Medical definitions and information for the V.A.E.R.S. reports Symptoms are Blood clotting disorders

MissKitt on https://misskitt.dreamhosters.comMedical definitions & information for the V.A.E.R.S. reports Where Symptom isCerebral venous sinus thrombosis¹ or Cerebral venousthrombosis¹ or Coagulopathy² or Deep vein thrombosis³ orDisseminated intravascular coagulation⁴or Embolism⁵ orIdiopathic thrombocytopenic purpura⁶ or Immunethrombocytopenia⁶ or Immune thrombocytopenic purpura⁶or Ischaemic stroke⁷ or Myocardial infarction ⁸or Petechiae⁹or Pulmonary embolism ¹⁰or Purpura¹¹ orThrombocytopenia¹² or Thrombosis ¹³or Vasculitis¹⁴Symptoms: Blood clotting disorders

MissKitt on https://misskitt.dreamhosters.comp. 3 synopsisp. 8 Cerebral venous sinus thrombosis¹p. 8 Cerebral venous thrombosis¹p. 19 Coagulopathy²p. 23 Deep vein thrombosis³p. 63 Disseminated intravascular coagulation⁴p. 71 Embolism⁵p. 75 Idiopathic thrombocytopenic purpura⁶p. 75 Immune thrombocytopenia⁶p. 75 Immune thrombocytopenic purpura⁶p. 88 stroke⁷p. 136 Myocardial infarction⁸p. 170 Petechiae⁹p. 174 Pulmonary embolism¹⁰p. 199 Purpura¹¹p. 202 Thrombocytopenia¹²p. 212 Thrombosis¹³p. 227 Vasculitis¹⁴

Where Symptom is Cerebral venous sinus thrombosis¹ or Cerebral venousthrombosis¹or Coagulopathy² or Deep vein thrombosis³ or Disseminatedintravascular coagulation⁴ or Embolism⁵ or Idiopathic thrombocytopenicpurpura⁶ or Immune thrombocytopenia⁶ or Immune thrombocytopenicpurpura⁶ orIschaemic stroke⁷ or Myocardial infarction⁸ or Petechiae⁹ or Pulmonaryembolism¹⁰ or Purpura¹¹ or Thrombocytopenia¹² or Thrombosis¹³ or Vasculitis¹⁴Cerebral venous sinus thrombosis¹ or Cerebral venous thrombosis¹Cerebral venous sinus thrombosis CVST cerebral venous and sinus thrombosis (), or cerebral venousthrombosis CVT (), is the presence of a blood clot in the dural venous sinuses (which drain blood from the brain),the cerebral veins, or both. Symptoms may include severe headache, visual symptoms, any of the symptomsof stroke such as weakness of the face and limbs on one side of the body, and seizures.The diagnosis is usually by computed tomography (CT scan) or magnetic resonance imaging (MRI) to demonstrateobstruction of the venous sinuses. After confirmation of the diagnosis, investigations may be performed to determine[2]the underlying cause, especially if one is not readily apparent.https://en.wikipedia.org/wiki/Cerebral_venous_sinus_thrombosisCoagulopathy²Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) isimpaired. This condition can cause a tendency toward prolonged or excessive bleeding ([1]bleeding diathesis), whichmay occur spontaneously or following an injury or medical and dental procedures.[citation needed]Of note, coagulopathies are sometimes erroneously referred to as \"clotting disorders\"; a clotting disorder is apredisposition to clot formation (thrombus), also known as a hypercoagulable state or thrombophilia.https://en.wikipedia.org/wiki/CoagulopathyDeep vein thrombosis³Deep vein thrombosis DVT () is the formation of a blood clot in a deep vein, most commonly in the legs orpelvis.[9][a] A minority of DVTs occur in the arms.[11] Symptoms can include pain, swelling, redness, and enlarged veinsin the affected area, but some DVTs have no symptoms. The most common life-threatening concern with DVT is the[1]potential for a clot to embolize (detach from the veins), travel as an embolus through the right side of the heart, andbecome lodged in a pulmonary artery that supplies blood to the lungs. This is called a pulmonary embolism (PE). DVTand PE comprise the cardiovascular disease of venous thromboembolism (VTE). About two-thirds of VTE manifests[2]as DVT only, with one-third manifesting as PE with or without DVT.[12] The most frequent long-termDVT complication is post-thrombotic syndrome, which can cause pain, swelling, a sensation of heaviness, itching, andin severe cases, ulcers. Recurrent VTE occurs in about 30% of those in the ten years following an initial VTE.[5][3]The mechanism behind DVT formation typically involves some combination of decreased blood flow,increased tendency to clot, changes to the blood vessel wall, and inflammation.[13] Risk factors include recent surgery,older age, active cancer obesity, , infection, inflammatory diseases, antiphospholipid syndrome, personal historyand family history of VTE, trauma, injuries, lack of movement, hormonal birth control pregnancy, , and the periodfollowing birth. VTE has a strong genetic component, accounting for approximately 50 to 60% of the variability in VTErates. Genetic factors include non-O [4]blood type, deficiencies of antithrombin protein C, , and protein S and themutations of factor V Leiden and prothrombin G20210A. In total, dozens of genetic risk factors have beenidentified.[4][14]https://en.wikipedia.org/wiki/Deep_vein_thrombosis

Disseminated intravascular coagulation⁴Disseminated intravascular coagulation DIC () is a condition in which blood clots form throughout the body,blocking small blood vessels. Symptoms may include [1]chest pain shortness of breath, , leg pain, problems speaking,or problems moving parts of the body. As [1]clotting factors and platelets are used up, bleeding may occur. This may[1]include blood in the urine blood in the stool, , or bleeding into the skin. Complications may include [1]organ failure.[2]Relatively common causes include sepsis surgery major trauma cancer, , , , and complications of pregnancy. Less [1]common causes include snake bites frostbite, , and burns. There are two main types: acute (rapid onset) and chronic[1](slow onset). Diagnosis is typically based on [1]blood tests. Findings may include [2]low platelets, low fibrinogen,high INR, or high D-dimer.[2]Treatment is mainly directed towards the underlying condition.[2][3] Other measures may includegiving platelets cryoprecipitate, , or fresh frozen plasma. Evidence to support these treatments, however, is[2]poor. [2]Heparin may be useful in the slowly developing form. About 1% of people admitted to hospital are affected by[2]the condition. In those with sepsis, rates are between 20% and 50%. The risk of death among those affected[4][4]varies from 20 to 50%.[4]https://en.wikipedia.org/wiki/Disseminated_intravascular_coagulationEmbolism⁵An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The [1]embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas gas (embolism amniotic fluid amniotic fluid embolism), (), or foreign material. An embolism can cause partial or totalblockage of blood flow in the affected vessel. Such a blockage (a [2]vascular occlusion) may affect a part of the bodydistant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called athromboembolism.An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionallyfor a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Suchtherapy is called embolization.https://en.wikipedia.org/wiki/EmbolismIdiopathic thrombocytopenic purpura⁶ or Immune thrombocytopenia⁶ or Immunethrombocytopenic purpura⁶Immune thrombocytopenic purpura ITP (), also known as idiopathic thrombocytopenic purpura or immunethrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with anormal bone marrow in the absence of other causes of low platelets. It causes a characteristic [1]red or purple bruise-like rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition inchildren and a chronic condition in adults. The acute form often follows an infection and spontaneously resolves withintwo months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.ITP is an autoimmune disease with antibodies detectable against several platelet surface structures.ITP is diagnosed by identifying a low platelet count on a complete blood count (a common blood test). However, sincethe diagnosis depends on the exclusion of other causes of a low platelet count, additional investigations (such asa bone marrow biopsy) may be necessary in some cases.In mild cases, only careful observation may be required but very low counts or significant bleeding may prompttreatment with corticosteroids intravenous immunoglobulin anti-D immunoglobulin, , , or immunosuppressivemedications. Refractory ITP (not responsive to conventional treatment or constant relapsing after splenectomy)requires treatment to reduce the risk of clinically significant bleeding. [2]Platelet transfusions may be used in severecases with very low platelet counts in people who are bleeding. Sometimes the body may compensate by makingabnormally large platelets.https://en.wikipedia.org/wiki/Immune_thrombocytopenic_purpura

Ischaemic stroke⁷A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of[5]stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop[5]functioning properly. Signs and symptoms of a stroke may include an [5]inability to move or feel on one side of thebody, problems understanding or speaking dizziness, , or loss of vision to one side.[2][3] Signs and symptoms oftenappear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a [3]transientischemic attack (TIA), also called a mini-stroke. A [3]hemorrhagic stroke may also be associated with a severeheadache. The symptoms of a stroke can be permanent. Long-term complications may[3][5]include pneumonia and loss of bladder control.[3]The main risk factor for stroke is high blood pressure. Other risk factors include [6]tobacco smoking obesity high blood, , cholesterol diabetes mellitus, , a previous TIA, end-stage kidney disease, and atrial fibrillation.[2][6][7] An ischemic strokeis typically caused by blockage of a blood vessel, though there are also less common causes.[12][13][14] A hemorrhagicstroke is caused by either bleeding directly into the brain or into the space between the brain'smembranes.[12][15] Bleeding may occur due to a ruptured brain aneurysm.[12] Diagnosis is typically based ona physical exam and supported by medical imaging such as a CT scan or MRI scan. A CT scan can rule out[8]bleeding, but may not necessarily rule out ischemia, which early on typically does not show up on a CT scan. Other[9]tests such as an electrocardiogram (ECG) and blood tests are done to determine risk factors and rule out otherpossible causes. [8]Low blood sugar may cause similar symptoms.[8]Prevention includes decreasing risk factors, surgery to open up the arteries to the brain in those withproblematic carotid narrowing, and warfarin in people with atrial fibrillation. [2]Aspirin or statins may be recommendedby physicians for prevention. A stroke or TIA often requires emergency care. An ischemic stroke, if detected within[2][5]three to four and half hours, may be treatable with a medication that can break down the clot. Some hemorrhagic [2]strokes benefit from surgery. Treatment to attempt recovery of lost function is called [2]stroke rehabilitation, and ideallytakes place in a stroke unit; however, these are not available in much of the world.[2]In 2013, approximately 6.9 million people had an ischemic stroke and 3.4 million people had a hemorrhagicstroke.[16] In 2015, there were about 42.4 million people who had previously had a stroke and were stillalive.[10] Between 1990 and 2010 the number of strokes which occurred each year decreased by approximately 10% inthe developed world and increased by 10% in the developing world.[17] In 2015, stroke was the second most frequentcause of death after coronary artery disease, accounting for 6.3 million deaths (11% of the total).[11] About 3.0 milliondeaths resulted from ischemic stroke while 3.3 million deaths resulted from hemorrhagic stroke.[11] About half of peoplewho have had a stroke live less than one year. Overall, two thirds of strokes occurred in those over 65 years old.[2][17]https://en.wikipedia.org/wiki/StrokeMyocardial infarction⁸A myocardial infarction MI (), commonly known as a heart attack, occurs when blood flow decreases or stops to apart of the heart, causing damage to the heart muscle. The most common symptom is [1]chest pain or discomfort whichmay travel into the shoulder, arm, back, neck or jaw. Often it occurs in the center or left side of the chest and lasts for[1]more than a few minutes. The discomfort may occasionally feel like [1]heartburn. Other symptoms may [1]include shortness of breath, nausea, feeling faint, a cold sweat or feeling tired. About 30% of people have atypical[1]symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel[8]tired.[11] Among those over 75 years old, about 5% have had an MI with little or no history of symptoms.[12] An MI maycause heart failure, an irregular heartbeat cardiogenic shock, or cardiac arrest.[3][4]Most MIs occur due to coronary artery disease. Risk factors include [3]high blood pressure smoking diabetes lack of, , , exercise obesity high blood cholesterol, , , poor diet and excessive alcohol intake.[5][6] The complete blockage ofa coronary artery caused by a rupture of an atherosclerotic plaque is usually the underlying mechanism of an MI. MIs[3]are less commonly caused by coronary artery spasms, which may be due to cocaine, significant emotional stress(commonly known as Takotsubo syndrome or broken heart syndrome) and extreme cold, among others.[13][14] Anumber of tests are useful to help with diagnosis, including electrocardiograms (ECGs), blood tests and coronaryangiography. An ECG, which is a recording of the heart's electrical activity, may confirm an [7]ST elevationMI (STEMI), if ST elevation is present.[8][15] Commonly used blood tests include troponin and less often creatinekinase MB.[7]https://en.wikipedia.org/wiki/Myocardial_infarction

Petechiae⁹A petechia (pl. petechiae) is a small (1–2 mm) red or purple spot on the skin or conjunctiva, caused by a minor bleedfrom broken capillary blood vessels. The word is derived from Latin 'petigo', meaning ‘scab' or 'eruption’.[1]Petechia refers to one of the three descriptive types of hematoma differentiated by size, the other twobeing ecchymosis and purpura. Ecchymosis is defined as hematomas larger than 1 centimetre and purpura as 1–5[1]millimetres.[2]The term is almost always used in the plural (petechiae), since a single lesion is seldom noticed or significant.https://en.wikipedia.org/wiki/PetechiaPulmonary embolism¹⁰Pulmonary embolism PE () is a blockage of an artery in the lungs by a substance that has moved from elsewhere inthe body through the bloodstream (embolism). Symptoms of a PE may include [6]shortness of breath chest, pain particularly upon breathing in, and coughing up blood. Symptoms of a [1]blood clot in the leg may also be present,such as a red, warm, swollen, and painful leg. Signs of a PE include low blood [1]oxygen levels rapid breathing rapid, , heart rate, and sometimes a mild fever.[11] Severe cases can lead to passing out abnormally low blood pressure, ,and sudden death.[2]PE usually results from a blood clot in the leg that travels to the lung. The risk of [6]blood clots is increased by cancer,prolonged bed rest smoking stroke, , , certain genetic conditions, estrogen-based medication pregnancy obesity, , , andafter some types of surgery. A small proportion of cases are due to the embolization of [3]air fat, , or amnioticfluid.[12][13] Diagnosis is based on signs and symptoms in combination with test results. If the risk is low, a blood test[4]known as a D-dimer may rule out the condition. Otherwise, a [4]CT pulmonary angiography lung ventilation/perfusion, scan, or ultrasound of the legs may confirm the diagnosis. Together, [4]deep vein thrombosis and PE are knownas venous thromboembolism (VTE).[14]Efforts to prevent PE include beginning to move as soon as possible after surgery, lower leg exercises during periodsof sitting, and the use of blood thinners after some types of surgery.[15] Treatment is with anticoagulants suchas heparin warfarin, or one of the direct-acting oral anticoagulants (DOACs). These are recommended for at least[5]three months. Severe cases may require [5]thrombolysis using medication such as tissue plasminogen activator (tPA)given intravenously or through a catheter, and some may require surgery (a pulmonary thrombectomy).[16] If bloodthinners are not appropriate, a temporary vena cava filter may be used.[16]Pulmonary emboli affect about 430,000 people each year in Europe. In the United States, between 300,000 and[8]600,000 cases occur each year,[6][7] which contribute to at least 40,000 deaths. Rates are similar in males and[9]females. They become more common as people get older.[3][3]https://en.wikipedia.org/wiki/Pulmonary_embolismPurpura¹¹Purpura (/ˈpɜːrpjʊərə/[1]) is a condition of red or purple discolored spots on the skin that do not blanch on applyingpressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders,coagulation disorders, or other causes. They measure 3–10 mm, whereas [2][3]petechiae measure less than 3 mm,and ecchymoses greater than 1 cm.[4]Purpura is common with typhus and can be present with meningitis caused by meningococci or septicaemia. Inparticular, meningococcus (Neisseria meningitidis), a Gram-negative diplococcus organism, releases endotoxin when itlyses. Endotoxin activates the Hageman factor (clotting factor XII), which causes disseminated intravascularcoagulation (DIC). The DIC is what appears as a rash on the affected individual.https://en.wikipedia.org/wiki/Purpura

Thrombocytopenia¹²Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, inthe blood. It is the most common [2]coagulation disorder among intensive care patients and is seen in 20% of medicalpatients and a third of surgical patients.[3]A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Values outside this[4]range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatmentis a platelet count below 50,000 per microliter. Thrombocytopenia can be contrasted with the conditions associated[5]with an abnormally high level of platelets in the blood: thrombocythemia (when the cause is unknown),and thrombocytosis (when the cause is known).[6][7]https://en.wikipedia.org/wiki/ThrombocytopeniaThrombosis¹³Thrombosis (from Ancient Greekθρόμβωσιςthrómbōsis \"clotting”) is the formation of a blood clot inside a bloodvessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) isinjured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a bloodvessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, thatbreaks free and begins to travel around the body is known as an embolus.[1][2]Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis leads tocongestion of the affected part of the body, while arterial thrombosis (and rarely severe venous thrombosis) affects theblood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either anarterial or a venous thrombus can break off as an embolus which can travel through the circulation and lodgesomewhere else as an embolism. This type of embolism is known as a thromboembolism. Complications can arisewhen a venous thromboembolism (commonly called a VTE) lodges in the lung as a pulmonary embolism. An arterialembolus may travel further down the affected blood vessel where it can lodge as an embolism.https://en.wikipedia.org/wiki/ThrombosisVasculitis¹⁴Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both [2]arteries and veins areaffected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is[3]primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins(phlebitis) or arteries (arteritis) on their own are separate entities.https://en.wikipedia.org/wiki/Vasculitis

Cerebral venous sinus thrombosisOthernamesCerebral venous and sinusthrombosis, (superior) sagittalsinus thrombosis, dural sinusthrombosis, intracranial venousthrombosis, cerebralthrombophlebitisDural veinsSpecialtyNeurologyTreatmentLow molecular weight heparin[1]Cerebral venous sinus thrombosisCerebral venous sinus thrombosis CVST (),cerebral venous and sinus thrombosis orcerebral venous thrombosis CVT (), is thepresence of a blood clot in the dural venoussinuses (which drain blood from the brain), thecerebral veins, or both. Symptoms may includesevere headache, visual symptoms, any of thesymptoms of stroke such as weakness of the faceand limbs on one side of the body, and seizures.The diagnosis is usually by computed tomography(CT scan) or magnetic resonance imaging (MRI) todemonstrate obstruction of the venous sinuses.[2]After confirmation of the diagnosis, investigationsmay be performed to determine the underlyingcause, especially if one is not readily apparent.Treatment is typically with anticoagulants(medications that suppress blood clotting) such aslow molecular weight heparin. [1]Rarely,thrombolysis (enzymatic destruction of the bloodclot) is used. The disease may be complicated byraised intracranial pressure, which may warrantsurgical intervention such as the placement of ashunt.[2]Signs and symptomsCausesDiagnosisImagingD-dimerFurther testsPathogenesisTreatmentPrognosisEpidemiologyHistoryCOVID-19 vaccineNotable casesReferencesContents

External linksNine in ten people with cerebral venous thrombosis have a headache; this tends to worsen overthe period of several days, but may also develop suddenly (thunderclap headache).[2] Theheadache may be the only symptom.[3] Many have symptoms of stroke: inability to move one ormore limbs, weakness on one side of the face or difficulty speaking. The neurologic deficitsrelated to central venous thromboses does not necessarily affect one side of the body or onearterial or brain territory as is more common \"arterial\" strokes.[2][4] Bilateral 6th cranial nervepalsies may occur, causing abnormalities related to eye movement, but this is rare.[4]40% of people have seizures, although it is more common in women who develop sinusthrombosis peripartum (in the period before and after giving birth).[5] These are mostly seizuresaffecting only one part of the body and unilateral (occurring on one side), but occasionally theseizures are generalised and rarely they lead to status epilepticus (persistent or recurrent seizureactivity for a long period of time).[2]In the elderly, many of the aforementioned symptoms may not occur. Common symptoms in theelderly with this condition are otherwise unexplained changes in mental status and a depressedlevel of consciousness.[6]The pressure around the brain may rise, causing papilledema (swelling of the optic disc) whichmay be experienced as visual obscurations. In severely raised intracranial pressure, the level ofconsciousness is decreased, the blood pressure rises, the heart rate falls and there is abnormalposturing.[2]Focal neurologic deficits may occur hours to days after the headache in 50% of cases, this maypresent as hemiparesis (unilateral weakness) if due to infarction of the frontal or parietal lobewhich are drained by the vein of Trolard. Focal deficits may also present as aphasia or confusionif the vein of Labbe (responsible for draining the temporal lobe) is affected.[4]Disorders that cause, or increase the risk for systemic venous thrombosis are associated withcentral venous thromboses.[4] In children, head and neck infections and acute systemic illnessesare the primary cause of central venous thrombosis.[4] Cerebral venous sinus thrombosis is morecommon in particular situations. 85% of people have at least one of these risk factors:[2]Thrombophilia, a tendency to develop blood clots due to abnormalities in coagulation, e.g.factor V Leiden, deficiency of protein C, protein S or antithrombin, or related problemsNephrotic syndrome, a kidney problem causing protein loss in the urineChronic inflammatory diseases, such as inflammatory bowel disease, lupus and Behçet'sdiseasePregnancy and puerperium (the period after giving birth)Particular blood disorders, especially polycythemia vera and paroxysmal nocturnalhemoglobinuriaUse of estrogen-containing forms of hormonal contraceptionMeningitis and infections of the ear, nose and throat area such as mastoiditis and sinusitisDirect injury to the venous sinusesMedical procedures in the head and neck areaSigns and symptomsCauses

CT venogram showing a fillingdefect in the sagittal sinus (blackarrow)Sickle cell anemiaDehydration, primarily in infants and childrenHomocysteinemiaHomocystinuriaCOVID-19: Cases of CVST have been reported in patients with COVID-19 in the absence ofthe aforementioned risk factors.[7]The diagnosis may be suspected on the basis of the symptoms, for example the combination ofheadache, signs of raised intracranial pressure and focal neurological abnormalities, or whenalternative causes of headache and neurological abnormalities, such as a subarachnoidhemorrhage, have been excluded.[2]There are various neuroimaging investigations that maydetect cerebral sinus thrombosis. Cerebral edema andvenous infarction may be apparent on any modality, but forthe detection of the thrombus itself, the most commonlyused tests are computed tomography (CT) and magneticresonance imaging (MRI), both using various types ofradiocontrast to perform a venogram and visualise the veinsaround the brain.[2]Computed tomography, with radiocontrast in the venousphase (CT venography or CTV), has a detection rate that insome regards exceeds that of MRI. The test involvesinjection into a vein (usually in the arm) of a radioopaquesubstance, and time is allowed for the bloodstream to carry itto the cerebral veins – at which point the scan is performed.It has a sensitivity of 75–100% (it detects 75–100% of allclots present), and a specificity of 81–100% (it would beincorrectly positive in 0–19%). In the first two weeks, the\"empty delta sign\" may be observed (in later stages, this signmay disappear).[8] The empty delta sign is characterized by enhancement of the dural wallwithout intra-sinus enhancement.[4]Magnetic resonance venography employs the same principles, but uses MRI as a scanningmodality. MRI has the advantage of being better at detecting damage to the brain itself as aresult of the increased pressure on the obstructed veins, but it is not readily available in manyhospitals and the interpretation may be difficult.[8]Cerebral angiography may demonstrate smaller clots than CT or MRI, and obstructed veins maygive the \"corkscrew appearance\".[2] This, however, requires puncture of the femoral artery with asheath and advancing a thin tube through the blood vessels to the brain where radiocontrast isinjected before X-ray images are obtained. It is therefore only performed if all other tests giveunclear results or when other treatments may be administered during the same procedure.DiagnosisImagingD-dimer

A dural venous sinus thrombosis ofthe transverse sinus. Greater on theright than left.There is an association between the D-dimer blood test andcerebral venous sinus thrombosis.[9] This associationhowever is not strong enough to rule out the diagnosisalone.[9]In most cases, the direct cause for the cerebral sinusthrombosis is not readily apparent. Identifying a source ofinfection is crucial; it is common practice to screen forvarious forms of thrombophilia (a propensity to form bloodclots).[2]The veins of the brain, both the superficial veins and thedeep venous system, empty into the dural venous sinuses,which carry blood back to the jugular vein and thence to theheart. In cerebral venous thrombosis, blood clots usuallyform both in the veins of the brain and the venous sinuses. The thrombosis of the veinsthemselves causes venous infarction (damage to brain tissue due to a congested and thereforeinsufficient blood supply). This results in cerebral edema (both vasogenic and cytotoxic edema),and leads to small petechial haemorrhages that may merge into large haematomas. Thrombosisof the sinuses is the main mechanism behind the increase in intracranial pressure due todecreased resorption of cerebrospinal fluid (CSF). The condition does not typically lead tohydrocephalus, however, because there is no difference in pressure between various parts of thebrain.[2]Any blood clot forms due to an imbalance between coagulation (the formation of the insolubleblood protein fibrin) and fibrinolysis. The three major mechanisms for such an imbalance areenumerated in Virchow's triad: alterations in normal blood flow, injury to the blood vessel wall,and alterations in the constitution of blood (hypercoagulability). Most cases of cerebral venoussinus thrombosis are due to hypercoagulability.[2] The inflammatory response and prolongedimmobilization of patients with COVID-19 may also help explain the formation of CVST.[7]It is possible for the clot to break off and migrate (embolise) to the lungs, causing a pulmonaryembolism.[2][5] An analysis of earlier case reports concludes that this occurs in about 10% ofcases, but has a very poor prognosis.[10]Central venous thromboses usually involve the dural sinuses with or without involvement of thecortical veins; isolated cortical venous thromboses are extremely rare with only about 100 casesreported.[4]Various studies have investigated the use of anticoagulation to suppress blood clot formation incerebral venous sinus thrombosis. Before these trials had been conducted, there had been aconcern that small areas of hemorrhage in the brain would bleed further as a result of treatment;the studies showed that this concern was unfounded.[11] Clinical practice guidelines nowrecommend heparin or low molecular weight heparin in the initial treatment, followed bywarfarin, provided there are no other bleeding risks that would make these treatmentsunsuitable.[5][12][13] Some experts discourage the use of anticoagulation if there is extensiveFurther testsPathogenesisTreatment

hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If thehemorrhage has decreased in size, anticoagulants are started, while no anticoagulants are givenif there is no reduction.[14]The duration of warfarin treatment depends on the circumstances and underlying causes of thecondition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), threemonths are regarded as sufficient. If the condition was unprovoked but there are no clear causesor a \"mild\" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlyingthrombosis disorder, warfarin treatment may need to continue indefinitely.[5]Heparin and platelet transfusions should not be used as a treatment for any form of cerebralvenous thrombosis caused by immune thrombotic thrombocytopenias including Heparininduced thrombocytopenia (HIT), auto-immune heparin induced thrombocytopenia (aHIT) orvaccine induced immune thrombotic thrombocytopenia (VITT) due to unpredictable effects ofheparin on anti-platelet factor-4 antibodies (PF-4). In cases of VITT, intra-venous immuneglobulins (IVIG) are recommended as they block the anti-PF4 antibody interaction with plateletsand a non-heparin anticoagulant. In refractory cases, plasma exchange may be used.[4]Thrombolysis (removal of the blood clot with \"clot buster\" medication) has been described,either systemically by injection into a vein or directly into the clot during angiography. The 2006European Federation of Neurological Societies guideline recommends that thrombolysis is onlyused in people who deteriorate despite adequate treatment, and other causes of deteriorationhave been eliminated. It is unclear which drug and which mode of administration is the mosteffective. Bleeding into the brain and in other sites of the body is a major concern in the use ofthrombolysis.[5] American guidelines make no recommendation with regards to thrombolysis,stating that more research is needed.[13]In those where a venous infarct or hemorrhage causes significant compression of surroundingbrain structures, decompressive craniectomy is sometimes required.[15] Raised intracranialpressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal ofexcessive cerebrospinal fluid), or neurosurgical treatment (optic nerve sheath fenestration orshunting).[2] Venous stenting is emerging as a minimally invasive, safer alternative toshunting.[16] In certain situations, anticonvulsants may be used to try to prevent seizures.[5]These situations include focal neurological problems (e.g. inability to move a limb) and focalchanges of the brain tissue on CT or MRI scan.[5] Evidence to support or refute the use ofantiepileptic drugs as a preventive measure, however, is lacking.[17]In 2004 the first adequately large scale study on the natural history and long-term prognosis ofthis condition was reported; this showed that at 16 months follow-up 57.1% of people had fullrecovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms orimpairments, and 8.3% had died. Severe impairment or death were more likely in those agedover 37 years, male, affected by coma, mental status disorder, intracerebral hemorrhage,thrombosis of the deep cerebral venous system, central nervous system infection and cancer.[18]A subsequent systematic review of nineteen studies in 2006 showed that mortality is about 5.6%during hospitalisation and 9.4% in total, while of the survivors 88% make a total or near-totalrecovery. After several months, two thirds of the cases has resolution (\"recanalisation\") of theclot. The rate of recurrence was low (2.8%).[19]In children with CVST the risk of death is high.[20] Poor outcome is more likely if a child withCVST develops seizures or has evidence of venous infarction on imaging.[21]Prognosis

Cerebral venous sinus thrombosis is rare, with an estimated 3-4 cases per million annualincidence in adults. While it may occur in all age groups, it is most common in the third decade.75% are female.[5] Given that older studies show no difference in incidence between men andwomen, it has been suggested that the use of oral contraceptives in women is behind thedisparity between the sexes.[2] A 1995 report from Saudi Arabia found a substantially largerincidence at 7 cases per 100,000; this was attributed to the fact that Behçet's disease, whichincreases risk of CVST, is more common in the Middle East.[22]A 1973 report found that CVST could be found on autopsy (examination of the body after death)in nine percent of all people. Many of these were elderly and had neurological symptoms in theperiod leading up to their death, and many suffered from concomitant heart failure.[23] Anestimated 0.3% incidence of CVST in patients infected with SARS-CoV-2.[7]In children, a Canadian study reported in 2001 that CVST occurs in 6.7 per million annually.43% occur in the newborn (less than one month old), and a further 10% in the first year of life. Ofthe newborn, 84% were already ill, mostly from complications after childbirth anddehydration.[21]The first description of thrombosis of the cerebral veins and sinuses is attributed to the Frenchphysician Ribes, who in 1825 observed thrombosis of the sagittal sinus and cerebral veins in aman who had suffered from seizures and delirium.[24] Until the second half of the 20th century itremained a diagnosis generally made after death.[25] In the 1940s, reports by Dr CharlesSymonds and others allowed for the clinical diagnosis of cerebral venous thrombosis, usingcharacteristic signs and symptoms and results of lumbar puncture.[26][27]Improvements on the diagnosis of cerebral venous sinus thrombosis in life were made with theintroduction of venography in 1951,[28] which also aided in the distinction from idiopathicintracranial hypertension,[29] which has similar presenting signs and symptoms in manycases.[25]The British gynecologist Stansfield is credited with the introduction, in 1942, of the just recentlyintroduced anticoagulant heparin in the treatment of CVST in 1942.[25][27] Clinical trials in the1990s finally resolved the concern about using anticoagulants in most cases of CVST.[5]In March 2021, the European Medicines Agency (EMA) announced that out of the around 20million people who had received the Oxford–AstraZeneca COVID-19 vaccine, general bloodclotting rates were normal, but that it had identified seven cases of disseminated intravascularcoagulation, and eighteen cases of cerebral venous sinus thrombosis.[30] A causal link with thevaccine had not been proven, but the EMA decided to conduct further analysis and to informrecipients of the remote possibility of such rare syndromes.[30] EMA confirmed that the vaccine'sbenefits still outweigh the risks[30] and later released updated product information.[31][32][33]The British Medicines and Healthcare products Regulatory Agency (MHRA) confirmed 79 casesof thrombosis, including 19 fatalities, within the first 20 million vaccinations in Great Britain.[34] [35] Guidelines on management of suspected cases was issued by the British Society forHaematology; it discouraged the use of heparin until it was clearer that heparin would notaggravate the thrombosis.[36] On 13 April 2021 the Centers for Disease Control and PreventionEpidemiologyHistoryCOVID-19 vaccine

paused the use of the Janssen COVID-19 vaccine in the United States due to six cases of CVSTthat occurred 6 to 13 days after administration.[37] The recommended pause was lifted on 23April 2021 following a safety review. [38]U.S. Secretary of State Hillary Clinton was hospitalized on December 30, 2012, foranticoagulation treatment of venous thrombosis of the right transverse sinus, which is located atthe base of the brain. Clinton's thrombotic episode was discovered on an MRI scan done forfollow-up of a cerebral concussion she had suffered 2.5 weeks previously, when she fell whilesuffering from gastroenteritis.[39]1. Al Rawahi, B; Almegren, M; Carrier, M (September 2018). \"The efficacy and safety ofanticoagulation in cerebral vein thrombosis: A systematic review and meta-analysis\".Thrombosis Research. 169: 135–139. doi 10.1016/j.thromres.2018.07.023 (https://doi.org/10.:1016%2Fj.thromres.2018.07.023) PMID 30056293 (https://pubmed.ncbi.nlm.nih.gov/300562. 93).2. Stam J (2005). \"Thrombosis of the cerebral veins and sinuses\" (http://dare.uva.nl/personal/pure/en/publications/thrombosis-of-the-cerebral-veins-and-sinuses(86f1380e-2fad-4435-8086-29c69dec3300).html). N. Engl. J. Med. 352 (17): 1791–8. doi 10.1056/NEJMra042354 (http:s://doi.org/10.1056%2FNEJMra042354) PMID 15858188 (https://pubmed.ncbi.nlm.nih.gov/1. 5858188).3. Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG (2005). \"Headache as the onlyneurological sign of cerebral venous thrombosis: a series of 17 cases\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739763). J. Neurol. Neurosurg. Psychiatry. 76 (8): 1084–7.doi 10.1136/jnnp.2004.056275 (https://doi.org/10.1136%2Fjnnp.2004.056275):.PMC 1739763 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739763) PMID 16024884 (ht. tps://pubmed.ncbi.nlm.nih.gov/16024884).4. Ropper, Allan H.; Klein, Joshua P. (1 July 2021). \"Cerebral Venous Thrombosis\". NewEngland Journal of Medicine. 385 (1): 59–64. doi 10.1056/NEJMra2106545 (https://doi.org/1:0.1056%2FNEJMra2106545).5. Einhäupl K, Bousser MG, de Bruijn SF, et al. (2006). \"EFNS guideline on the treatment ofcerebral venous and sinus thrombosis\". Eur. J. Neurol. 13 (6): 553–9. doi 10.1111/j.1468-:1331.2006.01398.x (https://doi.org/10.1111%2Fj.1468-1331.2006.01398.x) PMID 16796579. (https://pubmed.ncbi.nlm.nih.gov/16796579) S2CID 17618264 (https://api.semanticscholar.o. rg/CorpusID:17618264).6. Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F (2005). \"Cerebral vein anddural sinus thrombosis in elderly patients\" (https://doi.org/10.1161%2F01.STR.0000177894.05495.54). Stroke. 36 (9): 1927–32. doi 10.1161/01.STR.0000177894.05495.54 (https://doi.or:g/10.1161%2F01.STR.0000177894.05495.54) PMID 16100024 (https://pubmed.ncbi.nlm.ni. h.gov/16100024).7. Gutiérrez-Zevallos, JD; Guarniz-Huamán, DA; Sánchez-Landers., M. \"Cerebral venousthrombosis and COVID-19: A silent killer during the pandemic?\" (https://revistas.upch.edu.pe/index.php/RNP/article/view/3933/4480). Revista de Neuro-Psiquiatria. 84 (1): 19–24.doi 10.20453/rnp.v84i1.3933 (https://doi.org/10.20453%2Frnp.v84i1.3933):.8. Smith R, Hourihan MD (2007). \"Investigating suspected cerebral venous thrombosis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852020). BMJ. 334 (7597): 794–5.doi 10.1136/bmj.39154.636968.47 (https://doi.org/10.1136%2Fbmj.39154.636968.47):.PMC 1852020 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852020) PMID 17431266 (ht. tps://pubmed.ncbi.nlm.nih.gov/17431266).Notable casesReferences

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18. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F (2004). \"Prognosis ofcerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Veinand Dural Sinus Thrombosis (ISCVT)\" (https://doi.org/10.1161%2F01.STR.0000117571.76197.26). Stroke. 35 (3): 664–70. doi 10.1161/01.STR.0000117571.76197.26 (https://doi.org/10.1:161%2F01.STR.0000117571.76197.26) PMID 14976332 (https://pubmed.ncbi.nlm.nih.gov/1. 4976332).19. Dentali F, Gianni M, Crowther MA, Ageno W (2006). \"Natural history of cerebral veinthrombosis: a systematic review\" (https://doi.org/10.1182%2Fblood-2005-12-4795). Blood.108 (4): 1129–34. doi 10.1182/blood-2005-12-4795 (https://doi.org/10.1182%2Fblood-2005-1:2-4795) PMID 16609071 (https://pubmed.ncbi.nlm.nih.gov/16609071). .20. Jackson, BF; Porcher, FK; Zapton, DT; Losek, JD (September 2011). \"Cerebral sinovenousthrombosis in children: diagnosis and treatment\". Pediatr. Emerg. Care. 27 (9): 874–80, quiz881–3. doi 10.1097/PEC.0b013e31822c9ccc (https://doi.org/10.1097%2FPEC.0b013e31822:c9ccc) PMID 21926891 (https://pubmed.ncbi.nlm.nih.gov/21926891) S2CID 11390572 (http. . s://api.semanticscholar.org/CorpusID:11390572).21. deVeber G, Andrew M, Adams C, et al. (August 2001). \"Cerebral sinovenous thrombosis inchildren\". N. Engl. J. Med. 345 (6): 417–23. doi 10.1056/NEJM200108093450604 (https://do:i.org/10.1056%2FNEJM200108093450604) PMID 11496852 (https://pubmed.ncbi.nlm.nih.g. ov/11496852).22. Daif A, Awada A, al-Rajeh S, et al. (1 July 1995). \"Cerebral venous thrombosis in adults. Astudy of 40 cases from Saudi Arabia\". Stroke. 26 (7): 1193–5. doi 10.1161/01.str.26.7.1193 (h:ttps://doi.org/10.1161%2F01.str.26.7.1193) PMID 7604412 (https://pubmed.ncbi.nlm.nih.gov/. 7604412).23. Towbin A (1 May 1973). \"The syndrome of latent cerebral venous thrombosis: its frequencyand relation to age and congestive heart failure\" (https://doi.org/10.1161%2F01.str.4.3.419).Stroke. (3): 419–30. 4doi 10.1161/01.str.4.3.419 (https://doi.org/10.1161%2F01.str.4.3.419):.PMID 4713031 (https://pubmed.ncbi.nlm.nih.gov/4713031).24. Ribes MF (1825). \"Des recherches faites sur la phlebite\". Rev. Med. Fr. Etrang. : 5–41.325. Bousser MG, Chiras J, Bories J, Castaigne P (1 March 1985). \"Cerebral venous thrombosis—a review of 38 cases\" (https://doi.org/10.1161%2F01.str.16.2.199). Stroke. 16 (2): 199–213. doi 10.1161/01.str.16.2.199 (https://doi.org/10.1161%2F01.str.16.2.199) PMID 3975957:. (https://pubmed.ncbi.nlm.nih.gov/3975957).26. Symonds CP (September 1940). \"Cerebral thrombophlebitis\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2179068). Br. Med. J. (4158): 348–52. 2doi 10.1136/bmj.2.4158.348 (http:s://doi.org/10.1136%2Fbmj.2.4158.348) PMC 2179068 (https://www.ncbi.nlm.nih.gov/pmc/ar. ticles/PMC2179068) PMID 20783290 (https://pubmed.ncbi.nlm.nih.gov/20783290). .27. Stansfield FR (April 1942). \"Puerperal cerebral thrombophlebitis treated by heparin\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2164893). Br. Med. J. (4239): 436–438.1doi 10.1136/bmj.1.4239.436 (https://doi.org/10.1136%2Fbmj.1.4239.436) PMC 2164893 (htt:. ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2164893) PMID 20784169 (https://pubmed.ncb. i.nlm.nih.gov/20784169).28. Ray BS, Dunbar HS, Dotter CT (January 1951). \"Dural sinus venography as an aid todiagnosis in intracranial disease\". J. Neurosurg. (1): 23–37. 8doi 10.3171/jns.1951.8.1.0023:(https://doi.org/10.3171%2Fjns.1951.8.1.0023) PMID 14804146 (https://pubmed.ncbi.nlm.ni. h.gov/14804146).29. Ray BS, Dunbar HS (September 1951). \"Thrombosis of the dural venous sinuses as a causeof pseudotumor cerebri\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1802934). Ann.Surg. 134 (3): 376–86. doi 10.1097/00000658-195113430-00009 (https://doi.org/10.1097%2:F00000658-195113430-00009) PMC 1802934 (https://www.ncbi.nlm.nih.gov/pmc/articles/P. MC1802934) PMID 14869026 (https://pubmed.ncbi.nlm.nih.gov/14869026). .30. \"COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rareblood clots with low blood platelets\" (https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots). EuropeanMedicines Agency (EMA) (Press release). 18 March 2021. Retrieved 18 March 2021.

Classification ICD-10: G08 (https://icd.who.int/browse10/2019/en#/G08), I63.6 (https://icd.who.int/browse10/2019/en#/I63.6),I67.6 (https://icd.who.int/browse10/2019/en#/I67.6) · ICD-9-CM: 325 (http://www.icd9data.com/getICD9Code.ashx?icd9=325), 437.6 (http://www.icd9data.com/getICD9Code.ashx?icd9=437.6) ·MeSH: D012851 (ht\"Intracranial venous thrombosis – Patient UK\" (http://www.patient.co.uk/showdoc/40000819/).UCH Institute for Child Health. \"Clinical guideline CerebralVenous Sinus Thrombosis in Children\" (https://web.archive.org/web/20090202042805/http://www.ich.ucl.ac.uk/clinical_information/clinical_guidelines/cmg_guideline_00037).Archived from the original (http://www.ich.ucl.ac.uk/clinical_information/clinical_guidelines/cmg_guideline_00037) on 2February 2009. Retrieved 28 October 2007.31. \"COVID-19 Vaccine AstraZeneca – Update on ongoing evaluation of blood clot cases\" (https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-update-ongoing-evaluation-blood-clot-cases). European Medicines Agency (EMA) (Press release). 25 March 2021.Retrieved 25 March 2021.32. \"Annex 1: Summary of Product Characteristics\" (https://www.ema.europa.eu/documents/product-information/vaxzevria-previously-covid-19-vaccine-astrazeneca-epar-product-information_en.pdf) (PDF). European Medicines Agency (EMA). Retrieved 29 March 2021.33. \"COVID-19 Vaccine AstraZeneca: Risk of thrombocytopenia and coagulation disorders\" (https://www.ema.europa.eu/en/medicines/dhpc/covid-19-vaccine-astrazeneca-risk-thrombocytopenia-coagulation-disorders). European Medicines Agency (EMA). 24 March 2021. Retrieved25 March 2021.34. [1] (https://www.gov.uk/government/news/mhra-issues-new-advice-concluding-a-possible-link-between-covid-19-vaccine-astrazeneca-and-extremely-rare-unlikely-to-occur-blood-clots)35. \"Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought\" (https://www.gov.uk/government/news/mhra-issues-new-advice-concluding-a-possible-link-between-covid-19-vaccine-astrazeneca-and-extremely-rare-unlikely-to-occur-blood-clots). The BritishGovernment (gov.uk) (Press release). 7 April 2021. Retrieved 8 April 2021.36. Expert Haematology Panel (7 April 2021). \"Guidance produced from the Expert HaematologyPanel (EHP) focussed on Covid-19 Vaccine induced Thrombosis and Thrombocytopenia(VITT)\" (https://b-s-h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-c-19-vaccine_20210407.pdf) (PDF). BSH.org.uk. BritishSociety for Haematology. Retrieved 29 April 2021.37. Marks, Peter. \"Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine\" (https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine). Retrieved 13 April 2021.38. \"FDA and CDC Lift Recommended Pause on Johnson & Johnson (Janssen) COVID-19Vaccine Use Following Thorough Safety Review\" (https://www.cdc.gov/media/releases/2021/fda-cdc-lift-vaccine-use.html). Retrieved 18 June 2021.39. Paul Richter. \"Hillary Clinton expected to make full recovery from blood clot\" (http://www.latimes.com/news/politics/la-pn-hillary-clinton-blood-clot-recovery-20121231,0,2962900.story).Los Angeles Times. Retrieved 1 January 2013.External linksD

tps://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D012851) ·DiseasesDB: 2242(http://www.diseasesdatabase.com/ddb2242.htm)ExternalresourceseMedicine:neuro/642 (https://emedicine.medscape.com/neuro/642-overview) radio/105 (http://www.emedicine.com/radio/topic105.htm#)Retrieved from \"https://en.wikipedia.org/w/index.php?title=Cerebral_venous_sinus_thrombosis&oldid=1040193119\"This page was last edited on 23 August 2021, at 04:21 (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.

CoagulopathyOther namesBleeding disorderPlateletsSpecialtyHematology CoagulopathyCoagulopathy(also called a bleedingdisorder) is a condition in which the blood'sability to coagulate (form clots) is impaired. This[1]condition can cause a tendency toward prolongedor excessive bleeding (bleeding diathesis), whichmay occur spontaneously or following an injury ormedical and dental procedures.Of note, coagulopathies are sometimeserroneously referred to as \"clotting disorders\"; aclotting disorder is a predisposition to clotformation (thrombus), also known as ahypercoagulable state or thrombophilia.Signs and symptomsMechanismAcute traumatic coagulopathyTreatmentCritical careSee alsoReferencesCoagulopathy may cause uncontrolled internal or external bleeding. Left untreated, uncontrolledbleeding may cause damage to joints, muscles, or internal organs and may be life-threatening.People should seek immediate medical care for serious symptoms, including heavy externalbleeding, blood in the urine or stool, double vision, severe head or neck pain, repeated vomiting,difficulty walking, convulsions, or seizures. They should seek prompt medical care if theyexperience mild but unstoppable external bleeding or joint swelling and stiffness.The normal clotting process depends on the interplay of various proteins in the blood.Coagulopathy may be caused by reduced levels or absence of blood-clotting proteins, known asclotting factors or coagulation factors. Genetic disorders, such as hemophilia and VonWillebrand disease, can cause a reduction in clotting factors.[2]Anticoagulants such as warfarin will also prevent clots from forming properly.[2] Coagulopathymay also occur as a result of dysfunction or reduced levels of platelets (small disk-shaped bodiesin the bloodstream that aid in the clotting process).ContentsSigns and symptomsMechanism

In 2003, Karim Brohi, Professor of Trauma Sciences at Queen Mary University of London, firstintroduced the term Acute Traumatic Coagulopathy (ATC),[3] establishing that coagulopathyinduced by trauma results in:more severe bleedingmulti-organ failurehigh mortalityIf someone has coagulopathy, their health care provider may help them manage their symptomswith medications or replacement therapy. In replacement therapy, the reduced or absent clottingfactors are replaced with proteins derived from human blood or created in the laboratory. Thistherapy may be given either to treat bleeding that has already begun or to prevent bleeding fromoccurring.One area of treatment is managing people with major bleeding in a critical setting, like anemergency department. In these situations, the common treatment is transfusing a[1]combination of red cells with one of the following options:Blood plasmaProthrombin complex concentrate, factor XIII, and fibrinogenFibrinogen with tranexamic acidThe use of tranexamic acid is the only option that is currently supported by a large, randomized,controlled clinical trial, and is given to people with major bleeding after trauma.[4] There areseveral possible risks to treating coagulopathies, such as transfusion-related acute lung injury,acute respiratory distress syndrome, multiple organ dysfunction syndrome, major hemorrhage,and venous thromboembolism.Acute traumatic coagulopathyTreatmentCritical care

Laboratory findings in various platelet and coagulation disordersConditionProthrombintimePartialthromboplastintimeBleedingtimePlatelet countVitamin K deficiency or warfarinProlongedNormal or mildlyprolongedUnaffectedUnaffectedDisseminated intravascularcoagulationProlongedProlongedProlongedDecreasedVon Willebrand diseaseUnaffectedProlonged orunaffectedProlongedUnaffectedHemophiliaUnaffectedProlongedUnaffectedUnaffectedAspirinUnaffectedUnaffectedProlongedUnaffectedThrombocytopeniaUnaffectedUnaffectedProlongedDecreasedLiver failure, earlyProlongedUnaffectedUnaffectedUnaffectedLiver failure, end-stageProlongedProlongedProlongedDecreasedUremiaUnaffectedUnaffectedProlongedUnaffectedCongenital afibrinogenemiaProlongedProlongedProlongedUnaffectedFactor V deficiencyProlongedProlongedUnaffectedUnaffectedFactor X deficiency as seen inamyloid purpuraProlongedProlongedUnaffectedUnaffectedGlanzmann's thrombastheniaUnaffectedUnaffectedProlongedUnaffectedBernard–Soulier syndromeUnaffectedUnaffectedProlongedDecreased orunaffectedFactor XII deficiencyUnaffectedProlongedUnaffectedUnaffectedC1INH deficiencyUnaffectedShortenedUnaffectedUnaffectedTrauma triad of deathHypocoagulabilityHypercoagulability1. Hunt, Beverley J. (2014). \"Bleeding and Coagulopathies in Critical Care\". New EnglandJournal of Medicine. 370 (9): 847–859. doi 10.1056/NEJMra1208626 (https://doi.org/10.105:6%2FNEJMra1208626) ISSN 0028-4793 (https://www.worldcat.org/issn/0028-4793). .PMID 24571757 (https://pubmed.ncbi.nlm.nih.gov/24571757).2. Spahn, DR.; Bouillon, B.; Cerny, V.; Coats, TJ.; Duranteau, J.; Fernández-Mondéjar, E.;Filipescu, D.; Hunt, BJ.; et al. (Apr 2013). \"Management of bleeding and coagulopathyfollowing major trauma: an updated European guideline\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056078). Crit Care. 17 (2): R76. doi 10.1186/cc12685 (https://doi.org/10.1186%2:Fcc12685) PMC 4056078 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056078). .PMID 23601765 (https://pubmed.ncbi.nlm.nih.gov/23601765).3. Brohi, Karim; Singh, Jasmin; Heron, Mischa; Coats, Timothy (June 2003). \"Acute TraumaticCoagulopathy\" (http://insights.ovid.com/). The Journal of Trauma: Injury, Infection, andCritical Care. 54 (6): 1127–1130. doi 10.1097/01.TA.0000069184.82147.06 (https://doi.org/1:See alsoReferences

Classification ICD-10: D65 (https://icd.who.int/browse10/2019/en#/D65)-D68 (https://icd.who.int/browse10/2019/en#/D68) ·ICD-9-CM: 286 (http://www.icd9data.com/getICD9Code.ashx?icd9=286) ·MeSH: D001778 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D001778) ·DiseasesDB:29158 (http://www.diseasesdatabase.com/ddb29158.htm)0.1097%2F01.TA.0000069184.82147.06) ISSN 0022-5282 (https://www.worldcat.org/issn/00. 22-5282) PMID 12813333 (https://pubmed.ncbi.nlm.nih.gov/12813333). .4. Shakur, Haleema; Roberts, Ian; Perel, Pablo (2010). \"Tranexamic acid for trauma – Authors'reply\". The Lancet. 376 (9746): 1050–1051. doi 10.1016/S0140-6736(10)61479-1 (https://do:i.org/10.1016%2FS0140-6736%2810%2961479-1) ISSN 0140-6736 (https://www.worldcat.o. rg/issn/0140-6736).Retrieved from \"https://en.wikipedia.org/w/index.php?title=Coagulopathy&oldid=1009864350\"This page was last edited on 2 March 2021, at 17:46 (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.D

Deep vein thrombosisOther namesDeep venous thrombosisDVT in the right leg with swelling and rednessSpecialtyVariousSymptomsPain, swelling, redness,enlarged veins in the affectedlimb[1]ComplicationsPost-thrombotic syndrome,recurrent VTE[2]Risk factorsRecent surgery, older age,active cancer, obesity,infection, inflammatorydiseases, antiphospholipidsyndrome, personal history orfamily history of VTE, injuries,trauma, lack of movement,hormonal birth control,pregnancy and the periodDeep vein thrombosisDeep vein thrombosis DVT () is the formationof a blood clot in a deep vein, most commonly inthe legs or pelvis.[9][a] A minority of DVTs occur inthe arms.[11] Symptoms can include pain, swelling,redness, and enlarged veins in the affected area,but some DVTs have no symptoms. The most[1]common life-threatening concern with DVT is thepotential for a clot to embolize (detach from theveins), travel as an embolus through the right sideof the heart, and become lodged in a pulmonaryartery that supplies blood to the lungs. This iscalled a pulmonary embolism (PE). DVT and PEcomprise the cardiovascular disease of venousthromboembolism (VTE).[2] About two-thirds ofVTE manifests as DVT only, with one-thirdmanifesting as PE with or without DVT.[12] Themost frequent long-term DVT complication ispost-thrombotic syndrome, which can cause pain,swelling, a sensation of heaviness, itching, and insevere cases, ulcers.[5] Recurrent VTE occurs inabout 30% of those in the ten years following aninitial VTE.[3]The mechanism behind DVT formation typicallyinvolves some combination of decreased bloodflow, increased tendency to clot, changes to theblood vessel wall, and inflammation.[13] Riskfactors include recent surgery, older age, activecancer, obesity, infection, inflammatory diseases,antiphospholipid syndrome, personal history andfamily history of VTE, trauma, injuries, lack ofmovement, hormonal birth control, pregnancy,and the period following birth. VTE has a stronggenetic component, accounting for approximately50 to 60% of the variability in VTE rates.[4]Genetic factors include non-O blood type,deficiencies of antithrombin, protein C, andprotein S and the mutations of factor V Leiden andprothrombin G20210A. In total, dozens of geneticrisk factors have been identified.[4][14]People suspected of having DVT can be assessedusing a prediction rule such as the Wells score. AD-dimer test can also be used to assist withexcluding the diagnosis or to signal a need forfurther testing.[5] Diagnosis is most commonlyconfirmed by ultrasound of the suspected veins.[5]

following delivery, geneticfactors[3][4]DiagnosticmethodUltrasound[5]DifferentialdiagnosisCellulitis, ruptured Baker'scyst, hematoma, lymphedema,chronic venous insufficiency,etc.PreventionFrequent walking, calfexercises, maintaining ahealthy body weight,anticoagulants (bloodthinners), intermittentpneumatic compression,graduated compressionstockings, aspirin[6][7]TreatmentAnticoagulation, catheter-directed thrombolysisMedicationDirect oral anticoagulants,low-molecular-weight heparin,fondaparinux, unfractionatedheparin, warfarinFrequencyFrom 0.8–2.7 per 1000 peopleper year, but populations inChina and Korea are belowthis range[8]VTE becomes much more common with age. Thecondition is rare in children, but occurs in almost1% of those ≥ age 85 annually.[3] Asian, Asian-American, Native American, and Hispanicindividuals have a lower VTE risk than Whites orBlacks.[4][15] Populations in Asia have VTE rates at15 to 20% of what is seen in Western countries.[16]Using blood thinners is the standard treatment.Typical medications include rivaroxaban,apixaban, and warfarin. Beginning warfarintreatment requires an additional non-oralanticoagulant, often injections ofheparin.[17][18][19] Prevention of VTE for thegeneral population includes avoiding obesity andmaintaining an active lifestyle. Preventive effortsfollowing low-risk surgery include early andfrequent walking. Riskier surgeries generallyprevent VTE with a blood thinner or aspirincombined with intermittent pneumaticcompression.[7]Signs and symptomsAcute complicationsDifferential diagnosisClassificationCausesPathophysiologyDiagnosisManagementInvestigations for cancerInterventionsField of medicinePreventionHospital (non-surgical) patientsAfter surgeryPregnancyTravelersPrognosisEpidemiologySocialHistoryEconomicsResearch directionsNotesContents

Swelling from fluid (edema) canresult in \"pitting\" after pressure isapplied. If this occurs only on oneside, it raises the likelihood of DVT.ReferencesSymptoms classically affect a leg and typically develop overhours or days,[20] though they can develop suddenly or overa matter of weeks.[21] The legs are primarily affected, with4–10% of DVT occurring in the arms.[11] Despite the signsand symptoms being highly variable,[5] the typical symptomsare pain, swelling, and redness. However, these symptomsmight not manifest in the lower limbs of those unable towalk.[22] In those who are able to walk, DVT can reduceone's ability to do so.[23] The pain can be described asthrobbing and can worsen with weight-bearing, promptingone to bear more weight with the unaffected leg.[21][24]Additional signs and symptoms include tenderness, pittingedema (see image), dilation of surface veins, warmth,discoloration, a \"pulling sensation\", and even cyanosis (ablue or purplish discoloration) with fever.[5][20][21] DVT canalso exist without causing any symptoms.[22] Signs andsymptoms help in determining the likelihood of DVT, butthey are not used alone for diagnosis.[19]At times, DVT can cause symptoms in both arms or both legs, as with bilateral DVT.[25] Rarely, aclot in the inferior vena cava can cause both legs to swell.[26] Superficial vein thrombosis, alsoknown as superficial thrombophlebitis, is the formation of a blood clot (thrombus) in a vein closeto the skin. It can co-occur with DVT and can be felt as a \"palpable cord\".[20] Migratorythrombophlebitis (Trousseau's syndrome) is a noted finding in those with pancreatic cancer andis associated with DVT.[27]A pulmonary embolism (PE) occurs when a blood clot from a deep vein (a DVT) detaches from avein (embolizes), travels through the right side of the heart, and becomes lodged as an embolusin a pulmonary artery that supplies deoxygenated blood to the lungs for oxygenation.[28] Up toone-fourth of PE cases are thought to result in sudden death.[12] When not fatal, PE can causesymptoms such as sudden onset shortness of breath or chest pain, coughing up blood(hemoptysis), and fainting (syncope).[29][30] The chest pain can be pleuritic (worsened by deepbreaths)[29] and can vary based upon where the embolus is lodged in the lungs. An estimated30–50% of those with PE have detectable DVT by compression ultrasound.[30]A rare and massive DVT that causes significant obstruction and discoloration (includingcyanosis) is phlegmasia cerulea dolens.[31][32] It is life-threatening, limb-threatening, and carriesa risk of venous gangrene.[33] Phlegmasia cerulea dolens can occur in the arm but morecommonly affects the leg.[34][35] If found in the setting of acute compartment syndrome, anurgent fasciotomy is warranted to protect the limb.[36] Superior vena cava syndrome is a rarecomplication of arm DVT.[11]DVT is thought to be able to cause a stroke in the presence of a heart defect. This is called aparadoxical embolism because the clot abnormally travels from the pulmonary circuit to thesystemic circuit while inside the heart. The defect of a patent foramen ovale is thought to allowSigns and symptomsAcute complications

clots to travel through the interatrial septum from the right atrium into the left atrium.[37][38]A CT image with red arrows A case of phlegmasiaindicating PE (grey) in the cerulea dolens in thepulmonary arteries (white)left legA depiction of a patent foramenovaleIn most suspected cases, DVT is ruled out after evaluation.[39] Cellulitis is a frequent mimic ofDVT, with its triad of pain, swelling, and redness.[20] Symptoms concerning for DVT are moreoften due to other causes, including cellulitis, ruptured Baker's cyst, hematoma, lymphedema,and chronic venous insufficiency. Other differential diagnoses include tumors, venous or[1]arterial aneurysms, connective tissue disorders,[40] superficial vein thrombosis, muscle veinthrombosis, and varicose veins.[41]DVT and PE are the two manifestations of the cardiovascular disease venous thromboembolism(VTE).[2] VTE can occur as DVT only, DVT with PE, or PE only.[3] About two-thirds of VTEmanifests as DVT only, with one-third manifesting as PE with or without DVT.[12] VTE, alongwith superficial vein thrombosis, are common types of venous thrombosis.[10]Differential diagnosisClassification

The iliac veins (in the pelvis) include the externaliliac vein, the internal iliac vein, and the commoniliac vein. The common femoral vein is below theexternal iliac vein. (It is labeled simply \"femoral\"here.)Depiction of DVTDVT is classified as acute when the clots aredeveloping or have recently developed, whereaschronic DVT persists more than 28 days.[42]Differences between these two types of DVT canbe seen with ultrasound.[43] An episode of VTEafter an initial one is classified as recurrent.[44]Bilateral DVT refers to clots in both limbs whileunilateral means only a single limb isaffected.[45]DVT in the legs is proximal when above theknee and distal (or calf) when below theknee.[46] DVT below the popliteal vein, aproximal vein behind the knee, is classified asdistal[47] and has limited clinical significancecompared to proximal DVT.[48] Calf DVT makesup about half of DVTs.[49] Iliofemoral DVT hasbeen described as involving either the iliac orcommon femoral vein;[50] elsewhere, it hasbeen defined as involving at a minimum thecommon iliac vein, which is near the top of thepelvis.[19]DVT can be classified into provoked and unprovoked categories.[51] For example, DVT thatoccurs in association with cancer or surgery can be classified as provoked.[51] However, theEuropean Society of Cardiology in 2019 urged for this dichotomy to be abandoned to encouragemore personalized risk assessments for recurrent VTE.[52] The distinction between thesecategories is not always clear.[53]Traditionally, the three factors of Virchow's triad—venousstasis, hypercoagulability, and changes in the endothelialblood vessel lining—contribute to VTE and were used toexplain its formation.[54] More recently, inflammation hasbeen identified as playing a clear causal role.[13] Otherrelated causes include activation of immune systemcomponents, the state of microparticles in the blood, theconcentration of oxygen, and possible platelet activation.[55]Various risk factors contribute to VTE, including genetic andenvironmental factors, though many with multiple riskfactors never develop it.[56][57]Acquired risk factors include the strong risk factor of olderage,[5] which alters blood composition to favor clotting.[58]Previous VTE, particularly unprovoked VTE, is a strong riskfactor.[59] A leftover clot from a prior DVT increases the riskof a subsequent DVT.[60] Major surgery and trauma increaserisk because of tissue factor from outside the vascular systementering the blood.[61] Minor injuries,[62] lower limb amputation,[63] hip fracture, and long bonefractures are also risks.[9] In orthopedic surgery, venous stasis can be temporarily provoked by acessation of blood flow as part of the procedure.[55] Inactivity and immobilization contribute tovenous stasis, as with orthopedic casts,[64] paralysis, sitting, long-haul travel, bed rest,Causes

The coagulation system, often described as a \"cascade\",includes a group of proteins that regulate clotting. DVT riskcan be altered by abnormalities in the cascade. Theregulators, antithrombin (ᾳTHR) and activated protein C(APC), are shown in green above the clotting factors theyaffect.hospitalization,[61] and in survivors of acute stroke.[65] Conditions that involve compromisedblood flow in the veins are May–Thurner syndrome, where a vein of the pelvis is compressed,and venous thoracic outlet syndrome, which includes Paget–Schroetter syndrome, wherecompression occurs near the base of the neck.[66][67][68]Infections, including sepsis, COVID-19, HIV, and active tuberculosis, increaserisk.[69][70][71][72][73] Chronic inflammatory diseases and some autoimmune diseases,[74] such asinflammatory bowel disease,[75] systemic sclerosis,[76] Behçet's syndrome,[77] primaryantiphospholipid syndrome,[78] and systemic lupus erythematosus (SLE)[79] increase risk. SLEitself is frequently associated with secondary antiphospholipid syndrome.[80]Cancer can grow in and around veins, causing venous stasis, and can also stimulate increasedlevels of tissue factor.[81] Cancers of the blood, lung, pancreas, brain, stomach, and bowel areassociated with high VTE risk.[82] Solid tumors such as adenocarcinomas can contribute to bothVTE and disseminated intravascular coagulation. In severe cases, this can lead to simultaneousclotting and bleeding.[83] Chemotherapy treatment also increases risk.[84] Obesity increases thepotential of blood to clot, as does pregnancy. In the postpartum, placental tearing releasessubstances that favor clotting. Oral contraceptives[b] and hormonal replacement therapyincrease the risk through a variety of mechanisms, including altered blood coagulation proteinlevels and reduced fibrinolysis.[55]Dozens of genetic risk factors have beenidentified,[14] and they account forapproximately 50 to 60% of the variabilityin VTE rates.[4] As such, family history ofVTE is a risk factor for a first VTE.[86]Factor V Leiden, which makes factor Vresistant to inactivation by activatedprotein C,[86] mildly increases VTE risk byabout three times.[14][86] Deficiencies ofthree proteins that normally preventblood from clotting—protein C, protein S,and antithrombin—contribute to VTE.These deficiencies in antithrombin,protein C, and protein S are rare but[c]strong, or moderately strong, riskfactors.[61][55] They increase risk by about10 times.[87] Having a non-O blood typeroughly doubles VTE risk.[55] Non-Oblood type is common globally, making itan important risk factor.[88] Individualswithout O blood type have higher bloodlevels of von Willebrand factor and factorVIII than those with O blood type,increasing the likelihood of clotting.[88] Those homozygous for the common fibrinogen gammagene variant rs2066865 have about a 1.6 times higher risk of VTE.[89] The genetic variantprothrombin G20210A, which increases prothrombin levels,[61] increases risk by about 2.5times.[14] Additionally, approximately 5% of people have been identified with a backgroundgenetic risk comparable to the factor V Leiden and prothrombin G20210A mutations.[14]Blood alterations including dysfibrinogenemia,[64] low free protein S,[57] activated protein Cresistance,[57] homocystinuria,[90] hyperhomocysteinemia,[61] high fibrinogen levels,[61] highfactor IX levels,[61] and high factor XI levels[61] are associated with increased risk. Other

associated conditions include heparin-induced thrombocytopenia, catastrophic antiphospholipidsyndrome,[91] paroxysmal nocturnal hemoglobinuria,[92] nephrotic syndrome,[57] chronic kidneydisease,[93] polycythemia vera, essential thrombocythemia,[94] intravenous drug use,[95] andsmoking.[d]Some risk factors influence the location of DVT within the body. In isolated distal DVT, theprofile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery andimmobilization, appear to dominate, whereas thrombophilias and age do not seem to increase[e]risk.[99] Common risk factors for having an upper extremity DVT include having an existingforeign body (such as a central venous catheter, a pacemaker, or a triple-lumen PICC line),cancer, and recent surgery.[11]Blood has a natural tendency to clot when blood vessels are damaged (hemostasis) to minimizeblood loss.[100] Clotting is activated by the coagulation cascade and the clearing of clots that areno longer needed is accomplished by the process of fibrinolysis. Reductions in fibrinolysis orincreases in coagulation can increase the risk of DVT.[100]DVT often develops in the calf veins and \"grows\" in the direction of venous flow, towards theheart.[42][101] DVT most frequently affects veins in the leg or pelvis[9] including the popliteal vein(behind the knee), femoral vein (of the thigh), and iliac veins of the pelvis. Extensive lower-extremity DVT can even reach into the inferior vena cava (in the abdomen).[102] Upper extremityDVT most commonly affects the subclavian, axillary, and jugular veins.[11]Pathophysiology

Upper extremity DVTs can occur in the subclavian, axillary,brachial, ulnar, and radial veins (pictured) and the jugularand brachiocephalic veins (not pictured). The cephalic andbasilic veins, however, are superficial veins.[11]The process of fibrinolysis, where DVT clots can be dissolved back into the blood, acts to temperthe process of thrombus growth.[103] This is the preferred process. Aside from the potentiallydeadly process of embolization, a clot can resolve through organization, which can damage thevalves of veins, cause vein fibrosis, and result in non-compliant veins.[104][105] Organization of athrombus into the vein can occur at the third stage of its pathological development, in whichcollagen becomes the characteristic component. The first pathological stage is marked by redblood cells, and the second is characterized by medium-textured fibrin.[105]In arterial thrombosis, blood vessel walldamage is required, as it initiatescoagulation,[106] but clotting in the veinsmostly occurs without any suchmechanical damage.[61] The beginning ofvenous thrombosis is thought to arisefrom \"activation of endothelial cells,platelets, and leukocytes, with initiation ofinflammation and formation ofmicroparticles that trigger the coagulationsystem\" via tissue factor.[75] Vein wallinflammation is likely the incitingevent.[75] Importantly, the activatedendothelium of veins interacts withcirculating white blood cells(leukocytes).[54]While leukocytesnormally help prevent blood from clotting(as does normal endothelium), uponstimulation, leukocytes facilitateclotting.[107] Neutrophils are recruitedearly in the process of venous thrombiformation.[54] They release pro-coagulantgranules[107] and neutrophil extracellulartraps (NETs) or their components, whichplay a role in venous thrombiformation.[54][108] NET components arepro-thrombotic through both the intrinsicand extrinsic coagulation pathways.[108] NETs provide \"a scaffold for adhesion\" of platelets, redblood cells, and multiple factors that potentiate platelet activation.[109] In addition to the pro-coagulant activities of neutrophils, multiple stimuli cause monocytes to release tissue factor.[107]Monocytes are also recruited early in the process.[54]Tissue factor, via the tissue factor–factor VIIa complex,[110] activates the extrinsic pathway ofcoagulation and leads to conversion of prothrombin to thrombin, followed by fibrindeposition.[84] Fresh venous clots are red blood cell and fibrin rich.[42] Platelets and white bloodcells are also components. Platelets are not as prominent in venous clots as they are in arterialones, but they can play a role.[55] In cancer, tissue factor is produced by cancer cells.[111] Canceralso produces unique substances that stimulate factor Xa, cytokines that promote endothelialdysfunction, and plasminogen activator inhibitor-1, which inhibits the breakdown of clots(fibrinolysis).[111]Often, DVT begins in the valves of veins.[103] The blood flow pattern in the valves can cause lowoxygen concentrations in the blood (hypoxemia) of a valve sinus. Hypoxemia, which is worsenedby venous stasis, activates pathways—ones that include hypoxia-inducible factor-1 and early-growth-response protein 1. Hypoxemia also results in the production of reactive oxygen species,which can activate these pathways, as well as nuclear factor-κB, which regulates hypoxia-

D-dimer productioninducible factor-1 transcription.[84] Hypoxia-induciblefactor-1 and early-growth-response protein 1 contribute tomonocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filledmicrovesicles, which presumably begin clotting after bindingto the endothelial surface.[84]D-dimers are a fibrin degradation product, a naturalbyproduct of fibrinolysis that is typically found in the blood.An elevated level can result from plasmin dissolving a clot[f]—or other conditions.[112] Hospitalized patients often haveelevated levels for multiple reasons.[39] Anticoagulation, thestandard treatment for DVT, prevents further clot growth and PE, but does not act directly onexisting clots.[113]A clinical probability assessment using the Wells score (see dedicated column in the tablebelow) to determine if a potential DVT is \"likely\" or \"unlikely\" is typically the first step of thediagnostic process. The score is used in suspected first lower extremity DVT (without any PEsymptoms) in primary care and outpatient settings, including the emergency department.[1][5]The numerical result (possible score −2 to 9) is most commonly grouped into either \"unlikely\" or\"likely\" categories.[1][5] A Wells score of two or more means DVT is considered \"likely\" (about a28% chance), while those with a lower score are considered \"unlikely\" to have DVT (about a 6%chance).[39] In those unlikely to have DVT, a diagnosis is excluded by a negative D-dimer bloodtest. In people with likely DVT, ultrasound is the standard imaging used to confirm or exclude[1]a diagnosis.[5] Imaging is also needed for hospital inpatients with suspected DVT and thoseinitially categorized as unlikely to have DVT but who have a positive D-dimer test.[1]While the Wells score is the predominant and most studied clinical prediction rule forDVT,[39][114] it does have drawbacks. The Wells score requires a subjective assessment regardingthe likelihood of an alternate diagnosis and performs less well in the elderly and those with aprior DVT. The Dutch Primary Care Rule has also been validated for use. It contains onlyobjective criteria but requires obtaining a D-dimer value.[115] With this prediction rule, threepoints or less means a person is at low risk for DVT. A result of four or more points indicates anultrasound is needed.[115] Instead of using a prediction rule, experienced physicians can make aDVT pre-test probability assessment using clinical assessment and gestalt, but prediction rulesare more reliable.[1]Diagnosis

CriteriaWells scorefor DVT[g]Dutch PrimaryCare RuleActive cancer (treatment within last 6 months or palliative)+1 point+1 pointCalf swelling ≥ 3 cm compared to asymptomatic calf (measured 10 cmbelow tibial tuberosity)+1 point+2 pointsSwollen unilateral superficial veins (non-varicose, in symptomatic leg)+1 point+1 pointUnilateral pitting edema (in symptomatic leg)+1 point—Previous documented DVT+1 point—Swelling of entire leg+1 point—Localized tenderness along the deep venous system+1 point—Paralysis, paresis, or recent cast immobilization of lower extremities+1 point—Recently bedridden ≥ 3 days, or major surgery requiring regional orgeneral anesthetic in the past 12 weeks+1 point+1 pointAlternative diagnosis at least as likely−2 points—Positive D-dimer (≥ 0.5 mcg/mL or 1.7 nmol/L)—+6 pointsAbsence of leg trauma—+1 pointMale sex—+1 pointUse of oral contraceptives—+1 point[5][115]Compression ultrasonography for suspected deep vein thrombosis is the standard diagnosticmethod, and it is highly sensitive for detecting an initial DVT.[117] A compression ultrasound isconsidered positive when the vein walls of normally compressible veins do not collapse undergentle pressure.[39] Clot visualization is sometimes possible, but is not required.[118] Threecompression ultrasound scanning techniques can be used, with two of the three methodsrequiring a second ultrasound some days later to rule out the diagnosis.[117] Whole-legultrasound is the option that does not require a repeat ultrasound,[117] but proximal compressionultrasound is frequently used because distal DVT is only rarely clinically significant.[116]Ultrasound methods including duplex and color flow Doppler can be used to further characterizethe clot[116] and Doppler ultrasound is especially helpful in the non-compressible iliac veins.[118]CT scan venography, MRI venography, or a non-contrast MRI are also diagnosticpossibilities.[119] The gold standard for judging imaging methods is contrast venography, whichinvolves injecting a peripheral vein of the affected limb with a contrast agent and taking X-rays,to reveal whether the venous supply has been obstructed. Because of its cost, invasiveness,availability, and other limitations, this test is rarely performed.[39]

An ultrasound with a blood clot Doppler ultrasonography showing absence of flow andvisible in the left common femoral hyperechogenic content in a clotted femoral veinvein. (The common femoral vein (labeled subsartorial ) distal to the branching point ofis distal to the external iliac vein.) the deep femoral vein. When compared to this clot,[h]clots that instead obstruct the common femoral vein(proximal to this branching point) cause more severeeffects due to impacting a significantly larger portion ofthe leg.[121]An abdominal CT scan demonstrating an iliofemoral DVT,with the clot in the right common iliac vein of the pelvisTreatment for DVT is warranted when the clots are either proximal, distal and symptomatic, orupper extremity and symptomatic.[2] Providing anticoagulation, or blood-thinning medicine, isthe typical treatment after patients are checked to make sure they are not subject tobleeding.[2][i] However, treatment varies depending upon the location of DVT. For example, incases of isolated distal DVT, ultrasound surveillance (a second ultrasound after 2 weeks to checkfor proximal clots), might be used instead of anticoagulation.[5][123] Although, those withisolated distal DVT at a high-risk of VTE recurrence are typically anticoagulated as if they hadManagement

Structural representations of the backbone of heparins (left), which vary in the size of their chain, and thesynthetic pentasaccaride (five-sugar) fondaparinux (right)proximal DVT. Those at a low-risk for recurrence might receive a four to six week course ofanticoagulation, lower doses, or no anticoagulation at all.[5] In contrast, those with proximalDVT should receive at least 3 months of anticoagulation.[5]Some anticoagulants can be taken by mouth, and these oral medicines include warfarin (avitamin K antagonist), rivaroxaban (a factor Xa inhibitor), apixaban (a factor Xa inhibitor),dabigatran (a direct thrombin inhibitor), and edoxaban (a factor Xa inhibitor).[2] Otheranticoagulants cannot be taken by mouth. These parenteral (non-oral) medicines include low-molecular-weight heparin, fondaparinux, and unfractionated heparin. Some oral medicines aresufficient when taken alone, while others require the use of an additional parenteral bloodthinner. Rivaroxaban and apixaban are the typical first-line medicines, and they are sufficientwhen taken orally.[19] Rivaroxaban is taken once daily, and apixaban is taken twice daily.[5]Warfarin, dabigatran, and edoxaban require the use of a parenteral anticoagulant to initiate oralanticoagulant therapy.[19][124] When warfarin is initiated for VTE treatment, a 5-day minimum ofa parenteral anticoagulant together with warfarin is given, which is followed by warfarin-only[j]therapy.[17][18] Warfarin is taken to maintain an international normalized ratio (INR)[k] of 2.0–3.0, with 2.5 as the target.[127] The benefit of taking warfarin declines as the duration oftreatment extends,[128] and the risk of bleeding increases with age.[129] Periodic INR monitoringis not necessary when first-line direct oral anticoagulants are used. Overall, anticoagulationtherapy is complex and many circumstances can affect how these therapies are managed.[130]The duration of anticoagulation therapy (whether it will last 4 to 6 weeks,[5] 6 to 12 weeks, 3 to 6months,[19] or indefinitely) is a key factor in clinical decision making.[51] When proximal DVT isprovoked by surgery or trauma a 3-month course of anticoagulation is standard.[19] When a firstVTE is proximal DVT that is either unprovoked or associated with transient non-surgical riskfactor, low-dose anticoagulation beyond 3 to 6 months might be used.[19] In those with an annualrisk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is apossibility.[131] Those who finish warfarin treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results),and this result might be used in clinical decision making.[132] Thrombophilia test results rarelyplay a role in the length of treatment.[78]Treatment for acute leg DVT is suggested to continue at home for uncomplicated DVT instead ofhospitalization. Factors that favor hospitalization include severe symptoms or additional medicalissues.[12] Early walking is suggested over bedrest.[133] Graduated compression stockings—whichapply higher pressure at the ankles and a lower pressure around the knees[125] can be trialed forsymptomatic management of acute DVT symptoms, but they are not recommended for reducingthe risk of post-thrombotic syndrome,[124] as the potential benefit of using them for this goal\"may be uncertain\".[5] Nor are compression stockings likely to reduce VTE recurrence.[134] Theyare, however, recommended in those with isolated distal DVT.[5]

If someone decides to stop anticoagulation after an unprovoked VTE instead of being on lifelonganticoagulation, aspirin can be used to reduce the risk of recurrence,[135] but it is only about 33%as effective as anticoagulation in preventing recurrent VTE.[51] Statins have also beeninvestigated for their potential to reduce recurrent VTE rates, with some studies suggestingeffectiveness.[136]An unprovoked VTE might signal the presence of an unknown cancer, as it is an underlyingcondition in up to 10% of unprovoked cases. A thorough clinical assessment is needed and[1]should include a physical examination, a review of medical history, and universal cancerscreening done in people of that age.[19][137] A review of prior imaging is considered worthwhile,as is \"reviewing baseline blood test results including full blood count, renal and hepatic function,PT and APTT.\"[137] It is not recommended practice to obtain tumor markers or a CT of theabdomen and pelvis in asymptomatic individuals. NICE recommends that further[1]investigations are unwarranted in those without relevant signs or symptoms.[137]Thrombolysis is the injection of an enzyme into the veins to dissolve blood clots, and while thistreatment has been proven effective against the life-threatening emergency clots of stroke andheart attacks, randomized controlled trials[138][139][140] have not established a net benefit inthose with acute proximal DVT.[5][141] Drawbacks of catheter-directed thrombolysis (thepreferred method of administering the clot-busting enzyme[5]) include a risk of bleeding,complexity, and the cost of the procedure.[l][124] Although, while anticoagulation is the preferredtreatment for DVT,[124] thrombolysis is a treatment option for those with the severe DVT form ofphlegmasia cerula dorens (bottom left image) and in some younger patients with DVT affectingthe iliac and common femoral veins.[12] Of note, a variety of contraindications to thrombolysisexist.[124] In 2020, NICE kept their 2012 recommendations that catheter-directed thrombolysisshould be considered in those with iliofemoral DVT who have \"symptoms lasting less than 14days, good functional status, a life expectancy of 1 year or more, and a low risk of bleeding.\"[137]A mechanical thrombectomy device can remove DVT clots, particularly in acute iliofemoral DVT(DVT of the major veins in the pelvis), but there is limited data on its efficacy. It is usuallycombined with thrombolysis, and sometimes temporary IVC filters are placed to protect againstPE during the procedure.[142] Catheter-directed thrombolysis with thrombectomy[140] againstiliofemoral DVT has been associated with a reduction in the severity of post-thromboticsyndrome at an estimated cost-effectiveness ratio of about $138,000[m] per gainedQALY.[143][144] Phlegmasia cerulea dolens might be treated with catheter-directed thrombolysisand/or thrombectomy.[19][142]In DVT in the arm, the first (topmost) rib can be surgically removed as part of the typicaltreatment when the DVT is due to thoracic outlet syndrome or Paget–Schroetter syndrome. Thistreatment involves initial anticoagulation followed by thrombolysis of the subclavian vein andstaged first rib resection to relieve the thoracic outlet compression and prevent recurrentDVT.[145]Investigations for cancerInterventions

The first rib, which is A venogram before catheter-directedremoved in a first rib thrombolysis resection surgery, is syndrome, a rare and severe arm DVTlabeled 1 in this image shown here in a judo practitioner, withfor Paget–Schroetterhighly restricted blood flow shown inthe veinAfter treatment with catheter-directed thrombolysis, blood flowin the axillary and subclavian veinwere significantly improved.Afterwards, a first rib resectionallowed decompression. Thisreduces the risk of recurrent DVTand other sequelae from thoracicoutlet compression.[146]The placement of an inferior vena cava filter (IVC filter) is possible when either the standardtreatment for acute DVT, anticoagulation, is absolutely contraindicated (not possible), or ifsomeone develops a PE despite being anticoagulated.[137] However, a 2020 NICE review found\"little good evidence\" for their use.[137] A 2018 study associated IVC filter placement with a 50%reduction in PE, a 70% increase in DVT, and an 18% increase in 30 day mortality whencompared to no IVC placement.[1][147] Other studies including a systematic review and meta-analysis did not find a difference in mortality with IVC placement.[30] If someone develops a PE

An IVC filterdespite being anticoagulated, care should be given tooptimize anticoagulation treatment and address otherrelated concerns before considering IVC filterplacement.[137]Patients with a history of DVT might be managed by primarycare, general internal medicine, hematology, cardiology,vascular surgery, or vascular medicine.[148] Patientssuspected of having an acute DVT are often referred to the emergency department forevaluation.[149] Interventional radiology is the specialty that typically places and retrieves IVCfilters,[150] and vascular surgery might do catheter directed thrombosis for some severeDVTs.[146]For the prevention of blood clots in the general population, incorporating leg exercises whilesitting down for long periods, or having breaks from a sitting position and walking around,having an active lifestyle, and maintaining a healthy body weight are recommended.[6] Walkingincreases blood flow through the leg veins.[151] Excess body weight is modifiable unlike most riskfactors, and interventions or lifestyle modifications that help someone who is overweight orobese lose weight reduce DVT risk.[86] Avoiding both smoking and a Western pattern diet arethought to reduce risk.[152] Statins have been investigated for primary prevention (prevention ofa first VTE), and the JUPITER trial, which used rosuvastatin, has provided some tentativeevidence of effectiveness.[14][153] Of the statins, rosuvastatin appears to be the only one with thepotential to reduce VTE risk.[154] If so, it appears to reduce risk by about 15%.[152] However, thenumber needed to treat to prevent one initial VTE is about 2000, limiting its applicability.[155]Acutely ill hospitalized patients are suggested to receive a parenteral anticoagulant, although thepotential net benefit is uncertain.[62] Critically ill hospitalized patients are recommended toeither receive unfractionated heparin or low-molecular weight heparin instead of foregoing thesemedicines.[62]Major orthopedic surgery—total hip replacement, total knee replacement, or hip fracture surgery—has a high risk of causing VTE.[156] If prophylaxis is not used after these surgeries,symptomatic VTE has about a 4% chance of developing within 35 days.[157] Following majororthopedic surgery, a blood thinner or aspirin is typically paired with intermittent pneumaticcompression, which is the preferred mechanical prophylaxis over graduated compressionstockings.[7]Options for VTE prevention in people following non-orthopedic surgery include early walking,mechanical prophylaxis, and blood thinners (low-molecular-weight heparin and low-dose-unfractionated heparin) depending upon the risk of VTE, risk of major bleeding, and person'spreferences.[158] After low-risk surgeries, early and frequent walking is the best preventivemeasure.[7]Field of medicinePreventionHospital (non-surgical) patientsAfter surgery

The incision for a completed kneereplacement surgery, a procedurethat can precipitate DVT formationAn example of a compressionstockingThe risk of VTE is increased in pregnancy by about four tofive times because of a more hypercoagulable state thatprotects against fatal postpartum hemorrhage.[28]Preventive measures for pregnancy-related VTE weresuggested by the American Society of Hematology in2018.[159] Warfarin, a common vitamin K antagonist, cancause birth defects and is not used for prevention duringpregnancy.[160]Travelling \"is an oftencited yet relativelyuncommon\" cause ofVTE.[28] Suggestions forat-risk[n]long-haultravelers include calfexercises, frequentwalking, and aisle seating in airplanes to easewalking.[161][162] Graduated compression stockings havesharply reduced the levels of asymptomatic DVT in airlinepassengers, but the effect on symptomatic DVT, PE, ormortality is unknown, as none of the individuals studieddeveloped these outcomes.[163]However, graduatedcompression stockings are not suggested for long-haultravelers (>4 hours) without risk factors for VTE. Likewise,neither aspirin nor anticoagulants are suggested in thegeneral population undertaking long-haul travel.[62] Thosewith significant VTE risk factors[o] undertaking long-haultravel are suggested to use either graduated compressionstockings or LMWH for VTE prevention. If neither of thesetwo methods are feasible, then aspirin is suggested.[62]DVT is most frequently a disease of older age that occurs in the context of nursing homes,hospitals, and active cancer.[3] It is associated with a 30-day mortality rate of about 6%, with PEbeing the cause of most of these deaths. Proximal DVT is frequently associated with PE, unlike[1]distal DVT, which is rarely if ever associated with PE.[39] Around 56% of those with proximalDVT also have PE, although a chest CT is not needed simply because of the presence of DVT. If[1]proximal DVT is left untreated, in the following 3 months approximately half of people willexperience symptomatic PE.[9]Another frequent complication of proximal DVT, and the most frequent chronic complication, ispost-thrombotic syndrome, where individuals have chronic venous symptoms.[5] Symptoms caninclude pain, itching, swelling, paresthesia, a sensation of heaviness, and in severe cases, legulcers.[5] After proximal DVT, an estimated 20–50% of people develop the syndrome, with 5–10% experiencing severe symptoms.[164] Post-thrombotic syndrome can also be a complication ofdistal DVT, though to a lesser extent than with proximal DVT.[165]PregnancyTravelersPrognosis

In the 10 years following an initial VTE, about 30% of people will have a recurrence.[3] VTErecurrence in those with prior DVT is more likely to recur as DVT than PE.[166] Cancer[5] andunprovoked DVT are strong risk factors for recurrence.[59] After initial proximal unprovokedDVT with and without PE, 16–17% of people will have recurrent VTE in the 2 years after theycomplete their course of anticoagulants. VTE recurrence is less common in distal DVT thanproximal DVT.[44] In upper extremity DVT, annual VTE recurrence is about 2–4%.[129] Aftersurgery, a provoked proximal DVT or PE has an annual recurrence rate of only 0.7%.[59]About 1.5 out of 1000 adults a year have a first VTE in high-income countries.[167][168] Thecondition becomes much more common with age.[3] VTE rarely occurs in children, but when itdoes, it predominantly affects hospitalized children.[169] Children in North America and theNetherlands have VTE rates that range from 0.07 to 0.49 out of 10,000 children annually.[169]Meanwhile, almost 1% of those aged 85 and above experience VTE each year.[3] About 60% of allVTEs occur in those 70 years of age or older.[9] Incidence is about 18% higher in males than infemales,[4] though there are ages when VTE is more prevalent in women.[15] VTE occurs inassociation with hospitalization or nursing home residence about 60% of the time, active cancerabout 20% of the time, and a central venous catheter or transvenous pacemaker about 9% of thetime.[3]During pregnancy and after childbirth, acute VTE occurs in about 1.2 of 1000 deliveries. Despiteit being relatively rare, it is a leading cause of maternal morbidity and mortality.[159] Aftersurgery with preventive treatment, VTE develops in about 10 of 1000 people after total or partialknee replacement, and in about 5 of 1000 after total or partial hip replacement.[170] About400,000 Americans develop an initial VTE each year, with 100,000 deaths or more attributableto PE.[168] Asian, Asian-American, Native American, and Hispanic individuals have a lower VTErisk than Whites or Blacks.[4][15] Populations in Asia have VTE rates at 15 to 20% of what is seenin Western countries, with an increase in incidence seen over time.[16] In North American andEuropean populations, around 4–8% of people have a thrombophilia,[87] most commonly factorV leiden and prothrombin G20210A. For populations in China, Japan, and Thailand, deficiencesin protein S, protein C, and antithrombin predominate.[171] Non-O blood type is present inaround 50% of the general population and varies with ethnicity, and it is present in about 70% ofthose with VTE.[88][172]DVT occurs in the upper extremities in about 4–10% of cases,[11] with an incidence of 0.4–1.0people out of 10,000 a year.[5] A minority of upper extremity DVTs are due to Paget–Schroettersyndrome, also called effort thrombosis, which occurs in 1–2 people out of 100,000 a year,usually in athletic males around 30 years of age or in those who do significant amounts ofoverhead manual labor.[67][146]Being on blood thinners because of DVT can be life-changing because it can prevent lifestyleactivities such as contact or winter sports to prevent bleeding after potential injuries.[174] Headinjuries prompting brain bleeds are of particular concern. This has caused NASCAR driver BrianVickers to forego participation in races. Professional basketball players including NBA playersChris Bosh and hall of famer Hakeem Olajuwon have dealt with recurrent blood clots,[175] andBosh's career was significantly hampered by DVT and PE.[176]EpidemiologySocial

Serena Williams has spoken at lengthabout a frightening encounter she had withVTE while she was hospitalized in2017.[173]Rudolf VirchowTennis star Serena Williams was hospitalized in 2011for PE thought to have originated from DVT.[177] Yearslater, in 2017, due to her knowledge of DVT and PE,Serena accurately advocated for herself to have a PEdiagnosed and treated. During this encounter withVTE, she was hospitalized after a C-section surgery andwas off of blood thinners. After feeling the suddenonset of a PE symptom, shortness of breath, she toldher nurse and requested a CT scan and an IV heparindrip, all while gasping for air. She started to receive anultrasound to look for DVT in the legs, prompting herto express dissatisfaction to the medical staff that theywere not looking for clots where she had symptoms(her lungs), and they were not yet treating herpresumed PE. After being diagnosed with PE and notDVT, and after receiving heparin by IV, the coughingfrom the PE caused her C-section surgical site to openand the heparin contributed to bleeding at the site.Serena later received an IVC filter while in thehospital.[173][178]Other notable people have been affected by DVT.Former United States (US) President Richard Nixonhad recurrent DVT,[179] and so has former Secretary ofState Hillary Clinton. She was first diagnosed whileFirst Lady in 1998 and again in 2009.[180] Dick Cheney was diagnosed with an episode whileVice President,[181] and TV show host Regis Philbin had DVT after hip-replacement surgery.[182]DVT has also contributed to the deaths of famous people. For example, DVT and PE played a rolein rapper Heavy D's death at age 44.[183] NBC journalist David Bloom died at age 39 whilecovering the Iraq War from a PE that was thought to have progressed from a missed DVT,[184]and actor Jimmy Stewart had DVT that progressed to a PE when he was 89.[182][185]The book Sushruta Samhita, an Ayurvedic text publishedaround 600–900 BC, contains what has been cited as thefirst description of DVT.[186] In 1271, DVT symptoms in theleg of a 20-year-old male were described in a Frenchmanuscript, which has been cited as the first case or the firstWestern reference to DVT.[186][187]In 1856, German physician and pathologist Rudolf Virchowpublished his analysis after the insertion of foreign bodiesinto the jugular veins of dogs, which migrated to thepulmonary arteries. These foreign bodies caused pulmonaryemboli, and Virchow was focused on explaining theirconsequences.[188] He cited three factors, which are nowunderstood as hypercoaguability, stasis, and endothelialinjury.[189] It was not until 1950 that this framework wascited as Virchow's triad,[188] but the teaching of Virchow'striad has continued in light of its utility as a theoreticalframework and as a recognition of the significant progress Virchow made in expanding theunderstanding of VTE.[188][189]History

Warfarin, a common vitamin Kantagonist, was the mainstay ofpharmacological treatment for about50 years.Methods to observe DVT by ultrasound were established in the 1960s.[119] Diagnoses werecommonly performed by impedance plethysmography in the 1970s and 1980s,[190] butultrasound, particularly after utility of probe compression was demonstrated in 1986, became thepreferred diagnostic method.[186] Yet, in the mid 1990s, contrast venography and impedanceplethysmography were still described as common.[191]Multiple pharmacological therapies for DVT were introducedin the 20th century: oral anticoagulants in the 1940s,subcutaneous injections of LDUH in 1962 and subcutaneousinjections of LMWH in 1982.[192] 1974 was when vascularinflammation and venous thrombosis were first proposed tobe interrelated.[110] For around 50 years, a months-longwarfarin (Coumadin) regimen was the mainstay ofpharmacological treatment.[193][194] To avoid the bloodmonitoring required with warfarin and the injectionsrequired by heparin and heparin-like medicines, direct oralanticoagulants (DOACs) were developed.[194] In the late2000s to early 2010s, DOACs—including rivaroxaban(Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa)—came to the market.[59]The New York Times described a\"furious battle\" among the three makers of these drugs \"for the prescription pads of doctors\".[193]VTE costs the US healthcare system about $7 to 10 billion dollars annually.[168] Initial andaverage DVT costs for a hospitalized US patient is about $10,000 (2015 estimate).[195] In Europe,the costs for an initial VTE hospitalization are significantly less, costing about €2000 to 4000(2011 estimate).[196] Post-thrombotic syndrome is a significant contributor to DVT follow-upcosts.[197] Outpatient treatment significantly reduces costs, and treatment costs for PE exceedthose of DVT.[198]A 2019 study published in Nature Genetics reported more than doubling the known genetic lociassociated with VTE.[14] In their updated 2018 clinical practice guidelines, the American Societyof Hematology identified 29 separate research priorities, most of which related to patients whoare acutely or critically ill.[62] Inhibition of factor XI, P-selectin, E-selectin, and a reduction information of neutrophil extracellular traps are potential therapies that might treat VTE withoutincreasing bleeding risk.[199]a. Venous thrombosis associated with drainage from the brain (cerebral venous sinusthrombosis), eyes (retinal vein thrombosis), spleen and intestines (splanchnic veinthrombosis), liver (Budd–Chiari syndrome), kidneys (renal vein thrombosis), and ovaries(ovarian vein thrombosis) are more unusual forms of venous thrombosis and they areconsidered as separate diseases.[10]b. Third-generation combined oral contraceptives (COCs) have an approximate two to threetimes higher risk than second-generation COCs.[63]Progestogen-only pill use is notassociated with increased VTE risk.[85]c. Type I[57]EconomicsResearch directionsNotes

d. \"It is important to note that smoking is not an independent risk factor, although it increasesthe risk for cancers and other comorbidities and works synergistically with other independentrisk factors.\"[96]e. The term 'thrombophilia' as used here applies to the five inherited abnormalities ofantithrombin, protein C, protein S, factor V, and prothrombin, as is done elsewhere.[87][97]These 5 genetic factors have been referred to as the classical thrombophilias.[98]f. An elevated level is greater than 250 ng/mL D-dimer units (DDU) or greater than 0.5 μg/mLfibrinogen equivalent units (FEU). A normal level is below these values.[112]g. The Wells score as displayed here is the more recent modified score, which added a criterionfor a previous documented DVT and increased the time range after surgery to 12 weeks from4 weeks.[116]h. Subsartorial is a proposed name for a section of the femoral vein.[120]i. Evidence for anticoagulation comes from studies other than definitive randomized controlledtrials that demonstrate efficacy and safety for anticoagulation vs. placebo or usingNSAIDs.[122]j. The international normalized ratio should be ≥ 2.0 for 24 hours minimum,[18] but if the ratio is> 3.0, then the parenteral anticoagulant is not needed for five days.[125]k. An INR is determined from the ratio of a patient's prothrombin time (PT) to a standardizedcontrol PT. A normal INR for those not on anticoagulation is 1.0. A value of 5.0 or higher isconsidered a critical finding because of an increased risk of bleeding.[126]l. \"Up to 83% of patients treated by any catheter-based therapy, need adjunctive angioplasty,and stenting\".[5]m. Estimated in United States dollars, estimate published in 2019n. Including those with \"previous VTE, recent surgery or trauma, active malignancy, pregnancy,estrogen use, advanced age, limited mobility, severe obesity, or known thrombophilicdisorder\"[161]o. For example \"recent surgery, history of VTE, postpartum women, active malignancy, or ≥2risk factors, including combinations of the above with hormone replacement therapy, obesity,or pregnancy\"[62]1. Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ (June 2019). \"Deep vein thrombosis:update on diagnosis and management\". The Medical Journal of Australia. 210 (11): 516–24.doi 10.5694/mja2.50201 (https://doi.org/10.5694%2Fmja2.50201) PMID 31155730 (https://p:. ubmed.ncbi.nlm.nih.gov/31155730) S2CID 173995098 (https://api.semanticscholar.org/Corp. usID:173995098).2. Bartholomew JR (December 2017). \"Update on the management of venousthromboembolism\" (https://www.ccjm.org/content/84/12_suppl_3/39). Cleveland ClinicJournal of Medicine. 84 (12 Suppl 3): 39–46. doi 10.3949/ccjm.84.s3.04 (https://doi.org/10.39:49%2Fccjm.84.s3.04) PMID 29257737 (https://pubmed.ncbi.nlm.nih.gov/29257737). .S2CID 3707226 (https://api.semanticscholar.org/CorpusID:3707226).3. Heit JA, Spencer FA, White RH (January 2016). \"The epidemiology of venousthromboembolism\" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715842). Journal ofThrombosis and Thrombolysis. 41 (1): 3–14. doi 10.1007/s11239-015-1311-6 (https://doi.org/:10.1007%2Fs11239-015-1311-6) PMC 4715842 (https://www.ncbi.nlm.nih.gov/pmc/articles/. PMC4715842) PMID 26780736 (https://pubmed.ncbi.nlm.nih.gov/26780736). .References

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