli is in the direction of blood flow. In retrogradeembolism, the emboli move in opposition to the blood flow direction; this is usually significantonly in blood vessels with low pressure (veins) or with emboli of high weight.The word embolism comes from the Greek μβολισμός, meaning \"interpressure\".ἐEmbolectomy1. Dorland's (2012). Dowland's Illustrated Medical Dictionary (32nd ed.). Elsevier. p. 606.ISBN 978-1-4160-6257-8.2. Britannica Concise Encyclopedia 20073. MedlinePlus > Arterial embolism (https://www.nlm.nih.gov/medlineplus/ency/article/001102.htm) Sean O. Stitham, MD and David C. Dugdale III, MD. Also reviewed by David Zieve, MD.Reviewed last on: 5/8/2008. Alternative link: [1] (https://web.archive.org/web/20070220214959/http://www.umm.edu/ency/article/001102.htm)4. MDGuidelines > Arterial Embolism And Thrombosis (http://www.mdguidelines.com/arterial-embolism-and-thrombosis) From The Medical Disability Advisor by Presley Reed, MD.Retrieved on April 30, 2010MR of Fat Embolism (https://web.archive.org/web/20120309144010/http://rad.usuhs.edu/medpix/tf_case.html?pt_id=10480&quiz=no) Brain Injury from Fat EmbolismEtymologySee alsoReferencesExternal linksD
shx?icd9=444.9) ·MeSH: D004617 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D004617) ·DiseasesDB:18165 (http://www.diseasesdatabase.com/ddb18165.htm) ·SNOMED CT:414086009 (http://snomed.info/id/414086009)Retrieved from \"https://en.wikipedia.org/w/index.php?title=Embolism&oldid=1040567100\"This page was last edited on 25 August 2021, at 09:53 (UTC).Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By usingthis site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the WikimediaFoundation, Inc., a non-profit organization.
Immune thrombocytopenic purpuraOthernamesIdiopathic thrombocytopenicpurpura, idiopathic immunethrombocytopenia, primary immunethrombocytopenia, idiopathicthrombocytopenic purpura, primaryimmune thrombocytopenic purpura,autoimmune thrombocytopenicpurpuraPetechiae, or small bruise-like markings, mayoccur in ITPSpecialtyHematology, general surgeryImmune thrombocytopenic purpuraImmune thrombocytopenic purpura ITP (),also known as idiopathic thrombocytopenicpurpura or immune thrombocytopenia, is atype of thrombocytopenic purpura defined as anisolated low platelet count with a normal bonemarrow in the absence of other causes of lowplatelets. It causes a characteristic red or purple[1]bruise-like rash and an increased tendency tobleed. Two distinct clinical syndromes manifest asan acute condition in children and a chroniccondition in adults. The acute form often followsan infection and spontaneously resolves withintwo months. Chronic immune thrombocytopeniapersists longer than six months with a specificcause being unknown.ITP is an autoimmune disease with antibodiesdetectable against several platelet surfacestructures.ITP is diagnosed by identifying a low plateletcount on a complete blood count (a common bloodtest). However, since the diagnosis depends on theexclusion of other causes of a low platelet count,additional investigations (such as a bone marrowbiopsy) may be necessary in some cases.In mild cases, only careful observation may berequired but very low counts or significantbleeding may prompt treatment with corticosteroids, intravenous immunoglobulin, anti-Dimmunoglobulin, or immunosuppressive medications. Refractory ITP (not responsive toconventional treatment or constant relapsing after splenectomy) requires treatment to reducethe risk of clinically significant bleeding.[2] Platelet transfusions may be used in severe cases withvery low platelet counts in people who are bleeding. Sometimes the body may compensate bymaking abnormally large platelets.Signs and symptomsPathogenesisDiagnosisTreatmentSteroidsAnti-DSteroid-sparing agentsContents
Intravenous immunoglobulinThrombopoietin receptor agonistsSurgeryPlatelet transfusionH. pylori eradicationOther agentsPrognosisEpidemiologyPregnancyHistoryReferencesExternal linksSigns include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises),especially on the extremities, bleeding from the nostrils and/or gums, and menorrhagia(excessive menstrual bleeding), any of which may occur if the platelet count is below 20,000 perμl.[3] A very low count (<10,000 per μl) may result in the spontaneous formation of hematomas(blood masses) in the mouth or on other mucous membranes. Bleeding time from minorlacerations or abrasions is usually prolonged.Serious and possibly fatal complications due to extremely low counts (<5,000 per μl) includesubarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lowergastrointestinal bleeding or other internal bleeding. An ITP patient with an extremely low countis vulnerable to internal bleeding caused by blunt abdominal trauma, as might be experienced ina motor vehicle crash. These complications are not likely when the platelet count is above 20,000per μl.[4]Petechiae on the Orallower extremitiespetechiae/purpura - tongue in a person lower lower lipPetechia on the Petechia with platelets of 3 person with plateletsdue to ITPof theleg in aof 3 due to ITPSigns and symptomsPathogenesis
Blood film showing giant platelets -arrows - in a person with ITP(Giemsa stain)In approximately 60 percent of cases, antibodies against platelets can be detected.[5] Most oftenthese antibodies are against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and are of theimmunoglobulin G (IgG) type. The Harrington–Hollingsworth experiment established theimmune pathogenesis of ITP.[6]The coating of platelets with IgG renders them susceptible to opsonization and phagocytosis bysplenic macrophages, as well by Kupffer cells in the liver. The IgG autoantibodies are alsothought to damage megakaryocytes, the precursor cells to platelets, although this is believed tocontribute only slightly to the decrease in platelet numbers. Recent research now indicates thatimpaired production of the glycoprotein hormone thrombopoietin, which is the stimulant forplatelet production, may be a contributing factor to the reduction in circulating platelets. Thisobservation has led to the development of a class of ITP-targeted medications referred to asthrombopoietin receptor agonists.[7]The stimulus for auto-antibody production in ITP is probably abnormal T cell activity.[8][9][10]Preliminary findings suggest that these T cells can be influenced by medications that target Bcells, such as rituximab.[11]The diagnosis of ITP is a process of exclusion. First, it has tobe determined that there are no blood abnormalities otherthan a low platelet count, and no physical signs other thanbleeding. Then, secondary causes (5–10 percent ofsuspected ITP cases) should be excluded. Such secondarycauses include leukemia, medications (e.g., quinine,heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C,congenital causes, antiphospholipid syndrome, vonWillebrand factor deficiency, onyalai and others.[3][12] Allpatients with presumed ITP should be tested for HIV andhepatitis C virus, as platelet counts may be corrected bytreating the underlying disease. In approximately 2.7 to 5percent of cases, autoimmune hemolytic anemia and ITPcoexist, a condition referred to as Evans syndrome.[13][14]Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for thethrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use ofbleeding time in diagnosis is discouraged by the American Society of Hematology practiceguidelines[15] and a normal bleeding time does not exclude a platelet disorder.[16]Bone marrow examination may be performed on patients over the age of 60 and those who donot respond to treatment, or when the diagnosis is in doubt.[12] On examination of the marrow,an increase in the production of megakaryocytes may be observed and may help in establishing adiagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, asthere is disagreement on whether the 80 percent specificity of this test is sufficient to beclinically useful.[12]DiagnosisTreatment
With rare exceptions, there is usually no need to treat based on platelet counts. Many olderrecommendations suggested a certain platelet count threshold (usually somewhere below 20.0/µl) as an indication for hospitalization or treatment. Current guidelines recommend treatmentonly in cases of significant bleeding. Treatment recommendations sometimes differ for adult andpediatric ITP.[17]Initial treatment usually consists of the administration of corticosteroids, a group of medicationsthat suppress the immune system. The dose and mode of administration is determined byplatelet count and whether there is active bleeding: in urgent situations, infusions ofdexamethasone or methylprednisolone may be used, while oral prednisone or prednisolone maysuffice in less severe cases. Once the platelet count has improved, the dose of steroid is graduallyreduced while the possibility of relapse is monitored. 60–90 percent will experience a relapseduring dose reduction or cessation.[12][18] Long-term steroids are avoided if possible because ofpotential side-effects that include osteoporosis, diabetes and cataracts.[19]Another option, suitable for Rh-positive patients with functional spleens is intravenousadministration of Rho(D) immune globulin [Human; Anti-D]. The mechanism of action of anti-D is not fully understood. However, following administration, anti-D-coated red blood cellcomplexes saturate Fcγ receptor sites on macrophages, resulting in preferential destruction ofred blood cells (RBCs), therefore sparing antibody-coated platelets. There are two anti-Dproducts indicated for use in patients with ITP: WinRho SDF and Rhophylac. The most commonadverse reactions are headache (15%), nausea/vomiting (12%) chills (<2%) and fever (1%).There is increasing use of immunosuppressants such as mycophenolate mofetil and azathioprinebecause of their effectiveness. In chronic refractory cases, where immune pathogenesis has beenconfirmed,[20] the off-label use of the vinca alkaloid[21][22][23] and chemotherapy agentvincristine may be attempted.[24][25] However, vincristine has significant side effects[26] and itsuse in treating ITP must be approached with caution, especially in children.Intravenous immunoglobulin (IVIg) may be infused in some cases in order to decrease the rate atwhich macrophages consume antibody-tagged platelets. However, while sometimes effective, itis costly and produces improvement that generally lasts less than a month. Nevertheless, in thecase of an ITP patient already scheduled for surgery who has a dangerously low platelet countand has experienced a poor response to other treatments, IVIg can rapidly increase plateletcounts, and can also help reduce the risk of major bleeding by transiently increasing plateletcounts.SteroidsAnti-DSteroid-sparing agentsIntravenous immunoglobulinThrombopoietin receptor agonists
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet productionin the bone marrow. In this, they differ from the previously discussed agents that act byattempting to curtail platelet destruction.[27] Two such products are currently available:Romiplostim (trade name Nplate) is a thrombopoiesis stimulating Fc-peptide fusion protein(peptibody) that is administered by subcutaneous injection. Designated an orphan drug in2003 under United States law, clinical trials demonstrated romiplostim to be effective intreating chronic ITP, especially in relapsed post-splenectomy patients.[28][29] Romiplostimwas approved by the United States Food and Drug Administration (FDA) for long-termtreatment of adult chronic ITP on August 22, 2008.[30]Eltrombopag (trade name Promacta in the USA, Revolade in the EU) is an orally-administered agent with an effect similar to that of romiplostim. It too has beendemonstrated to increase platelet counts and decrease bleeding in a dose-dependentmanner.[31] Developed by GlaxoSmithKline and also designated an orphan drug by the FDA,Promacta was approved by the FDA on November 20, 2008.[32]Thrombopoietin receptor agonists exhibited the greatest success so far in treating patients withrefractory ITP.[33]Side effects of thrombopoietin receptor agonists include headache, joint or muscle pain,dizziness, nausea or vomiting, and an increased risk of blood clots.[27]Splenectomy (removal of the spleen) may be considered in patients who are either unresponsiveto steroid treatment, have frequent relapses, or cannot be tapered off steroids after a few months.Platelets which have been bound by antibodies are taken up by macrophages in the spleen(which have Fc receptors), and so removal of the spleen reduces platelet destruction. Theprocedure is potentially risky in ITP cases due to the increased possibility of significant bleedingduring surgery. Durable remission following splenectomy is achieved in 60 - 80 percent of ITPcases.[34] Even though there is a consensus regarding the short-term efficacy of splenectomy,findings on its long-term efficacy and side-effects are controversial.[33][35] After splenectomy,11.6 - 75 percent of ITP cases relapsed, and 8.7 - 40 percent of ITP cases had no response tosplenectomy.[33][36][37][38] The use of splenectomy to treat ITP has diminished since thedevelopment of steroid therapy and other pharmaceutical remedies.[39]Platelet transfusion alone is normally not recommended except in an emergency and is usuallyunsuccessful in producing a long-term platelet count increase. This is because the underlyingautoimmune mechanism that is destroying the patient's platelets will also destroy donorplatelets, and so platelet transfusions are not considered a long-term treatment option.In adults, particularly those living in areas with a high prevalence of Helicobacter pylori (whichnormally inhabits the stomach wall and has been associated with peptic ulcers), identificationand treatment of this infection has been shown to improve platelet counts in a third of patients.In a fifth, the platelet count normalized completely; this response rate is similar to that found intreatment with rituximab, which is more expensive and less safe.[40] In children, this approach isSurgeryPlatelet transfusionH. pylori eradication
not supported by evidence, except in high prevalence areas. Urea breath testing and stool antigentesting perform better than serology-based tests; moreover, serology may be false-positive aftertreatment with IVIG.[41]Dapsone (also called diphenylsulfone, DDS, or avlosulfon) is an anti-infective sulfonemedication. Dapsone may also be helpful in treating lupus, rheumatoid arthritis, and as asecond-line treatment for ITP. The mechanism by which dapsone assists in ITP is unclear butan increased platelet count is seen in 40–60 percent of recipients.[42][43]The off-label use of rituximab, a chimeric monoclonal antibody against the B cell surfaceantigen CD20, may sometimes be an effective alternative to splenectomy. However,significant side-effects can occur, and randomized controlled trials are inconclusive.[44]It is uncommon for people with ITP to present with severe bleeding (only 5% of affected people).However, within five years of diagnosis, 15% of affected individuals are hospitalized withbleeding complications.A normal platelet count is considered to be in the range of 150,000–450,000 per microlitre (μl)of blood for most healthy individuals. Hence one may be considered thrombocytopenic belowthat range, although the threshold for a diagnosis of ITP is not tied to any specific number.The incidence of ITP is estimated at 50–100 new cases per million per year, with childrenaccounting for half of that number. At least 70 percent of childhood cases will end up inremission within six months, even without treatment.[45][46][47] Moreover, a third of theremaining chronic cases will usually remit during follow-up observation, and another third willend up with only mild thrombocytopenia (defined as a platelet count above 50,000).[45] Anumber of immune related genes and polymorphisms have been identified as influencingpredisposition to ITP, with FCGR3a-V158 allele and KIRDS2/DL2 increasing susceptibility andKIR2DS5 shown to be protective.[48][49]ITP is usually chronic in adults[50] and the probability of durable remission is 20–40percent.[18] The male to female ratio in the adult group varies from 1:1.2 to 1.7 in most ageranges (childhood cases are roughly equal for both sexes) and the median age of adults at thediagnosis is 56–60.[12] The ratio between male and female adult cases tends to widen with age. In the United States, the adult chronic population is thought to be approximately 60,000—withwomen outnumbering men approximately 2 to 1, which has resulted in ITP being designated anorphan disease.[51]The mortality rate due to chronic ITP varies but tends to be higher relative to the generalpopulation for any age range. In a study conducted in Great Britain, it was noted that ITP causesan approximately 60 percent higher rate of mortality compared to sex- and age-matched subjectswithout ITP. This increased risk of death with ITP is largely concentrated in the middle-agedand elderly. Ninety-six percent of reported ITP-related deaths were individuals 45 years orolder. No significant difference was noted in the rate of survival between males and females.[52]Other agentsPrognosisEpidemiologyPregnancy
Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own plateletsand will also cross the placenta and react against fetal platelets. Therefore, ITP is a significantcause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affectedby ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebralhemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).[53][54]No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatalthrombocytopenia is increased with:[55]Mothers with a history of splenectomy for ITPMothers who had a previous infant affected with ITPGestational (maternal) platelet count less than 100,000/uLIt is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITPshould be tested for serum antiplatelet antibodies. A woman with symptomaticthrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for theirITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count isnot generally performed as ITP-induced thrombocytopenia in the fetus is generally less severethan NAIT. Platelet transfusions may be performed in newborns, depending on the degree ofthrombocytopenia. It is recommended that neonates be followed with serial platelet counts forthe first few days after birth.[53][55]After initial reports by the Portuguese physician Amato Lusitano in 1556 and Lazarus de laRivière (physician to the King of France) in 1658, it was the German physician and poet PaulGottlieb Werlhof who in 1735 wrote the most complete initial report of the purpura of ITP.Platelets were unknown at the time.[56] The name \"Werlhof's disease\" was used more widelybefore the current descriptive name became more popular.[56][57] Platelets were described in theearly 19th century, and in the 1880s several investigators linked the purpura with abnormalitiesin the platelet count.[56][58] The first report of a successful therapy for ITP was in 1916, when ayoung Polish medical student, Paul Kaznelson, described a female patient's response to asplenectomy.[56] Splenectomy remained a first-line remedy until the introduction of steroidtherapy in the 1950s.[56]1. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. (March 2009).\"Standardization of terminology, definitions and outcome criteria in immunethrombocytopenic purpura of adults and children: report from an international working group\"(https://doi.org/10.1182%2Fblood-2008-07-162503). Blood. 113 (11): 2386–93.doi 10.1182/blood-2008-07-162503 (https://doi.org/10.1182%2Fblood-2008-07-162503):.PMID 19005182 (https://pubmed.ncbi.nlm.nih.gov/19005182).2. Lambert MP, Gernsheimer TB (May 2017). \"Clinical updates in adult immunethrombocytopenia\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813736). Blood. 129(21): 2829–2835. doi 10.1182/blood-2017-03-754119 (https://doi.org/10.1182%2Fblood-2017:-03-754119) PMC 5813736 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813736). .PMID 28416506 (https://pubmed.ncbi.nlm.nih.gov/28416506).HistoryReferences
3. Cines DB, McMillan R (2005). \"Management of adult idiopathic thrombocytopenic purpura\".Annual Review of Medicine. 56: 425–42. doi 10.1146/annurev.med.56.082103.104644 (http:s://doi.org/10.1146%2Fannurev.med.56.082103.104644) PMID 15660520 (https://pubmed.n. cbi.nlm.nih.gov/15660520).4. \"Immune Thrombocytopenic Purpura\" (https://www.lecturio.com/concepts/immune-thrombocytopenic-purpura/). The Lecturio Medical Concept Library. Retrieved 27 July 2021.5. Coopamah MD, Garvey MB, Freedman J, Semple JW (January 2003). \"Cellular immunemechanisms in autoimmune thrombocytopenic purpura: An update\". Transfusion MedicineReviews. 17 (1): 69–80. doi 10.1053/tmrv.2003.50004 (https://doi.org/10.1053%2Ftmrv.2003.:50004) PMID 12522773 (https://pubmed.ncbi.nlm.nih.gov/12522773). .6. Schwartz RS (November 2007). \"Immune thrombocytopenic purpura--from agony to agonist\".The New England Journal of Medicine. 357 (22): 2299–301. doi 10.1056/NEJMe0707126 (htt:ps://doi.org/10.1056%2FNEJMe0707126) PMID 18046034 (https://pubmed.ncbi.nlm.nih.gov/. 18046034) S2CID 9765360 (https://api.semanticscholar.org/CorpusID:9765360). .7. \"Immune Thrombocytopenic Purpura\" (https://www.lecturio.com/concepts/immune-thrombocytopenic-purpura/). The Lecturio Medical Concept Library. Retrieved 27 July 2021.8. Semple JW, Freedman J (November 1991). \"Increased antiplatelet T helper lymphocytereactivity in patients with autoimmune thrombocytopenia\" (https://doi.org/10.1182%2Fblood.V78.10.2619.2619). Blood. 78 (10): 2619–25. doi 10.1182/blood.V78.10.2619.2619 (https://do:i.org/10.1182%2Fblood.V78.10.2619.2619) PMID 1840468 (https://pubmed.ncbi.nlm.nih.go. v/1840468).9. Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, Amadori S(August 2008). \"Analysis of regulatory T-cell changes in patients with idiopathicthrombocytopenic purpura receiving B cell-depleting therapy with rituximab\" (https://doi.org/10.1182%2Fblood-2007-12-129262). Blood. 112 (4): 1147–50. doi 10.1182/blood-2007-12-:129262 (https://doi.org/10.1182%2Fblood-2007-12-129262) PMID 18375792 (https://pubme. d.ncbi.nlm.nih.gov/18375792).10. Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, Yazdanbakhsh K (August 2008). \"Defectivecirculating CD25 regulatory T cells in patients with chronic immune thrombocytopenicpurpura\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515134). Blood. 112 (4): 1325–8.doi 10.1182/blood-2008-01-135335 (https://doi.org/10.1182%2Fblood-2008-01-135335):.PMC 2515134 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515134) PMID 18420827 (ht. tps://pubmed.ncbi.nlm.nih.gov/18420827).11. Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, et al. (August 2008).\"Rituximab efficacy and safety in adult splenectomy candidates with chronic immunethrombocytopenic purpura: results of a prospective multicenter phase 2 study\" (https://doi.org/10.1182%2Fblood-2008-01-131029). Blood. 112 (4): 999–1004. doi 10.1182/blood-2008-:01-131029 (https://doi.org/10.1182%2Fblood-2008-01-131029) PMID 18463354 (https://pub. med.ncbi.nlm.nih.gov/18463354).12. Cines DB, Bussel JB (October 2005). \"How I treat idiopathic thrombocytopenic purpura(ITP)\" (https://doi.org/10.1182%2Fblood-2004-12-4598). Blood. 106 (7): 2244–51.doi 10.1182/blood-2004-12-4598 (https://doi.org/10.1182%2Fblood-2004-12-4598):.PMID 15941913 (https://pubmed.ncbi.nlm.nih.gov/15941913).13. Hansen DL, Möller S, Andersen K, Gaist D, Frederiksen H (October 2019). \"Evans syndromein adults - incidence, prevalence, and survival in a nationwide cohort\" (https://portal.findresearcher.sdu.dk/da/publications/4a70d3db-5a31-4848-9d1a-2b6d1286feb2). American Journalof Hematology. 94 (10): 1081–1090. doi 10.1002/ajh.25574 (https://doi.org/10.1002%2Fajh.2:5574) PMID 31292991 (https://pubmed.ncbi.nlm.nih.gov/31292991) S2CID 195879785 (http. . s://api.semanticscholar.org/CorpusID:195879785).14. Michel M, Chanet V, Dechartres A, Morin AS, Piette JC, Cirasino L, et al. (October 2009).\"The spectrum of Evans syndrome in adults: new insight into the disease based on theanalysis of 68 cases\" (https://doi.org/10.1182%2Fblood-2009-04-215368). Blood. 114 (15):3167–72. doi 10.1182/blood-2009-04-215368 (https://doi.org/10.1182%2Fblood-2009-04-215:368) PMID 19638626 (https://pubmed.ncbi.nlm.nih.gov/19638626). .
15. \"Diagnosis and treatment of idiopathic thrombocytopenic purpura: recommendations of theAmerican Society of Hematology. The American Society of Hematology ITP PracticeGuideline Panel\". Annals of Internal Medicine. 126 (4): 319–26. February 1997.doi 10.7326/0003-4819-126-4-199702150-00010 (https://doi.org/10.7326%2F0003-4819-126:-4-199702150-00010) PMID 9036806 (https://pubmed.ncbi.nlm.nih.gov/9036806). .S2CID 53089071 (https://api.semanticscholar.org/CorpusID:53089071).16. Liesner RJ, Machin SJ (March 1997). \"ABC of clinical haematology. Platelet disorders\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126215). BMJ. 314 (7083): 809–12.doi 10.1136/bmj.314.7083.809 (https://doi.org/10.1136%2Fbmj.314.7083.809):.PMC 2126215 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126215) PMID 9081003 (htt. ps://pubmed.ncbi.nlm.nih.gov/9081003).17. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA (April 2011). \"TheAmerican Society of Hematology 2011 evidence-based practice guideline for immunethrombocytopenia\" (https://doi.org/10.1182%2Fblood-2010-08-302984). Blood. 117 (16):4190–207. doi 10.1182/blood-2010-08-302984 (https://doi.org/10.1182%2Fblood-2010-08-30:2984) PMID 21325604 (https://pubmed.ncbi.nlm.nih.gov/21325604). .18. Stevens W, Koene H, Zwaginga JJ, Vreugdenhil G (November 2006). \"Chronic idiopathicthrombocytopenic purpura: present strategy, guidelines and new insights\". The NetherlandsJournal of Medicine. 64 (10): 356–63. PMID 17122451 (https://pubmed.ncbi.nlm.nih.gov/17122451).19. Buchman AL (October 2001). \"Side effects of corticosteroid therapy\". Journal of ClinicalGastroenterology. 33 (4): 289–94. doi 10.1097/00004836-200110000-00006 (https://doi.org/1:0.1097%2F00004836-200110000-00006) PMID 11588541 (https://pubmed.ncbi.nlm.nih.gov/. 11588541) S2CID 23828538 (https://api.semanticscholar.org/CorpusID:23828538). .20. Psaila B, Bussel JB (October 2008). \"Refractory immune thrombocytopenic purpura: currentstrategies for investigation and management\" (https://doi.org/10.1111%2Fj.1365-2141.2008.07275.x). British Journal of Haematology. 143 (1): 16–26. doi 10.1111/j.1365-:2141.2008.07275.x (https://doi.org/10.1111%2Fj.1365-2141.2008.07275.x) PMID 18573111. (https://pubmed.ncbi.nlm.nih.gov/18573111) S2CID 38433249 (https://api.semanticscholar.or. g/CorpusID:38433249).21. van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R (March 2004). \"TheCatharanthus alkaloids: pharmacognosy and biotechnology\". Current Medicinal Chemistry.11 (5): 607–28. doi 10.2174/0929867043455846 (https://doi.org/10.2174%2F092986704345:5846) PMID 15032608 (https://pubmed.ncbi.nlm.nih.gov/15032608). .22. Raviña E (2011). \"Vinca alkaloids\" (https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157). The evolution of drug discovery: From traditional medicines to modern drugs. JohnWiley & Sons. pp. 157–159. ISBN 9783527326693.23. Cooper R, Deakin JJ (2016). \"Africa's gift to the world\" (https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46). Botanical Miracles: Chemistry of Plants That Changed theWorld. CRC Press. pp. 46–51. ISBN 9781498704304.24. Kuboyama T, Yokoshima S, Tokuyama H, Fukuyama T (August 2004). \"Stereocontrolled totalsynthesis of (+)-vincristine\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514417).Proceedings of the National Academy of Sciences of the United States of America. 101 (33):11966–70. doi 10.1073/pnas.0401323101 (https://doi.org/10.1073%2Fpnas.0401323101):.PMC 514417 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514417) PMID 15141084 (http. s://pubmed.ncbi.nlm.nih.gov/15141084).25. Keglevich P, Hazai L, Kalaus G, Szántay C (May 2012). \"Modifications on the basic skeletonsof vinblastine and vincristine\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268133).Molecules. 17 (5): 5893–914. doi 10.3390/molecules17055893 (https://doi.org/10.3390%2Fm:olecules17055893) PMC 6268133. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268133) PMID 22609781 (https://pubmed.n. cbi.nlm.nih.gov/22609781).26. Ishida Y, Tomiyama Y, eds. (2017). Autoimmune Thrombocytopenia (https://books.google.com/books?id=xcgmDwAAQBAJ) Springer Nature ISBN 9789811041426. . .
27. \"Idiopathic thrombocytopenic purpura: Treatments and Drugs\" (http://www.mayoclinic.com/health/idiopathic-thrombocytopenic-purpura/DS00844/DSECTION=treatments%2Dand%2Ddrugs). Mayo Clinic. Retrieved October 16, 2012.28. Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. (October 2006).\"AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP\". The New England Journalof Medicine. 355 (16): 1672–81. doi 10.1056/NEJMoa054626 (https://doi.org/10.1056%2FNE:JMoa054626) PMID 17050891 (https://pubmed.ncbi.nlm.nih.gov/17050891). .29. Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, et al. (November 2010).\"Romiplostim or standard of care in patients with immune thrombocytopenia\". The NewEngland Journal of Medicine. 363 (20): 1889–99. doi 10.1056/NEJMoa1002625 (https://doi.o:rg/10.1056%2FNEJMoa1002625) PMID 21067381 (https://pubmed.ncbi.nlm.nih.gov/210673. 81) S2CID 22991485 (https://api.semanticscholar.org/CorpusID:22991485). .30. http://www.amgen.com/media/pr.jsp?year=200831. Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. (November 2007).\"Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura\". The NewEngland Journal of Medicine. 357 (22): 2237–47. doi 10.1056/NEJMoa073275 (https://doi.or:g/10.1056%2FNEJMoa073275) PMID 18046028 (https://pubmed.ncbi.nlm.nih.gov/1804602. 8).32. \"FDA approves Promacta (eltrombopag), the first oral medication to increase plateletproduction for people with serious blood disorder\" (https://web.archive.org/web/20101227031913/http://www.gsk.com/media/pressreleases/2008/2008_pressrelease_10127.htm) (Pressrelease). GlaxoSmithKline. 2008-11-20. Archived from the original (http://www.gsk.com/media/pressreleases/2008/2008_pressrelease_10127.htm) on 2010-12-27. Retrieved 2008-11-25.33. Kara-Jovanović A, Suvajdžić-Vuković N (2020-04-30). \"Clinical Presentation and Therapy ofPrimary Immune Thrombocytopenia Resistant to Splenectomy\" (http://ijms.info/IJMS/article/view/436). International Journal of Medical Students. (1): 11–14. 8doi 10.5195/ijms.2020.436:(https://doi.org/10.5195%2Fijms.2020.436) ISSN 2076-6327 (https://www.worldcat.org/issn/2. 076-6327).34. Chaturvedi S, Arnold DM, McCrae KR (March 2018). \"Splenectomy for immunethrombocytopenia: down but not out\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855018). Blood. 131 (11): 1172–1182. doi 10.1182/blood-2017-09-742353 (https://doi.org/10.1182%:2Fblood-2017-09-742353) PMC 5855018 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC58. 55018) PMID 29295846 (https://pubmed.ncbi.nlm.nih.gov/29295846). .35. Vianelli N, Galli M, de Vivo A, Intermesoli T, Giannini B, Mazzucconi MG, et al. (January2005). \"Efficacy and safety of splenectomy in immune thrombocytopenic purpura: long-termresults of 402 cases\". Haematologica. 90 (1): 72–7. PMID 15642672 (https://pubmed.ncbi.nlm.nih.gov/15642672).36. McMillan R, Durette C (August 2004). \"Long-term outcomes in adults with chronic ITP aftersplenectomy failure\". Blood. 104 (4): 956–60. doi 10.1182/blood-2003-11-3908 (https://doi.or:g/10.1182%2Fblood-2003-11-3908) PMID 15100149 (https://pubmed.ncbi.nlm.nih.gov/1510. 0149).37. Vianelli N, Palandri F, Polverelli N, Stasi R, Joelsson J, Johansson E, et al. (June 2013).\"Splenectomy as a curative treatment for immune thrombocytopenia: a retrospective analysisof 233 patients with a minimum follow up of 10 years\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669442). Haematologica. 98 (6): 875–80. doi 10.3324/haematol.2012.075648 (http:s://doi.org/10.3324%2Fhaematol.2012.075648) PMC 3669442 (https://www.ncbi.nlm.nih.go. v/pmc/articles/PMC3669442) PMID 23144195 (https://pubmed.ncbi.nlm.nih.gov/23144195). .38. Ahmed R, Devasia AJ, Viswabandya A, Lakshmi KM, Abraham A, Karl S, et al. (September2016). \"Long-term outcome following splenectomy for chronic and persistent immunethrombocytopenia (ITP) in adults and children : Splenectomy in ITP\". Annals of Hematology.95 (9): 1429–34. doi 10.1007/s00277-016-2738-3 (https://doi.org/10.1007%2Fs00277-016-27:38-3) PMID 27370992 (https://pubmed.ncbi.nlm.nih.gov/27370992) S2CID 23025470 (http. . s://api.semanticscholar.org/CorpusID:23025470).
39. Bhatt NS, Bhatt P, Donda K, Dapaah-Siakwan F, Chaudhari R, Linga VG, et al. (July 2018).\"Temporal trends of splenectomy in pediatric hospitalizations with immunethrombocytopenia\". Pediatric Blood & Cancer. 65 (7): e27072. doi 10.1002/pbc.27072 (http:s://doi.org/10.1002%2Fpbc.27072) PMID 29637697 (https://pubmed.ncbi.nlm.nih.gov/29637. 697) S2CID 4778713 (https://api.semanticscholar.org/CorpusID:4778713). .40. Stasi R, Sarpatwari A, Segal JB, Osborn J, Evangelista ML, Cooper N, et al. (February2009). \"Effects of eradication of Helicobacter pylori infection in patients with immunethrombocytopenic purpura: a systematic review\" (https://doi.org/10.1182%2Fblood-2008-07-167155). Blood. 113 (6): 1231–40. doi 10.1182/blood-2008-07-167155 (https://doi.org/10.118:2%2Fblood-2008-07-167155) PMID 18945961 (https://pubmed.ncbi.nlm.nih.gov/18945961). .41. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. (January2010). \"International consensus report on the investigation and management of primaryimmune thrombocytopenia\" (https://doi.org/10.1182%2Fblood-2009-06-225565). Blood. 115(2): 168–86. doi 10.1182/blood-2009-06-225565 (https://doi.org/10.1182%2Fblood-2009-06-2:25565) PMID 19846889 (https://pubmed.ncbi.nlm.nih.gov/19846889). .42. Godeau B, Durand JM, Roudot-Thoraval F, Tennezé A, Oksenhendler E, Kaplanski G, et al.(May 1997). \"Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66cases\" (https://doi.org/10.1046%2Fj.1365-2141.1997.412687.x). British Journal ofHaematology. 97 (2): 336–9. doi 10.1046/j.1365-2141.1997.412687.x (https://doi.org/10.104:6%2Fj.1365-2141.1997.412687.x) PMID 9163598 (https://pubmed.ncbi.nlm.nih.gov/916359. 8) S2CID 23283382 (https://api.semanticscholar.org/CorpusID:23283382). .43. Wozel G, Blasum C (March 2014). \"Dapsone in dermatology and beyond\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927068). Archives of Dermatological Research. 306 (2): 103–24. doi 10.1007/s00403-013-1409-7 (https://doi.org/10.1007%2Fs00403-013-1409-7):.PMC 3927068 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927068) PMID 24310318 (ht. tps://pubmed.ncbi.nlm.nih.gov/24310318).44. National Institute for Health and Care Excellence. Immune (idiopathic) thrombocytopenicpurpura: rituximab. October 2014. [1] (https://www.nice.org.uk/advice/esuom35)45. Watts RG (October 2004). \"Idiopathic thrombocytopenic purpura: a 10-year natural historystudy at the childrens hospital of alabama\". Clinical Pediatrics. 43 (8): 691–702.doi 10.1177/000992280404300802 (https://doi.org/10.1177%2F000992280404300802):.PMID 15494875 (https://pubmed.ncbi.nlm.nih.gov/15494875) S2CID 43752571 (https://api.s. emanticscholar.org/CorpusID:43752571).46. Treutiger I, Rajantie J, Zeller B, Henter JI, Elinder G, Rosthøj S (August 2007). \"Doestreatment of newly diagnosed idiopathic thrombocytopenic purpura reduce morbidity?\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2083887). Archives of Disease in Childhood. 92(8): 704–7. doi 10.1136/adc.2006.098442 (https://doi.org/10.1136%2Fadc.2006.098442):.PMC 2083887 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2083887) PMID 17460024 (ht. tps://pubmed.ncbi.nlm.nih.gov/17460024).47. Ou CY, Hsieh KS, Chiou YH, Chang YH, Ger LP (2006). \"A comparative study of initial use ofintravenous immunoglobulin and prednisolone treatments in childhood idiopathicthrombocytopenic purpur\". Acta Paediatrica Taiwanica = Taiwan Er Ke Yi Xue Hui Za Zhi. 47(5): 226–31. PMID 17352309 (https://pubmed.ncbi.nlm.nih.gov/17352309).48. Nourse JP, Lea R, Crooks P, Wright G, Tran H, Catalano J, et al. (January 2012). \"TheKIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immunethrombocytopenia independently of FCGR3a-158 polymorphisms\". Blood Coagulation &Fibrinolysis. 23 (1): 45–50. doi 10.1097/mbc.0b013e32834d7ce3 (https://doi.org/10.1097%2F:mbc.0b013e32834d7ce3) PMID 22024796 (https://pubmed.ncbi.nlm.nih.gov/22024796). .S2CID 3327902 (https://api.semanticscholar.org/CorpusID:3327902).49. Seymour LA, Nourse JP, Crooks P, Wockner L, Bird R, Tran H, Gandhi MK (March 2014).\"The presence of KIR2DS5 confers protection against adult immune thrombocytopenia\".Tissue Antigens. 83 (3): 154–60. doi 10.1111/tan.12295 (https://doi.org/10.1111%2Ftan.1229:5) PMID 24571473 (https://pubmed.ncbi.nlm.nih.gov/24571473). .
Classification ICD-10: D69.3 (https://icd.who.int/browse10/2019/en#/D69.3) · ICD-9-CM:287.31 (http://www.icd9data.com/getICD9Code.ashx?icd9=287.31) · OMIM:188030 (https://omim.org/entry/188030) · MeSH:D016553 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D016553) ·DiseasesDB: 6673(http://www.disease50. Cines DB, Blanchette VS (March 2002). \"Immune thrombocytopenic purpura\". The NewEngland Journal of Medicine. 346 (13): 995–1008. doi 10.1056/NEJMra010501 (https://doi.or:g/10.1056%2FNEJMra010501) PMID 11919310. (https://pubmed.ncbi.nlm.nih.gov/11919310).51. \"Amgen to Discuss Romiplostim BLA\"(https://www.drugs.com/nda/romiplostim_080312.html). drugs.com. March 12, 2008.Retrieved 2008-11-04.52. Schoonen WM, Kucera G, Coalson J, Li L, Rutstein M, Mowat F, et al. (April 2009).\"Epidemiology of immune thrombocytopenic purpura in the General Practice ResearchDatabase\" (https://doi.org/10.1111%2Fj.1365-2141.2009.07615.x). British Journal ofHaematology. 145 (2): 235–44. doi 10.1111/j.1365-2141.2009.07615.x (https://doi.org/10.111:1%2Fj.1365-2141.2009.07615.x) PMID 19245432 (https://pubmed.ncbi.nlm.nih.gov/192454. 32) S2CID 45178771 (https://api.semanticscholar.org/CorpusID:45178771). .53. Roback et al. AABB Technical Manual, 16th Ed. Bethesda, AABB Press, 2008.54. Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG (December 2003). \"A retrospective11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura\" (https://doi.org/10.1182%2Fblood-2002-10-3317). Blood. 102 (13): 4306–11. doi 10.1182/blood-2002-10-:3317 (https://doi.org/10.1182%2Fblood-2002-10-3317) PMID 12947011 (https://pubmed.ncb. i.nlm.nih.gov/12947011).55. Mais DD. ASCP Quick Compendium of Clinical Pathology. Chicago: ASCP Press, 2009.56. Stasi R, Newland AC (May 2011). \"ITP: a historical perspective\". British Journal ofHaematology. 153 (4): 437–50. doi 10.1111/j.1365-2141.2010.08562.x (https://doi.org/10.111:1%2Fj.1365-2141.2010.08562.x) PMID 21466538 (https://pubmed.ncbi.nlm.nih.gov/214665. 38) S2CID 37150678 (https://api.semanticscholar.org/CorpusID:37150678). .57. synd/3349 (http://www.whonamedit.com/synd.cfm/3349.html) at Who Named It?58. Liebman HA (2008). \"Immune thrombocytopenia (ITP): an historical perspective\" (https://doi.org/10.1182%2Fasheducation-2008.1.205). Hematology. American Society of Hematology.Education Program. 2008 (1): 205. doi 10.1182/asheducation-2008.1.205 (https://doi.org/10.1:182%2Fasheducation-2008.1.205) PMID 19074083 (https://pubmed.ncbi.nlm.nih.gov/19074. 083).External linksD
sdatabase.com/ddb6673.htm) ·SNOMED CT:234490009 (http://snomed.info/id/234490009)ExternalresourcesMedlinePlus:000535 (https://www.nlm.nih.gov/medlineplus/ency/article/000535.htm) ·eMedicine:emerg/282 (https://emedicine.medscape.com/emerg/282-overview) · PatientUK: Immunethrombocytopenicpurpura (https://patient.info/doctor/idiopathic-thrombocytopenic-purpura) ·Orphanet: 3002 (https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3002)Retrieved from \"https://en.wikipedia.org/w/index.php?title=Immune_thrombocytopenic_purpura&oldid=1042081350\"This page was last edited on 3 September 2021, at 03:40 (UTC).Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By usingthis site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the WikimediaFoundation, Inc., a non-profit organization.
StrokeOther namesCerebrovascular accident(CVA), cerebrovascular insult(CVI), brain attackCT scan of the brain showing a prior right-sidedischemic stroke from blockage of an artery.Changes on a CT may not be visible early on.[1]SpecialtyNeurology, stroke medicineSymptomsInability to move or feel on oneside of the body, problemsunderstanding or speaking,dizziness, loss of vision to oneside[2][3]ComplicationsPersistent vegetative state[4]CausesIschemic (blockage) andhemorrhagic (bleeding)[5]Risk factorsHigh blood pressure, tobaccosmoking, obesity, high bloodcholesterol, diabetes mellitus,previous TIA, end-stagekidney disease, atrialfibrillation[2][6][7]StrokeA stroke is a medical condition in which poorblood flow to the brain causes cell death.[5] Thereare two main types of stroke: ischemic, due to lackof blood flow, and hemorrhagic, due to bleeding.[5]Both cause parts of the brain to stop functioningproperly.[5] Signs and symptoms of a stroke mayinclude an inability to move or feel on one side ofthe body, problems understanding or speaking,dizziness, or loss of vision to one side.[2][3] Signsand symptoms often appear soon after the strokehas occurred.[3] If symptoms last less than one ortwo hours, the stroke is a transient ischemic attack(TIA), also called a mini-stroke.[3] A hemorrhagicstroke may also be associated with a severeheadache.[3] The symptoms of a stroke can bepermanent.[5] Long-term complications mayinclude pneumonia and loss of bladder control.[3]The main risk factor for stroke is high bloodpressure.[6] Other risk factors include tobaccosmoking, obesity, high blood cholesterol, diabetesmellitus, a previous TIA, end-stage kidney disease,and atrial fibrillation.[2][6][7] An ischemic stroke istypically caused by blockage of a blood vessel,though there are also less commoncauses.[12][13][14] A hemorrhagic stroke is causedby either bleeding directly into the brain or intothe space between the brain's membranes.[12][15]Bleeding may occur due to a ruptured brainaneurysm.[12] Diagnosis is typically based on aphysical exam and supported by medical imagingsuch as a CT scan or MRI scan.[8] A CT scan canrule out bleeding, but may not necessarily rule outischemia, which early on typically does not showup on a CT scan.[9] Other tests such as anelectrocardiogram (ECG) and blood tests are doneto determine risk factors and rule out otherpossible causes.[8] Low blood sugar may causesimilar symptoms.[8]Prevention includes decreasing risk factors,surgery to open up the arteries to the brain inthose with problematic carotid narrowing, andwarfarin in people with atrial fibrillation.[2]Aspirin or statins may be recommended byphysicians for prevention.[2] A stroke or TIA often
DiagnosticmethodBased on symptoms withmedical imaging typically usedto rule out bleeding[8][9]DifferentialdiagnosisLow blood sugar[8]TreatmentBased on the type[2]PrognosisAverage life expectancy 1year[2]Frequency42.4 million (2015)[10]Deaths6.3 million (2015)[11]requires emergency care.[5] An ischemic stroke, ifdetected within three to four and half hours, maybe treatable with a medication that can breakdown the clot.[2] Some hemorrhagic strokesbenefit from surgery.[2] Treatment to attemptrecovery of lost function is called strokerehabilitation, and ideally takes place in a strokeunit; however, these are not available in much ofthe world.[2]In 2013, approximately 6.9 million people had anischemic stroke and 3.4 million people had ahemorrhagic stroke.[16] In 2015, there were about42.4 million people who had previously had a stroke and were still alive.[10] Between 1990 and2010 the number of strokes which occurred each year decreased by approximately 10% in thedeveloped world and increased by 10% in the developing world.[17] In 2015, stroke was thesecond most frequent cause of death after coronary artery disease, accounting for 6.3 milliondeaths (11% of the total).[11] About 3.0 million deaths resulted from ischemic stroke while 3.3million deaths resulted from hemorrhagic stroke.[11] About half of people who have had a strokelive less than one year.[2] Overall, two thirds of strokes occurred in those over 65 years old.[17]ClassificationDefinitionIschemicHemorrhagicSigns and symptomsEarly recognitionSubtypesAssociated symptomsCausesThrombotic strokeEmbolic strokeCerebral hypoperfusionVenous thrombosisIntracerebral hemorrhageOtherSilent strokePathophysiologyIschemicHemorrhagicDiagnosisPhysical examinationImagingUnderlying causeMisdiagnosisContents
There are two main categories ofstrokes. Ischemic (top), typicallycaused by a blood clot in an artery(1a) resulting in brain death to theaffected area (2a). Hemorrhagic(bottom), caused by blood leakinginto or around the brain from aruptured blood vessel (1b) allowingblood to pool in the affected area(2b) thus increasing the pressure onthe brain.PreventionRisk factorsWomenPrevious stroke or TIAManagementIschemic strokeHemorrhagic strokeStroke unitRehabilitationOrthoticsSelf-managementPrognosisPhysical effectsEmotional and mental effectsEpidemiologyHistoryResearchSee alsoReferencesFurther readingExternal linksStrokes can be classified into two major categories: ischemicand hemorrhagic.[18] Ischemic strokes are caused byinterruption of the blood supply to the brain, whilehemorrhagic strokes result from the rupture of a bloodvessel or an abnormal vascular structure. About 87% ofstrokes are ischemic, the rest being hemorrhagic. Bleedingcan develop inside areas of ischemia, a condition known as\"hemorrhagic transformation.\" It is unknown how manyhemorrhagic strokes actually start as ischemic strokes.[2]In the 1970s the World Health Organization defined strokeas a \"neurological deficit of cerebrovascular cause thatpersists beyond 24 hours or is interrupted by death within24 hours\",[19] although the word \"stroke\" is centuries old.This definition was supposed to reflect the reversibility oftissue damage and was devised for the purpose, with thetime frame of 24 hours being chosen arbitrarily. The 24-hourlimit divides stroke from transient ischemic attack, which isa related syndrome of stroke symptoms that resolve completely within 24 hours.[2] With theavailability of treatments that can reduce stroke severity when given early, many now preferClassificationDefinition
A slice of brain from the autopsy ofa person who had an acute middlecerebral artery (MCA) strokealternative terminology, such as brain attack and acuteischemic cerebrovascular syndrome (modeled after heartattack and acute coronary syndrome, respectively), to reflectthe urgency of stroke symptoms and the need to actswiftly.[20]In an ischemic stroke, blood supply to part of the brain isdecreased, leading to dysfunction of the brain tissue in thatarea. There are four reasons why this might happen:1. Thrombosis (obstruction of a blood vessel by a blood clotforming locally)2. Embolism (obstruction due to an embolus from elsewhere in the body),[2]3. Systemic hypoperfusion (general decrease in blood supply, e.g., in shock)[21]4. Cerebral venous sinus thrombosis.[22]A stroke without an obvious explanation is termed cryptogenic (of unknown origin); thisconstitutes 30–40% of all ischemic strokes.[2][23]There are various classification systems for acute ischemic stroke. The Oxford Community StrokeProject classification (OCSP, also known as the Bamford or Oxford classification) relies primarilyon the initial symptoms; based on the extent of the symptoms, the stroke episode is classified astotal anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunarinfarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of thestroke, the area of the brain that is affected, the underlying cause, and the prognosis.[24][25] TheTOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinicalsymptoms as well as results of further investigations; on this basis, a stroke is classified as beingdue to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) an embolismoriginating in the heart, (3) complete blockage of a small blood vessel, (4) other determinedcause, (5) undetermined cause (two possible causes, no cause identified, or incompleteinvestigation).[26] Users of stimulants such as cocaine and methamphetamine are at a high riskfor ischemic strokes.[27]There are two main types of hemorrhagic stroke:[28][29]Intracerebral hemorrhage, which is basically bleeding within the brain itself (when an artery inthe brain bursts, flooding the surrounding tissue with blood), due to either intraparenchymalhemorrhage (bleeding within the brain tissue) or intraventricular hemorrhage (bleeding withinthe brain's ventricular system).Subarachnoid hemorrhage, which is basically bleeding that occurs outside of the brain tissuebut still within the skull, and precisely between the arachnoid mater and pia mater (thedelicate innermost layer of the three layers of the meninges that surround the brain).The above two main types of hemorrhagic stroke are also two different forms of intracranialhemorrhage, which is the accumulation of blood anywhere within the cranial vault; but the otherforms of intracranial hemorrhage, such as epidural hematoma (bleeding between the skull andthe dura mater, which is the thick outermost layer of the meninges that surround the brain) andIschemicHemorrhagic
CT scan of an intraparenchymalbleed (bottom arrow) withsurrounding edema (top arrow)A Centers for Disease Control andPrevention public serviceannouncement on emergencymedical treatment after or during astroke from 2021.subdural hematoma (bleeding in the subdural space), are notconsidered \"hemorrhagic strokes\".[30]Hemorrhagic strokes may occur on the background ofalterations to the blood vessels in the brain, such as cerebralamyloid angiopathy, cerebral arteriovenous malformationand an intracranial aneurysm, which can causeintraparenchymal or subarachnoid hemorrhage.In addition to neurological impairment, hemorrhagic strokesusually cause specific symptoms (for instance, subarachnoidhemorrhage classically causes a severe headache known as athunderclap headache) or reveal evidence of a previous headinjury.Stroke symptoms typically start suddenly, over seconds tominutes, and in most cases do not progress further. Thesymptoms depend on the area of the brain affected. The more extensive the area of the brainaffected, the more functions that are likely to be lost. Some forms of stroke can cause additionalsymptoms. For example, in intracranial hemorrhage, the affected area may compress otherstructures. Most forms of stroke are not associated with a headache, apart from subarachnoidhemorrhage and cerebral venous thrombosis and occasionally intracerebral hemorrhage.Various systems have been proposed to increase recognition of stroke. Different findings are ableto predict the presence or absence of stroke to different degrees. Sudden-onset face weakness,arm drift (i.e., if a person, when asked to raise both arms, involuntarily lets one arm driftdownward) and abnormal speech are the findings most likely to lead to the correct identificationof a case of stroke, increasing the likelihood by 5.5 when at least one of these is present.Similarly, when all three of these are absent, the likelihood of stroke is decreased (– likelihoodratio of 0.39).[31] While these findings are not perfect for diagnosing stroke, the fact that they canbe evaluated relatively rapidly and easily make them very valuable in the acute setting.A mnemonic to remember the warning signs of stroke isFAST (facial droop, arm weakness, speech difficulty, andtime to call emergency services),[32] as advocated by theDepartment of Health (United Kingdom) and the StrokeAssociation, the American Stroke Association, the NationalStroke Association (US), the Los Angeles Prehospital StrokeScreen (LAPSS)[33] and the Cincinnati Prehospital StrokeScale (CPSS).[34] Use of these scales is recommended byprofessional guidelines.[35] FAST is less reliable in therecognition of posterior circulation strokes.[36]For people referred to the emergency room, earlyrecognition of stroke is deemed important as this canexpedite diagnostic tests and treatments. A scoring systemcalled ROSIER (recognition of stroke in the emergency room) is recommended for this purpose;it is based on features from the medical history and physical examination.[35][37]Signs and symptomsEarly recognition
If the area of the brain affected includes one of the three prominent central nervous systempathways—the spinothalamic tract, corticospinal tract, and the dorsal column–medial lemniscuspathway, symptoms may include:hemiplegia and muscle weakness of the facenumbnessreduction in sensory or vibratory sensationinitial flaccidity (reduced muscle tone), replaced by spasticity (increased muscle tone),excessive reflexes, and obligatory synergies.[38]In most cases, the symptoms affect only one side of the body (unilateral). Depending on the partof the brain affected, the defect in the brain is usually on the opposite side of the body. However,since these pathways also travel in the spinal cord and any lesion there can also produce thesesymptoms, the presence of any one of these symptoms does not necessarily indicate a stroke. Inaddition to the above CNS pathways, the brainstem gives rise to most of the twelve cranialnerves. A brainstem stroke affecting the brainstem and brain, therefore, can produce symptomsrelating to deficits in these cranial nerves:altered smell, taste, hearing, or vision (total or partial)drooping of eyelid (ptosis) and weakness of ocular musclesdecreased reflexes: gag, swallow, pupil reactivity to lightdecreased sensation and muscle weakness of the facebalance problems and nystagmusaltered breathing and heart rateweakness in sternocleidomastoid muscle with inability to turn head to one sideweakness in tongue (inability to stick out the tongue or move it from side to side)If the cerebral cortex is involved, the CNS pathways can again be affected, but also can producethe following symptoms:aphasia (difficulty with verbal expression, auditory comprehension, reading and writing;Broca's or Wernicke's area typically involved)dysarthria (motor speech disorder resulting from neurological injury)apraxia (altered voluntary movements)visual field defectmemory deficits (involvement of temporal lobe)hemineglect (involvement of parietal lobe)disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe)lack of insight of his or her, usually stroke-related, disabilityIf the cerebellum is involved, ataxia might be present and this includes:altered walking gaitaltered movement coordinationvertigo and or disequilibriumSubtypesAssociated symptoms
Illustration of an embolic stroke,showing a blockage lodged in ablood vessel.Loss of consciousness, headache, and vomiting usually occur more often in hemorrhagic strokethan in thrombosis because of the increased intracranial pressure from the leaking bloodcompressing the brain.If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage oran embolic stroke.In thrombotic stroke, a thrombus[39] (blood clot) usuallyforms around atherosclerotic plaques. Since blockage of theartery is gradual, onset of symptomatic thrombotic strokes isslower than that of a hemorrhagic stroke. A thrombus itself(even if it does not completely block the blood vessel) canlead to an embolic stroke (see below) if the thrombus breaksoff and travels in the bloodstream, at which point it is calledan embolus. Two types of thrombosis can cause stroke:Large vessel disease involves the common and internalcarotid arteries, the vertebral artery, and the Circle ofWillis.[40] Diseases that may form thrombi in the largevessels include (in descending incidence):atherosclerosis, vasoconstriction (tightening of theartery), aortic, carotid or vertebral artery dissection,various inflammatory diseases of the blood vessel wall(Takayasu arteritis, giant cell arteritis, vasculitis),noninflammatory vasculopathy, Moyamoya disease andfibromuscular dysplasia.Small vessel disease involves the smaller arteries insidethe brain: branches of the circle of Willis, middle cerebralartery, stem, and arteries arising from the distal vertebraland basilar artery.[41] Diseases that may form thrombi in the small vessels include (indescending incidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as aresult of high blood pressure and aging) and fibrinoid degeneration (a stroke involving thesevessels is known as a lacunar stroke) and microatheroma (small atherosclerotic plaques).[42]Sickle-cell anemia, which can cause blood cells to clump up and block blood vessels, can also leadto stroke. A stroke is the second leading cause of death in people under 20 with sickle-cellanemia.[43] Air pollution may also increase stroke risk.[44]An embolic stroke refers to an arterial embolism (a blockage of an artery) by an embolus, atraveling particle or debris in the arterial bloodstream originating from elsewhere. An embolus ismost frequently a thrombus, but it can also be a number of other substances including fat (e.g.,from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually frominfectious endocarditis).[45]CausesThrombotic strokeEmbolic stroke
Because an embolus arises from elsewhere, local therapy solves the problem only temporarily.Thus, the source of the embolus must be identified. Because the embolic blockage is sudden inonset, symptoms usually are maximal at the start. Also, symptoms may be transient as theembolus is partially resorbed and moves to a different location or dissipates altogether.Emboli most commonly arise from the heart (especially in atrial fibrillation) but may originatefrom elsewhere in the arterial tree. In paradoxical embolism, a deep vein thrombosis embolizesthrough an atrial or ventricular septal defect in the heart into the brain.[45]Causes of stroke related to the heart can be distinguished between high and low-risk:[46]High risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of the mitral oraortic valve disease, artificial heart valves, known cardiac thrombus of the atrium or ventricle,sick sinus syndrome, sustained atrial flutter, recent myocardial infarction, chronic myocardialinfarction together with ejection fraction <28 percent, symptomatic congestive heart failurewith ejection fraction <30 percent, dilated cardiomyopathy, Libman-Sacks endocarditis,Marantic endocarditis, infective endocarditis, papillary fibroelastoma, left atrial myxoma andcoronary artery bypass graft (CABG) surgery.Low risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramen ovale(PFO), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale, leftventricular aneurysm without thrombus, isolated left atrial \"smoke\" on echocardiography (nomitral stenosis or atrial fibrillation), complex atheroma in the ascending aorta or proximalarch.Among those who have a complete blockage of one of the carotid arteries, the risk of stroke onthat side is about one percent per year.[47]A special form of embolic stroke is the embolic stroke of undetermined source (ESUS). Thissubset of cryptogenic stroke is defined as a non-lacunar brain infarct without proximal arterialstenosis or cardioembolic sources. About one out of six ischemic strokes could be classified asESUS.[48]Cerebral hypoperfusion is the reduction of blood flow to all parts of the brain. The reductioncould be to a particular part of the brain depending on the cause. It is most commonly due toheart failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result ofmyocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (lowblood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow isglobal, all parts of the brain may be affected, especially vulnerable \"watershed\" areas—borderzone regions supplied by the major cerebral arteries. A watershed stroke refers to the conditionwhen the blood supply to these areas is compromised. Blood flow to these areas does notnecessarily stop, but instead it may lessen to the point where brain damage can occur.Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, whichexceeds the pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagictransformation (leaking of blood into the damaged area) than other types of ischemic stroke.[22]Cerebral hypoperfusionVenous thrombosisIntracerebral hemorrhage
Histopathology at high magnification ofa normal neuron, and an ischemicstroke at approximately 24 hours onH&E stain: The neurons becomehypereosinophilic and there is aninfiltrate of neutrophils. There is slightedema and loss of normal architecturein the surrounding neuropil.It generally occurs in small arteries or arterioles and is commonly due to hypertension,[49]intracranial vascular malformations (including cavernous angiomas or arteriovenousmalformations), cerebral amyloid angiopathy, or infarcts into which secondary hemorrhage hasoccurred.[2] Other potential causes are trauma, bleeding disorders, amyloid angiopathy, illicitdrug use (e.g., amphetamines or cocaine). The hematoma enlarges until pressure fromsurrounding tissue limits its growth, or until it decompresses by emptying into the ventricularsystem, CSF or the pial surface. A third of intracerebral bleed is into the brain's ventricles. ICHhas a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoidhemorrhage (which technically may also be classified as a type of stroke[2]).Other causes may include spasm of an artery. This may occur due to cocaine.[50]A silent stroke is a stroke that does not have any outward symptoms, and people are typicallyunaware they have had a stroke. Despite not causing identifiable symptoms, a silent stroke stilldamages the brain and places the person at increased risk for both transient ischemic attack andmajor stroke in the future. Conversely, those who have had a major stroke are also at risk ofhaving silent strokes.[51] In a broad study in 1998, more than 11 million people were estimated tohave experienced a stroke in the United States. Approximately 770,000 of these strokes weresymptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokestypically cause lesions which are detected via the use of neuroimaging such as MRI. Silentstrokes are estimated to occur at five times the rate of symptomatic strokes.[52][53] The risk ofsilent stroke increases with age, but may also affect younger adults and children, especially thosewith acute anemia.[52][54]Ischemic stroke occurs because of a loss of blood supplyto part of the brain, initiating the ischemic cascade.[55]Brain tissue ceases to function if deprived of oxygen formore than 60 to 90 seconds, and after approximatelythree hours will suffer irreversible injury possibly leadingto the death of the tissue, i.e., infarction. (This is whyfibrinolytics such as alteplase are given only until threehours since the onset of the stroke.) Atherosclerosis maydisrupt the blood supply by narrowing the lumen of bloodvessels leading to a reduction of blood flow, by causingthe formation of blood clots within the vessel, or byreleasing showers of small emboli through thedisintegration of atherosclerotic plaques.[56] Embolicinfarction occurs when emboli formed elsewhere in thecirculatory system, typically in the heart as a consequenceof atrial fibrillation, or in the carotid arteries, break off,enter the cerebral circulation, then lodge in and block brain blood vessels. Since blood vessels inthe brain are now blocked, the brain becomes low in energy, and thus it resorts to usingOtherSilent strokePathophysiologyIschemic
anaerobic metabolism within the region of brain tissue affected by ischemia. Anaerobicmetabolism produces less adenosine triphosphate (ATP) but releases a by-product called lacticacid. Lactic acid is an irritant which could potentially destroy cells since it is an acid and disruptsthe normal acid-base balance in the brain. The ischemia area is referred to as the \"ischemicpenumbra\".[57]As oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energyphosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off aseries of interrelated events that result in cellular injury and death. A major cause of neuronalinjury is the release of the excitatory neurotransmitter glutamate. The concentration ofglutamate outside the cells of the nervous system is normally kept low by so-called uptakecarriers, which are powered by the concentration gradients of ions (mainly Na ) across the cell+membrane. However, stroke cuts off the supply of oxygen and glucose which powers the ionpumps maintaining these gradients. As a result, the transmembrane ion gradients run down, andglutamate transporters reverse their direction, releasing glutamate into the extracellular space.Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx ofcalcium which activates enzymes that digest the cells' proteins, lipids, and nuclear material.Calcium influx can also lead to the failure of mitochondria, which can lead further toward energydepletion and may trigger cell death due to programmed cell death.[58]Ischemia also induces production of oxygen free radicals and other reactive oxygen species.These react with and damage a number of cellular and extracellular elements. Damage to theblood vessel lining or endothelium is particularly important. In fact, many antioxidantneuroprotectants such as uric acid and NXY-059 work at the level of the endothelium and not inthe brain per se. Free radicals also directly initiate elements of the programmed cell deathcascade by means of redox signaling.[59]These processes are the same for any type of ischemic tissue and are referred to collectively asthe ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has littlerespiratory reserve and is completely dependent on aerobic metabolism, unlike most otherorgans.In addition to damaging effects on brain cells, ischemia and infarction can result in loss ofstructural integrity of brain tissue and blood vessels, partly through the release of matrixmetalloproteases, which are zinc- and calcium-dependent enzymes that break down collagen,hyaluronic acid, and other elements of connective tissue. Other proteases also contribute to thisprocess. The loss of vascular structural integrity results in a breakdown of the protective bloodbrain barrier that contributes to cerebral edema, which can cause secondary progression of thebrain injury.Hemorrhagic strokes are classified based on their underlying pathology. Some causes ofhemorrhagic stroke are hypertensive hemorrhage, ruptured aneurysm, ruptured AV fistula,transformation of prior ischemic infarction, and drug-induced bleeding.[60] They result in tissueinjury by causing compression of tissue from an expanding hematoma or hematomas. Inaddition, the pressure may lead to a loss of blood supply to affected tissue with resultinginfarction, and the blood released by brain hemorrhage appears to have direct toxic effects onbrain tissue and vasculature.[43][61] Inflammation contributes to the secondary brain injury afterhemorrhage.[61]Hemorrhagic
A CT showing early signs of amiddle cerebral artery stroke withloss of definition of the gyri and greywhite boundaryDens media sign in a patient withmiddle cerebral artery infarctionshown on the left. Right image after7 hours.Stroke is diagnosed through several techniques: aneurological examination (such as the NIHSS), CT scans(most often without contrast enhancements) or MRI scans,Doppler ultrasound, and arteriography. The diagnosis ofstroke itself is clinical, with assistance from the imagingtechniques. Imaging techniques also assist in determiningthe subtypes and cause of stroke. There is yet no commonlyused blood test for the stroke diagnosis itself, though bloodtests may be of help in finding out the likely cause ofstroke.[62] In deceased people, an autopsy of stroke may helpestablishing the time between stroke onset and death.A physical examination, including taking a medical history ofthe symptoms and a neurological status, helps giving anevaluation of the location and severity of a stroke. It can givea standard score on e.g., the NIH stroke scale.For diagnosing ischemic (blockage) stroke in the emergencysetting:[63]CT scans (without contrast enhancements)sensitivity= 16% (less than 10% within first 3 hours ofsymptom onset)specificity= 96%MRI scansensitivity= 83%specificity= 98%For diagnosing hemorrhagic stroke in the emergency setting:CT scans (without contrast enhancements)sensitivity= 89%specificity= 100%MRI scansensitivity= 81%specificity= 100%For detecting chronic hemorrhages, MRI scan is more sensitive.[64]DiagnosisPhysical examinationImaging
12-lead ECG of a patient with astroke, showing large deeplyinverted T-waves. Various ECGchanges may occur in people withstrokes and other brain disorders.For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may be helpful.SPECT documents cerebral blood flow and PET with FDG isotope the metabolic activity of theneurons.CT scans may not detect an ischemic stroke, especially if it is small, of recent onset, or in thebrainstem or cerebellum areas. A CT scan is more to rule out certain stroke mimics and detectbleeding.[9]When a stroke has been diagnosed, various other studiesmay be performed to determine the underlying cause. Withthe current treatment and diagnosis options available, it is ofparticular importance to determine whether there is aperipheral source of emboli. Test selection may vary sincethe cause of stroke varies with age, comorbidity and theclinical presentation. The following are commonly usedtechniques:an ultrasound/doppler study of the carotid arteries (todetect carotid stenosis) or dissection of the precerebralarteries;an electrocardiogram (ECG) and echocardiogram (toidentify arrhythmias and resultant clots in the heart whichmay spread to the brain vessels through the bloodstream);a Holter monitor study to identify intermittent abnormal heart rhythms;an angiogram of the cerebral vasculature (if a bleed is thought to have originated from ananeurysm or arteriovenous malformation);blood tests to determine if blood cholesterol is high, if there is an abnormal tendency tobleed, and if some rarer processes such as homocystinuria might be involved.For hemorrhagic strokes, a CT or MRI scan with intravascular contrast may be able to identifyabnormalities in the brain arteries (such as aneurysms) or other sources of bleeding, andstructural MRI if this shows no cause. If this too does not identify an underlying reason for thebleeding, invasive cerebral angiography could be performed but this requires access to thebloodstream with an intravascular catheter and can cause further strokes as well ascomplications at the insertion site and this investigation is therefore reserved for specificsituations.[65] If there are symptoms suggesting that the hemorrhage might have occurred as aresult of venous thrombosis, CT or MRI venography can be used to examine the cerebralveins.[65]Among people with ischemic strokes, misdiagnosis occurs 2 to 26% of the time.[66] A \"strokechameleon\" (SC) is stroke which is diagnosed as something else.[66][67]People not having a stroke may also be misdiagnosed as a stroke. Giving thrombolytics (clot-busting) in such cases causes intracerebral bleeding 1 to 2% of the time, which is less than that ofpeople with strokes. This unnecessary treatment adds to health care costs. Even so, theAHA/ASA guidelines state that starting intravenous tPA in possible mimics is preferred todelaying treatment for additional testing.[66]Underlying causeMisdiagnosis
Women, African-Americans, Hispanic-Americans, Asian and Pacific Islanders are more oftenmisdiagnosed for a condition other than stroke when in fact having a stroke. In addition, adultsunder 44 years of age are seven times more likely to have a stroke missed than are adults over 75years of age. This is especially the case for younger people with posterior circulation infarcts.[66]Some medical centers have used hyperacute MRI in experimental studies for persons initiallythought to have a low likelihood of stroke. And in some of these persons, strokes have beenfound which were then treated with thrombolytic medication.[66]Given the disease burden of strokes, prevention is an important public health concern.[68]Primary prevention is less effective than secondary prevention (as judged by the number neededto treat to prevent one stroke per year).[68] Recent guidelines detail the evidence for primaryprevention in stroke.[69] In those who are otherwise healthy, aspirin does not appear beneficialand thus is not recommended.[70] In people who have had a myocardial infarction or those witha high cardiovascular risk, it provides some protection against a first stroke.[71][72] In those whohave previously had a stroke, treatment with medications such as aspirin, clopidogrel, anddipyridamole may be beneficial.[71] The U.S. Preventive Services Task Force (USPSTF)recommends against screening for carotid artery stenosis in those without symptoms.[73]The most important modifiable risk factors for stroke are high blood pressure and atrialfibrillation although the size of the effect is small; 833 people have to be treated for 1 year toprevent one stroke.[74][75] Other modifiable risk factors include high blood cholesterol levels,diabetes mellitus, end-stage kidney disease,[7] cigarette smoking[76][77] (active and passive),heavy alcohol use,[78] drug use,[79] lack of physical activity, obesity, processed red meatconsumption,[80] and unhealthy diet.[81] Smoking just one cigarette per day increases the riskmore than 30%.[82] Alcohol use could predispose to ischemic stroke, as well as intracerebral andsubarachnoid hemorrhage via multiple mechanisms (for example, via hypertension, atrialfibrillation, rebound thrombocytosis and platelet aggregation and clotting disturbances).[83]Drugs, most commonly amphetamines and cocaine, can induce stroke through damage to theblood vessels in the brain and acute hypertension.[60][84] Migraine with aura doubles a person'srisk for ischemic stroke.[85][86] Untreated, celiac disease regardless of the presence of symptomscan be an underlying cause of stroke, both in children and adults.[87]High levels of physical activity reduce the risk of stroke by about 26%.[88] There is a lack of highquality studies looking at promotional efforts to improve lifestyle factors.[89] Nonetheless, giventhe large body of circumstantial evidence, best medical management for stroke includes adviceon diet, exercise, smoking and alcohol use.[90] Medication is the most common method of strokeprevention; carotid endarterectomy can be a useful surgical method of preventing stroke.High blood pressure accounts for 35–50% of stroke risk.[91] Blood pressure reduction of 10mmHg systolic or 5 mmHg diastolic reduces the risk of stroke by ~40%.[92] Lowering bloodpressure has been conclusively shown to prevent both ischemic and hemorrhagic strokes.[93][94]It is equally important in secondary prevention.[95] Even people older than 80 years and thosewith isolated systolic hypertension benefit from antihypertensive therapy.[96][97][98] Theavailable evidence does not show large differences in stroke prevention between antihypertensivePreventionRisk factorsBlood pressure
Search
Read the Text Version
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 16
- 17
- 18
- 19
- 20
- 21
- 22
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31
- 32
- 33
- 34
- 35
- 36
- 37
- 38
- 39
- 40
- 41
- 42
- 43
- 44
- 45
- 46
- 47
- 48
- 49
- 50
- 51
- 52
- 53
- 54
- 55
- 56
- 57
- 58
- 59
- 60
- 61
- 62
- 63
- 64
- 65
- 66
- 67
- 68
- 69
- 70
- 71
- 72
- 73
- 74
- 75
- 76
- 77
- 78
- 79
- 80
- 81
- 82
- 83
- 84
- 85
- 86
- 87
- 88
- 89
- 90
- 91
- 92
- 93
- 94
- 95
- 96
- 97
- 98
- 99
- 100
- 101
- 102
- 103
- 104
- 105
- 106
- 107
- 108
- 109
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 117
- 118
- 119
- 120
- 121
- 122
- 123
- 124
- 125
- 126
- 127
- 128
- 129
- 130
- 131
- 132
- 133
- 134
- 135
- 136
- 137
- 138
- 139
- 140
- 141
- 142
- 143
- 144
- 145
- 146
- 147
- 148
- 149
- 150
- 151
- 152
- 153
- 154
- 155
- 156
- 157
- 158
- 159
- 160
- 161
- 162
- 163
- 164
- 165
- 166
- 167
- 168
- 169
- 170
- 171
- 172
- 173
- 174
- 175
- 176
- 177
- 178
- 179
- 180
- 181
- 182
- 183
- 184
- 185
- 186
- 187
- 188
- 189
- 190
- 191
- 192
- 193
- 194
- 195
- 196
- 197
- 198
- 199
- 200
- 201
- 202
- 203
- 204
- 205
- 206
- 207
- 208
- 209
- 210
- 211
- 212
- 213
- 214
- 215
- 216
- 217
- 218
- 219
- 220
- 221
- 222
- 223
- 224
- 225
- 226
- 227
- 228
- 229
- 230
- 231
- 232
