Bloody Easy 5

["B Administration & Infusion Practices Erythropoietin and Medical Patients Dosage !A T T E N T I O N n\tC\u0007aution: Administering 25% albumin Administering 25% albumin in error, instead of 5%, could result instead of 5% in error could in severe circulatory overload. result in circulatory overload! n\t\u0007For dosage, see specific indications listed below. n\t\u0007Intravascular volume response: 500 mL 5% albumin 100 mL 25% albumin* = 25 grams of albumin = 25 grams of albumin Fractionated Blood Products 500 mL increase 450 mL increase in in intravascular intravascular volume volume (350 mL from interstitial pool) *25% albumin usually restricted to use in patients with cirrhosis Administration 245,246 Sickle Cell Disease n\t\u0007No blood bank sample required. n\t\u0007Use vented IV tubing, no filter required. n\t\u0007Fluid compatibility: all IV solutions. n\t\u0007Record lot number and volume of albumin administered in patient chart. n\t\u0007The infusion rate of 5% albumin should not exceed 5ml\/min and the infusion rate for 25% albumin should not exceed 2ml\/min. Adverse reactions \/ Risks n\t\u0007Anaphylaxis \u2013 rare. n\t\u0007Circulatory overload.247 n\t\u0007Hypotension \u2013 rare case reports of transient hypotension in patients on angiotensin- converting enzyme inhibitors.248 n\t\u0007There are no reports of HIV, HCV, or other viruses transmitted through albumin. 101","FRACTIONATED BLOOD PRODUCTS : A l b u m i n C Indications ALBUMIN MAY BENEFIT THE FOLLOWING GROUPS OF PATIENTS: 1. Paracentesis n\t\u0007Albumin has been shown to reduce paracentesis induced circulatory dysfunction in the management of tense ascites by paracentesis.249 n\t\u0007For paracentesis of <5 litres \u2013 albumin is unnecessary.250 n\t\u0007For large volume paracentesis, albumin should be considered as the replacement fluid of choice. Volume of ascites 25% albumin* <5 L 0 5-6 litres 100 mL 6-8 litres 200 mL >8 litres drained 300 mL * 6-8 grams of albumin per L of fluid removed for paracentesis >5 L n\t\u0007There is preliminary evidence that !A T T E N T I O N midodrine251 and terlipressin252 may be alternative therapies to intravenous There is no evidence to albumin in this setting, but have not been support the use of albumin shown to be superior to albumin.253 in patients with malignant n\t\u0007\u0007Malignant ascites \u2013 there is no evidence ascites post-paracentesis. to support the use of albumin in patients with malignant ascites post-paracentesis.254 2. Spontaneous bacterial peritonitis n\t\u0007One RCT (n=126) found that patients resuscitated with antibiotics alone compared to antibiotics plus albumin had a higher mortality (OR 4.5, 95% CI 1.0 to 20.9).255 \t u \u0007This study has been criticized for lack of a formalized resuscitation protocol in the control arm. 102","DOSAGE Erythropoietin and Medical Patients n\t\u00072\u0007 5% albumin \u2013 1.5 g per kg within 6 hours of diagnosis and 1.0 g per kg on day 3. Fractionated Blood Products \t u U\u0007 se dry-weight of patient for dosing. \t u C\u0007 onsider dose reduction or administering over 3 days if patient at risk for transfusion-associated circulatory overload. \t u F\u0007 or example: for a 70 kg patient = 4 x 100 mL of 25% albumin on day 1 and then 3 x 100 mL of 25% albumin on day 3. 3. Hepatorenal syndrome !A T T E N T I O N Sickle Cell Disease n\t\u0007Preliminary data suggests that albumin Use of Intravenous albumin alone is in conjunction with terlipressin256 or ineffective for midodrine\/octreotide257 may be effective hepatorenal syndrome. for type 1 hepatorenal syndrome. There is evidence that the combination of terlipressin and albumin has a greater beneficial effect on renal failure than the combination of either midodrine or octreotide with albumin.258 \t u T\u0007 his therapy has not been shown to change mortality rates in hepato-renal syndrome. \t u A\u0007 lbumin alone, without terlipressin or other agent is ineffective.259 DOSAGE n\t\u00071\u0007 g\/kg of 25% albumin on day 1 to a maximum of 100 g (400 mL of 25%) and then 25 g (100 mL) daily thereafter for a maximum of 14 days.256 4. Plasma exchange n\t\u0007Currently, the majority of patients undergoing therapeutic plasma exchange are replaced with albumin \u00b1 crystalloid with the exception of patients with thrombotic thrombocytopenic purpura (TTP) who are replaced with frozen plasma. 103","FRACTIONATED BLOOD PRODUCTS : A l b u m i n THE CURRENT MEDICAL LITERATURE CANNOT CONFIRM ANY BENEFIT OF INTRAVENOUS ALBUMIN IN THE FOLLOWING SUBGROUPS OF PATIENTS: 1. Resuscitation n\t\u0007Current evidence: albumin is not superior to crystalloid for resuscitation in intensive care. n\t\u0007A systematic review from 2019 identified 55 randomized controlled trials comparing crystalloid with various colloids in intensive care patients. Data on mortality were available for 26,329 patients from 46 studies. There was no mortality benefit found when albumin was compared with crystalloid (Relative Risk (RR) 1.02 (95% CI 0.96-1.10)).260 n\t\u0007A systematic review published in 2014 included 16 randomized trials totaling 4,190 patients with sepsis who received crystalloid or intravenous albumin and found no difference in all-cause mortality (RR 0.94, 95% CI 0.87-1.01).261 2. Hypoalbuminemia n\t\u0007\u0007Current evidence: albumin is NOT superior to crystalloid for treatment of hypoalbuminemia. n\t\u0007A\u0007 n RCT (n=777) evaluated the role of albumin as compared to no albumin in hospitalized patients with decompensated cirrhosis and hypoalbuminemia (albumin <30 g\/L); there was no difference in the primary endpoint (composite of new infections, kidney dysfunction, or death between days 3 and 15) between groups (OR 0.98, 95%CI 0.71-1.33) and more severe or life-threatening serious adverse events were reported in the albumin treated patients.247 n\t\u0007O\u0007 ne meta-analysis showed a significant increase in mortality and another showed a non-significant increase in mortality compared to crystalloid: Cochrane Injuries Odds Ratio (OR)* OR Range % increase in mortality Group 262 1.69 1.07-2.67 69% (7 to 167%) 1.59 0.91-2.78 59% (-9 to 178%) Wilkes et al 263 104","3. Severe burns Erythropoietin and Medical Patients n\t\u0007A systematic review of randomized trials failed to show an improvement in mortality with intravenous albumin (Odds Ratio 1.41 (95% CI 0.27-7.38)).264 n\t\u0007There is currently a wide variation in fluid resuscitation practice in burn patients.265 n\t\u0007Current expert opinion recommends PARKLAND FORMULA Fractionated resuscitation with lactated Ringer\u2019s solution Blood Products according to the Parkland formula, with Parkland Formula = addition of colloids if the fluid volume 4 mL\/kg\/% burn over the exceeds 4 mL\/kg\/% burn (known as first 24 hours, with half of \u2018fluid creep\u2019) and urine output is less than the total fluid given in the 0.5 mL\/kg\/hour, with hemostatic instability first 8 hours to target urine after the first 8-24 hours.266,267 output to 0.5-1.0 mL\/kg\/hr. n\t\u0007Intravenous albumin should only be !A T T E N T I O N commenced after transfer to a specialized burn centre. Intravenous albumin should only be commenced after 4. Hypotension during dialysis transfer to a specialized n\t\u0007T\u0007 here are currently insufficient data to burn centre. support the routine use of albumin in the treatment of hypotension during dialysis. \t u \u0007There are 4 small trials comparing albumin Sickle Cell Disease to alternative fluids with uncertain benefits found in patients with intradialytic hypotension.268,269,270,271 5. Cardiac surgery272 105 n\t\u0007\u0007T\u0007 here is no evidence to support the use of albumin, as compared to starch or crystalloid, for either: \t\u0007i. \u0007Priming fluid for cardiopulmonary bypass \t ii. Post-cardiopulmonary bypass 6. Acute Lung Injury n\t\u0007A\u0007 systematic review from 2014 evaluated the impact of intravenous albumin, as compared to crystalloid, in patients with acute respiratory distress syndrome. Three small randomized trials totaling 204 patients were included; no difference in mortality was found (RR 0.89, 95% CI 0.62-1.28).273 n\t\u0007A\u0007 large RCT (1386) in patients undergoing cardiac surgery with albumin, as compared to Ringer\u2019s lactate solution, did not find a reduction in adverse outcomes. \t u P\u0007 atients randomized to albumin had higher rates of bleeding, re-sternotomy, and infections.274","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) A Basics IVIG is the fraction extracted from donated plasma that contains the immunoglobulins, with >90% as IgG. Products Available !A T T E N T I O N n\t\u0007Products are supplied by CBS or HQ. n\t\u0007Informed consent is required as for IVIG is a blood product. Consent required. any blood component or product. \t\u0007Refer to product\u2019s package insert for further details. IG PRODUCTS LICENSED IN CANADA* Product\t IGIVnex\t Gamunex\t Privigen\t Gammagard\tGammagard\t Hizentra\t Octagam\t Panzyga\tCuvitru\tCutaquig \t\t\t\tLiquid\t S\/D % 10% 10% 10% 10% 5\u201310% 20% 10% 10% 20% 16.5% Manufacturer Grifols Grifols CSL Behring Takeda Takeda CSL Behring Octapharma Octapharma Takeda Octapharma Plasma Canada United Canada\/ United United United United United United United Source States United States States States States States States States States >90 200 IgG (g\/L) 98 \u00b1 20 100 \u00b1 10 100 100 \u22642.2 mcg\/ \u226450 100 100 200 165 mL (for 5% mcg\/mL IgA mcg\/mL 46 mcg\/mL 46 mcg\/mL <25 \u2264140 preparation) 106 mcg\/mL Not 80 mcg\/mL Not (average) (average) mcg\/mL mcg\/mL (average) specified (average) specified Sugar Contains Contains Contains Contains 20 mg\/mL Contains Maltose Contains Contains Maltose content no carbo- no carbo- no carbo- no carbo- glucose no carbo- 90 mg\/mL no carbo- no carbo- 79 mg\/mL Osmolality hydrate hydrate hydrate hydrate (in 5% hydrate hydrate hydrate (mOsmol\/kg) stabilizers stabilizers stabilizers stabilizers solution) stabilizers stabilizers stabilizers 258 258 320 240-310 240-300 Not indicated Not indicated 310-380 280-292 310-380 Form Liquid Liquid Liquid Liquid Lyophilized Liquid Liquid Liquid Liquid Liquid Route of IV\/SC IV\/SC IV IV IV SC IV IV SC SC adminis- tration * C\u0007 onsult appropriate package insert for more details, or for information on other products that may be supplied if licensed products are not available. Cost In 2021-2022 n\t\u0007IVIG costs $60 per gram, depending on Canada (minus Quebec) US$ exchang\u00ade rate. used 6,809 kg at a cost \t u\t\u0007A single course of treatment for a 70 kg of 450 million dollars. patient with the commonly prescribed dose of 1 g\/kg each day for 2 days, costs $8,400. 106","Availability & Consumption IN ONTARIO Erythropoietin n\t\u0007Approximately 10-15% of the IVIG and Medical Patients In Ontario, requests for IVIG used in Canada is derived from for infusion are required Canadian plasma.275 to be made on a MOH \u2013 mandated request form. n\t\u0007The rest is derived from paid U.S. donors. The IVIG request form can be found at https:\/\/ n\t\u0007Canada has one of the highest per capita transfusionontario.org\/en\/ consumption rates of IVIG in the world.276 category\/ivig-scig\/ordering-ig- in-ontario\/ Immunoglobulin consumption in select countries in 2017 (in grams per 1,000 population) Australia 275.1 Fractionated Blood Products United States 247.6 Canada 232.6 France United Kingdom 165.4 113.4 Germany 104.5 Spain 86.8 Italy 84.1 Japan 43.5 43.4 Turkey South Korea 36.3 China 20.2 Sickle Cell Disease Brazil 16.3 India 3.1 0 50 100 150 200 250 300 IG consumption in grams per 1,000 population Five-Year Utilization Trend in Canada IVlg SCIg lg sufficiency (%) Manufacturing n\t\u0007IVIG is manufactured from pooled plasma obtained from several thousand donors per pool. n\t\u0007T\u0007 he constituent plasma units are tested for human immunodeficiency virus (1 and 2), hepatitis B, hepatitis C, human T-cell lymphotropic virus (I and II), hepatitis A and parvovirus B19. n\t\u0007The process includes rigorous viral inactivation steps (e.g., caprylate, low pH, chromatography, solvent detergent treatment). n\t\u0007There is no evidence of transmission of prion disease (e.g., variant CJD) through IVIG. n\t\u0007Steps in manufacturing are believed to reduce the risk of transmission of prion disease.277 107","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) B Administration & Infusion Recommendations Administration n\t\u0007For detailed recommendations for infusion of IVIG, refer to \u201cIntravenous Immune Globulin Toolkit for Ontario\u201d.278 n\t\u0007Administered as 5%, 10%, 16.5% or 20% solution as per brand specifications, dispensed by the Hospital Transfusion Service. n\t\u0007Safe for use in pregnancy. \t Refer to package insert for further details. General Principles DOSE CALCULATOR n\t Refer to Institution specific policies. https:\/\/ivig.transfusionontario. n\t\u0007Use Adjusted Body Weight Dosing org\/bmi\/ Calculator278, check every 6 months or if significant weight change. n\t\u0007Round dose to nearest vial size. Pre-infusion n\t\u0007Verify documentation of order, clinical indication and consent. n\t\u0007Identify patients at risk for complications, especially TACO (see page 56) and thromboembolic events. n\t Assess patient and check vital signs. Infusion n\t\u0007Slow initial rate for first 30 minutes refer to \u201cIVIG and SCIG infusion rates\u201d table. n\t Assess patient and check vital signs. n\t\u0007Increase rate and monitor vital signs as per institutional policy. n\t\u0007Monitor for signs of adverse reactions and report according to institutional policy. Post-infusion n\t\u0007Complete documentation including dose, brand and lot number. n\t\u0007Report and return to the hospital transfusion service any unused or defective vials, and any vials associated with an adverse event. 108","IVIG AND SCIG INFUSION RATES* Erythropoietin and Medical Patients Product Initial Rate Maximum Rate Comment Time to infuse 70 g is IGIVnex 0.6-1.2 mL\/kg\/hour Increase gradually to approximately 13\/4 hours for 30 minutes a maximum rate of 8.4 mL\/kg\/hour if Time to infuse 70 g is GAMUNEX\u2122 0.6-1.2 mL\/kg\/hour initial dose is tolerated approximately 13\/4 hours for 30 minutes Increase gradually to Use filter supplied with GAMMAGARD\u00ae 0.5 mL\/kg\/hour for a maximum rate of product 8.4 mL\/kg\/hour if SD\u2122 30 minutes initial dose is tolerated Increase gradually to a maximum rate of 4.0 mL\/kg\/hour if initial dose is tolerated GAMMAGARD\u00ae 0.5 mL\/kg\/hour Increase gradually to Fractionated a maximum rate of Blood Products Liquid for 30 minutes 8.0 mL\/kg\/hour if initial dose is tolerated Privigen 0.3 mL\/kg\/hour Product monograph Increase gradually recommends not exceeding to maximum rate 4.8 mg\/kg\/min for patients of 7.2 mL\/kg\/hour receiving >1 g\/kg OCTAGAM 0.6 mL\/kg\/hour for Increase gradually to Panzyga 30 minutes 7.2 mL\/kg\/hour 0.6 mL\/kg\/hour for Increase gradually to Maximum rate after 3 Sickle Cell Disease 30 minutes a maximum rate of infusions 7.2 mL\/kg\/hour 4.8 mL\/kg\/hour for and after 6 infusions first infusion, then if 8.4 mL\/kg\/hour. For chronic tolerated, to a maximum ITP, maximum dose of 8.4 mL\/kg\/hour 4.8 mL\/kg\/hour Hizentra 20 mL\/hour\/site 50 mL\/hour\/site No limit to the number of Cuvitru injection sites used in parallel 10-20 mL\/kg\/hour\/site for first 2 infusions Subsequent infusion rate Use up to 4 sites may be increased to simultaneously 60 mL\/hour\/site if tolerated Cutaquig First 6 infusions: Subsequent infusions: Maximum flow rate per hour 15-20 mL\/hour\/site 25\/mL\/hour\/site for all sites: \u2013 first 6 infusions 30 mL\/hour for all sites \u2013 from infusion 7, a gradual increase to 50 mL\/hour for all sites, subsequently 80 mL\/hour for all sites and, if tolerated, up to 100 mL\/hour for all sites * Refer to IVIG (Intravenous Immune Globulin) Infusion Guide and Adverse Reaction Chart for further information at https:\/\/transfusionontario.org\/en\/category\/ivig-scig\/infusion- guide-and-adverse-events\/ 109","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) B Administration & Infusion Recommendations (cont\u2019d) Adverse reactions n\t\u0007In the event of an adverse reaction, stop the transfusion and assess the patient; if the adverse reaction is minor, the transfusion may be continued at a reduced infusion rate. n\t\u0007Report all adverse reactions to your hospital transfusion service. ADVERSE REACTIONS TO IVIG 278,279,280,281 Reaction Severity Frequency** Comment\/Treatment Anxiety, chills\/ Mild- 21%282 Slow or pause IVIG treatment. Symptomatic treatment. Recurrent fever, rash, flushing, moderate reactions \u2013 pre-medicate and\/or change to another manufacturer\u2019s headache, chest, back IVIG product or where appropriate change to SCIG or abdominal pain, Stop infusion. Administer analgesics. nausea\/vomiting, Usually resolves spontaneously in 24-48 hours. Pre-medicate and\/or change tachycardia, hypo- to another manufacturer\u2019s IVIG product or where appropriate change to SCIG or hypertension Aseptic Moderate 7 in 10,000283 meningitis Migraine Mild- 3-6%284 Manage with acetominophen and\/or headache moderate NSAIDs. For recurrent reactions consider pre-medication with acetominophen, Anaphylaxis Severe Rare changing to another manufacturer\u2019s IVIG product, or where appropriate switching to SCIG. Stop infusion. May require epinephrine promptly. Consider testing for IgA and anti-IgA (see page 60) Acute kidney Severe Rare Usually with sucrose-containing product failure (none currently licensed in Canada). Predisposing factors: age >65, diabetes mellitus, pre-existing renal insufficiency Hemolysis Mild- 20% of non-group Occurs within 10 days of infusion. Severe O patients develop Non-group O patients should have their grade 2 or higher hemoglobin levels monitored post- hemolysis285 infusion, between 5-10 after infusion. Thrombo-embolic Severe 0.5-1%286 Causative relationship not clearly events established. Possibly related to increases in viscosity Neutropenia Mild- Uncommon Occurs 2-4 days after infusion and usually persists for 2 weeks287 moderate Infectious disease Severe No reported Modern viral reduction measures transmission case since HCV in are robust. Prion (vCJD) transmission 1995.288 No known remains an entirely theoretical risk case of transmission of HIV or HBV 110 ** Reactions are more likely with faster rates of infusion.","C Indications C H O O S E W I S E LY Erythropoietin and Medical Patients Immunology Immunoglobulin n\t\u0007There is good evidence to support the replacement does not Fractionated improve outcomes unless Blood Products use of IVIG in congenital and acquired there is impairment immunoglobulin deficiency, with the of antigen-specific IgG Sickle Cell Disease following conditions: antibody responses to vaccine immunizations \t u\t\u0007Significant quantitative or functional or natural infections. antibody deficiency that has been Isolated decreases in established (see the \u201cChoose Wisely\u201d immunoglobulins (isotypes statement). or subclasses), alone, do \t u\t\u0007Clinical evidence consistent with not indicate a need defective humoral immunity for immunoglobulin (e.g., recurrent infection). replacement therapy. Exceptions include \t u\t\u0007The full text describing a scoring genetically defined\/ system to aid clinical decision making suspected disorders. regarding immunoglobulin therapy is available at ncbi.nlm.nih.gov\/ Measurement of pubmed\/23518142.289 IgG subclasses is not routinely useful in \t u\t\u0007Treatable conditions to which determining the need for antibody deficiency may be immunoglobulin therapy. secondary must be excluded. Selective IgA deficiency is not an indication n\t\u0007Subcutaneous immunoglobulin is the for administration of preferred replacement strategy as it is has several advantages (better immunoglobulin. tolerated, more convenient for patients, and is economically superior). Consult a transfusion medicine specialist or immunologist for additional information. FACTORS IN CHOOSING IVIG OR SCIG Subcutaneous Immunoglobulin (SCIG) Intravenous Immunoglobulin (IVIG) u\t\u0007Clinical response not well maintained u\t\u0007Adverse effects of IVIG u\t\u0007Good maintenance of u\t\u0007Poor venous access clinical benefit u\t\u0007Able to manage home or u\t\u0007Local reactions to SCIG self-medication u\t\u0007Patient uncomfortable with u\t\u0007Patient prefers convenience of home home or self-medication self-injection 111","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) IVIG IN IMMUNOGLOBULIN DEFICIENCY290,291 Diagnosis Efficacy\/Comment Dose Primary Immune IVIG is recommended in Adult: 0.4-0.6 g\/kg\/ Deficiency292 hypogamma globulinemia every 3-4 weeks (total IgG or IgG subclasses Secondary Immune reduced) with recurrent Pediatric: 0.3-0.6 g\/kg\/ Deficiency (SID)293 bacterial infections every 3-4 weeks Hematopoietic IVIG is recommended Monitor IgG trough level in PID patients to maintain low range Stem Cell Transplant undergoing stem cell transplant 0.4-0.6 g\/kg\/every 3-4 weeks; in primary requirements may increase immunodeficiencies294 and should be based on clinical outcomes CAR-T cell recipients295 See Figure below for recommendations 0.4-0.6 g\/kg\/every 4 weeks; on when to replace requirements may increase and should be based on clinical outcomes CAR-T Cell Recipients Serum lgG 400 - 600 mg\/dL Serum lgG > 600 mg\/dL Serum lgG \u2264 400 mg\/dL Consider lgG replacement Consider lgG replacement In patients with serious or with 400-500 mg\/kg IVIG in patients with serious recurrent infections, consider or recurrent infections checking: (particularly bacterial) \u2022\tTotal lgG, lgM, lgA \u2022\tCD19+ or CD20+ B cell counts \u2022\tlgG for S. pneumoniae \t serotypes, tetanus, diphtheria If specific antibody titers are below the protective range, consider lgG replacement or determine responses to clinical or challenge vaccines 112","IVIG IN SOLID ORGAN TRANSPLANTATION296 Erythropoietin and Medical Patients Diagnosis Efficacy\/Comment Dose Kidney transplant from IVIG is recommended to decrease 2 g\/kg\/month for 4 months living donor to whom donor-specific sensitization the patient is sensitized296 Pre-Transplant For desensitization in selected Suggested dose is Fractionated (heart)296 heart transplant recipients who up to 1 g\/kg\/month Blood Products are highly sensitized, medically until transplant Peri-Transplant urgent and unlikely to receive a (heart, lung, transplant otherwise \u2013 this should Suggested dose kidney, pancreas) be preceded by discussion at the 1 g\/kg, can give transplant program level as divided doses 297,298,299,300 if in association Solid-organ transplant recipient with a course of with donor-specific antibodies plasmapheresis identified at time of transplant surgery (heart, lung, kidney, pancreas) on virtual crossmatch \u2013 first-line agent Post-Transplant Acute antibody-mediated rejection 1 g\/kg\/dose, can in a solid-organ transplant give as divided doses 296,297,298,299,300 recipient \u2013 first-line agent if in association with a course of Chronic antibody-mediated plasmapheresis Sickle Cell Disease rejection in a solid-organ transplant recipient 1 g\/kg\/month 113","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) Hematology IVIG IN HEMATOLOGICAL DISORDERS AND BONE MARROW\/STEM CELL TRANSPLANTATION290,301,302 Diagnosis Efficacy\/Comment Dose 1 g\/kg for 1 day. Immune Thrombocytopenic (ITP) Benefit established Repeat if platelet count not >30 x 109\/L refractory to standard treatment, 1 g\/kg for 1-2 days platelet count <20 x 109\/L 1 g\/kg for 2 days ITP with persistent or life-threatening Benefit established bleeding and platelet count <50 x 109\/L 1 g\/kg; longest inter-treatment Thrombocytopenia associated with Benefit established interval consistent with maintaining HIV unresponsive to antiviral therapy, adequate platelet platelet count <20 x 109\/L or <50 x 109\/L count 1 g\/kg q3-4 months with bleeding 1-2 g\/kg over ITP in pregnancy Appropriate initial 2-5 days \t u platelet count <10 x 109\/L treatment \t u p\u0007 latelet count 10-30 x 109\/L in Maternal: 1 g\/kg weekly (In 2nd or 3rd trimester non-group O patients \t u \u0007platelet count <30 x 109\/L and monitor closely for hemolytic anemia)304 bleeding at any stage in pregnancy Infant: Give IVIG if Chronic ITP unresponsive to Use in consultation platelet transfusion alternatives (e.g., splenectomy, with an expert in ITP not immediately rituximab, thrombopoietin receptor available or there agonists, immunosuppressive agents) is no response to platelet transfusion Post-transfusion purpura Recommended as or prolonged first-line treatment thrombocytopenia (>7 days). Dose Fetal\/neonatal allo-immune Considered 1 g\/kg and reassess thrombocytopenia (F\/NAIT) standard first-line (treatment of mother or fetus)303 antenatal treatment. Considered Pediatrics adjunctive therapy n T\u0007 ransfuse platelets for newborn with to maintain platelets F\/NAIT. Appropriate over 30 x 109\/L. consultation advisable with n T\u0007 ransfuse platelets in the high-risk pregnancy setting of life-threatening and neonatal unit hemorrhage (intracranial or GI bleeding) to maintain platelets >50 (raise to 100, maintain >50)63 C H O O S E W I S E LY Don\u2019t give IVIG as first line treatment for patients with asymptomatic immune thrombocytopenia (ITP).305 114","Diagnosis Efficacy\/Comment Dose Erythropoietin and Medical Patients Pure red cell aplasia (PRCA) Considered first line therapy for Up to 2 g\/kg divided over (viral or immunologic)291,301 PRCA associated with parvovirus 2-5 consecutive days B19 occurring in an immuno- compromised patient. Reasonable option for immunologic PRCA in patients who have failed other therapies Hemolytic IVIG may be considered as Up to 2 g\/kg divided Fractionated an option among supportive over 2-5 days, short Blood Products transfusion reaction therapies for urgent situations term up to 3 months in this disorder (HTR) including hyperhemolysis in Sickle Cell Disease291 Hemolytic disease Not recommended for use in 0.5 g\/kg of the fetus management of HDFN without and newborn established hyperbilirubinemia. (Unlikely to be of benefit (HDFN)290,301,306 Recommended if total serum with ABO-hemolytic bilirubin is rising despite intensive disease of the newborn phototherapy or if level is within 34- as IVIG contains anti-A 51 umol\/L of the exchange level307 and anti-B) Sickle Cell Disease Virus associated Not recommended for routine Determine in consultation use. Option in severe life hemophagocytic threatening VAHS syndrome (VAHS)301 Rare cases of Anecdotal evidence only; consider 1 g\/kg for 2 days. auto-immune use only after failure of other Determine in consultation hemolytic anemia or treatments or in urgent situations neutropenia, auto- antibodies to factor VIII or von Willebrand factor290,291,301 Allogeneic bone IVIG is not recommended Not indicated. for routine use after HSCT. Determine in consultation marrow\/ IVIG may be considered in exceptional cases: 1) \u0007No recommended dose stem cell or duration listed; use transplant290,308,309 1) A\u0007 ctive CMV-induced in conjunction with pneumonitis following appropriate antiviral transplantation medication 2) \u0007High-risk allogeneic stem 2) \u00070.4 g\/kg weekly, cell transplantation (e.g., if starting one day before hypogamma globulinemia) transplantation and for prevention of GVHD continuing to day 100 post-transplant 115","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) Neurology IVIG IN NEUROLOGICAL DISORDERS*290,310 Diagnosis Efficacy\/Comment Dose Guillain-Barre Benefit established. Recommended Total dose of 2 g\/kg divided Syndrome as treatment option within 2 weeks over 2-5 days (adults) or (including Miller- of symptom onset for patients with 2 days (children). Evaluate Fisher syndrome severe and\/or progressing symptoms. response at 4 weeks and other May be considered as a treatment variants)311 option for relapsed patients who initially responded to IVIG Chronic Benefit established; Front-line IVIG: Total dose 2 g\/kg divided treatment is corticosteroids, over 2-5 days as induction and inflammatory consider IVIG as front-line then two to five repeated doses treatment for motor CIDP of 1 g\/kg IVIG every 3 weeks demyelinating may be required before either the patient improves or it can be polyradiculopathy decided that IVIG is ineffective. 312,313,314,315 Maintenance: The most commonly used IVIG maintenance regimen in clinical trials is 1 g\/ kg every 3 weeks, but in clinical practice lower doses and longer treatment intervals maintaining maximal sustained improvement should be considered (eg, 0.4-1 g\/kg every 2-6 weeks) SCIG: Dose: 0.4 g\/kg qweek When CIDP patients switch from IVIG to SCIG, it is reasonable to start using the same mean dose (1:1) per week. If the treatment effect is insufficient, the dose should be adjusted using reliable outcome measures.315,316 Multifocal motor Benefit established. Total dose of 2 g\/kg divided neuropathy317 Recommended as first-line therapy. Diagnosis should be over 2-5 days; Maintenance: made by neuromuscular specialist 1 g\/kg q2-4 weeks317 Myasthenia Consider for refractory 2 g\/kg over 2 days: gravis318 myasthenia gravis, life-threatening presentations maintenance therapy should be individualized319 * Other conditions where IVIG is not of proven value include paraprotein polyneuropathy, neurological vasculitides, paraneoplastic neurological syndromes and autism. 116","Diagnosis Efficacy\/Comment Dose Erythropoietin and Medical Patients Acute disseminated IVIG is an option for monophasic Adults: Total dose of encephalomyelitis ADEM when first-line therapy 2 g\/kg divided over (ADEM)290,310,320 with high-dose corticosteroids 2-5 days fails or when there are contraindications to steroid use, Pediatric: Total dose Fractionated and for treatment of relapsing of 2 g\/kg divided over Blood Products ADEM to eliminate steroid 2 days dependency or for those patients who fail to respond, or have Initial treatment: Total contraindications to steroids dose of 2 g\/kg divided over 2-5 days Lambert-Eaton IVIG is an option for treatment of LEMS. Objective evidence of Maintenance therapy: Myasthenic Syndrome clinical improvement is needed A systematic approach (LEMS)290,310 for sustained use of IVIG. should be taken to determine the minimum Pediatric Autoimmune IVIG is an option for treatment effective dose, and Sickle Cell Disease Neuropsychiatric of patients with PANDAS. continued use of IVIG Disorders Associated Diagnosis of PANDAS requires should be based on With Streptococcal expert consultation objective measures of its Infections sustained effectiveness. (PANDAS)290,310 The maximum dose of IVIG per treatment Autoimmune IVIG is an option for the course should be 2 g\/kg encephalitis321 management of autoimmune encephalitis; if no or Total dose of 2 g\/kg inadequate response to front- divided over 2 days line treatment (corticosteroids is recommended as a and IVIG) at 2-4 weeks, second reasonable option line immunosuppressive agents should be Adults: Total dose considered (rituxumab, of 2 g\/kg divided cyclophosphamide)321 over 2-5 days Pediatric: Total dose of 2 g\/kg divided over 2 days IVIG not recommended as maintenance therapy321 117","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) Neurology IVIG IN NEUROLOGICAL DISORDERS* (cont\u2019d) Diagnosis Efficacy\/Comment Dose Stiff Person\u2019s IVIG is an option for treatment Initial treatment: syndrome290,310,322 of Stiff Person syndrome if Adults: Total dose of GABAergic medications fail 2 g\/kg divided over or for patients who have 2-5 days contraindications to GABAergic medications Pediatric: Total dose of 2 g\/kg divided over 2 days NMDA IVIG is an option for treatment Maintenance therapy: Encephalitis323 of patients with NMDA. A systematic approach Diagnosis of NMDA requires should be taken expert consultation. IVIG is to determine the used in conjunction with minimum effective immunosuppressive medications dose, and continued and\/or plasmapheresis use of IVIG should be based on objective Opsoclonus-myoclonus Possible treatment option. measures of its syndrome320 Objective evidence of clinical sustained effectiveness. improvement required for Maximum dose of IVIG sustained use per treatment course should be 2 g\/kg Initial treatment: Total dose of 2 g\/kg divided over 2-5 days in adults and children Maintenance therapy: May be considered depending on response to treatment Total dose of 2 g\/kg given over 2-5 days (adults) or 2 days (children) * Other conditions where IVIG is not of proven value include paraprotein polyneuropathy, neurological vasculitides, paraneoplastic neurological syndromes and autism. 118","Rheumatology Erythropoietin and Medical Patients IVIG IN RHEUMATOLOGY Diagnosis Efficacy\/Comment Dose Idiopathic Inflammatory myopathy IVIG is indicated in patients Total dose of Fractionated Includes: Dermatomyositis with Idiopathic Inflammatory 2 g\/kg divided over Blood Products and Polymyositis myopathy as adjunctive therapy 2-5 days (adults) to corticosteroids and\/or a steroid or 2 days (children); 324,325,326 sparing agent in patients with maintenance Idiopathic Inflammatory myopathy therapy should Systemic lupus who have failed first-line therapy be individualized erythematosus**327 or as clinically indicated in the Kawasaki disease328 management of severe disease Current evidence does 2 g\/kg x 1 day not support use Benefit established ** For immune thrombocytopenia associated with systemic lupus erythematosus, see Hematology. Dermatology IVIG IN DERMATOLOGY Sickle Cell Disease Diagnosis Efficacy\/Comment Dose Toxic epidermal necrolysis 329 No reliable evidence to support 2-3 grams per kg Pemphigus vulgaris benefit or lack of benefit; if used, divided over and variants333 2-3 days331,332 it should be under the supervision Epidermolysis bullosa acquisita334 of a specialist in toxic epidermal necrolysis330,331 Bullous pemphigoid335 Consider IVIG when there is no Total dose of 2 g\/ response or a contraindication kg divided over 2-5 to corticosteroids and days. Maintenance immunosuppressive agents treatment should be individualized Anecdotal evidence supports use Total dose of 2 g\/ of IVIG as adjunctive or second- kg divided over 2-5 line treatment if conventional days. Maintenance treatment is ineffective treatment should be individualized IVIG may be considered as third Total dose of 2 g\/ line therapy if patient has failed kg divided over 2-5 conventional immunosuppressants and days. Maintenance rituxumab; recommended for patients treatment should at high risk of adverse events from be individualized first and second line treatments 119","FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG) and Subcutaneous Immunoglobulin (SCIG) Obstetrics and Gynecology IVIG IN OBSTETRICS AND GYNECOLOGY 336 Diagnosis Efficacy\/Comment Dose Uncertain benefit Determine in consultation Anti-phospholipid with high-risk pregnancy syndrome337,338 specialist Not indicated Recurrent spontaneous Ineffective339 abortion Ineffective340 Not indicated In Vitro fertilization\/ implantation procedures Infectious Diseases IVIG IN BACTERIAL INFECTION 290,291 Diagnosis Efficacy\/Comment Dose 1 g\/kg on day one and Septic\/Toxic Shock Uncertain benefit; use in 0.5 g\/kg on days 2 and Syndrome (Group A consultation with experts 3 or 0.15 g\/kg per day streptococcal sepsis in infectious diseases over 5 days with hypotension and multi-organ Not recommended failure) for use Not recommended 341,342,343,344,345,346,347,348 for use Necrotizing fasciitis 349 No benefit Sepsis in patients in No benefit critical care 345,346 n\t\u0007Bone marrow transplant and red cell aplasia due to parvovirus B19: see Hematology. n\t\u0007Specific hyper-immune globulins are available from Canadian Blood services for the listed conditions: https:\/\/professionaleducation.blood.ca\/en\/immune- globulin-products (see package insert for details) \t u\t\u0007Varicella-Zoster Immune Globulin (VZIG) \t u\t\u0007Hepatitis B Immune Globulin (HBIG; BayHepB) \t u\t\u0007Anti-RSV Immune Globulin (Respigam\u00ae) \t u\t\u0007Cytomegalovirus Immune Globulin (CMVIG, Cytogam\u00ae). 120","Dosing of IVIG for Obese Patients 350 DOSE CALCULATOR Erythropoietin and Medical Patients The dose of IVIG varies depending on the https:\/\/transfusionontario.org\/ clinical condition. In general, the dose is en\/category\/ivig-scig\/dosing- based on the patient\u2019s weight. In the case using-adjusted-body-weight\/ of obese patients, the appropriate dosing regimen is unclear. It is suggested that Fractionated patients weighing more than 100 kg and Blood Products with a body mass index greater than 30 kg\/m2 should have their IVIG dose calculated using an adjusted body weight. The adjusted weight takes into account the increased volume of distribution in these patients (because of increased body fluids) without accounting for the increase in weight from body fat. A tool which assists with the calculation of the appropriate dose of IVIG based on the patient\u2019s sex, height and weight is available at https:\/\/ transfusionontario.org\/en\/category\/ivig-scig\/ dosing-using-adjusted-body-weight\/. Requests for IVIG for infusion in Ontario !A T T E N T I O N Sickle Cell Disease Requests for IVIG for infusion are required IVIG in Ontario can only to be submitted on the Request Form be requested using the prescribed by the MOHLTC. The form prescribed request form. and the protocol for its use are posted at www.transfusionontario.org. 121","FRACTIONATED BLOOD PRODUCTS: Prothrombin Complex Concentrates A Basics 351,352 Prothrombin complex concentrates (PCCs) are coagulation factor concentrates that contain factors II, VII, IX, X. The amount of the individual coagulation factor levels varies with the specific preparations. Manufacturing n\t\u0007The factor concentrate is made from pools of 1,000-2,000 plasma donations. n\t\u0007PCCs are a blood product and informed consent is required. n\t\u0007Plasma units are tested for HIV (1 and 2), hepatitis B, hepatitis C. n\t\u0007Manufacturing processes include viral inactivation steps. Products available n\t\u0007PCCs are supplied by CBS and HQ. n\t\u0007Two prothrombin complex concentrates are licensed in Canada: Octaplex\u00ae and Beriplex\u00ae. COAGULATION FACTOR LEVELS (IU\/ML) IN PCCS 352 Product Manu- Factor Factor Factor Factor Protein Protein AT III Heparin II VII IX X C S facturer 0.1 6.0 31.4 16.1 22.3 24.4 22.2 12.0 0.6 0.5 Octaplex\u00ae Octa- pharma Beriplex\u00ae CSL 31.0 16.2 28.9 41.3 21.6 17.9 Behring 122","B Monitoring & Infusion Practices for Octaplex\u00ae and Beriplex\u00ae 351 Erythropoietin How and Medical Patients n\t\u0007Lyophilized powder must be reconstituted for administration. Fractionated n\t\u0007Final volume is either 20 mL per vial Blood Products which contains 500 IU of factor IX or 40 mL per vial which contains 1000 IU Sickle Cell Disease of factor IX. n\t\u0007Can be prepared in syringe or minibag for intravenous infusion. 123","FRACTIONATED BLOOD PRODUCTS: Prothrombin Complex Concentrates B Monitoring & Infusion Practices for Octaplex\u00ae and Beriplex\u00ae (cont\u2019d) Monitor patient n\t\u0007Check patient\u2019s vital signs prior to starting, 15 minutes after starting, at end of transfusion and if there are any transfusion reactions. n\t\u0007Repeat INR immediately postinfusion to ensure adequate correction of INR. n\t\u0007Effective half life of PCC is approximately !A T T E N T I O N 6 hours. Giving plasma for warfarin WARFARIN REVERSAL AND TREATMENT OF VITAMIN K DEFICIENCY reversal is associated with n\t\u0007Emergency reversal of warfarin effect. a 3-fold higher risk \t u\t\u0007For patients with INR \u22651.5 AND of TACO.353 \t u\t\u0007\u201cLife or limb\u201d threatening bleeding OR \t u\t\u0007Emergency surgery within 6 hours !A T T E N T I O N \tGive: \t u\t Vitamin K 10 mg IV Vitamin K should be given \t u\tPCC intravenously at same time as PCCs to avoid rebound Dose351 anticoagulation. n\t\u0007The National Advisory Committee INR\t PCC DOSE on Blood and Blood Products (NAC) Recommendations on dosing are <3 1,000 IU based on the INR as detailed in the table to the right. 3-5 2,000 IU >5 3,000 IU n\t\u0007If the INR is unknown and major bleeding https:\/\/www.nacblood.ca\/ is present, 2,000 IU (80mL) should be resources\/guidelines\/PCC.html administered. n\t\u0007The published NAC Recommendations include a table of detailed dosages based on a combination of INR and body weight, as an alternative dosing strategy. n\t\u0007The maximum dose should not exceed 3,000 IU. When n\t\u0007Infusion rate should not exceed 1000 IU per 5 minutes. 124","Storage C H O O S E W I S E LY Erythropoietin n\t\u0007Store between +2 to +25\u00b0C. and Medical Patients PCCs should not be n\t\u0007Freezing and light exposure may affect administered in clinical product quality. situations where vitamin K alone will suffice. n\t\u0007PCCs should NOT be administered if: Situation Vitamin K Fractionated \t u\t\u0007INR \u22641.5 as individual coagulation dose\/route Blood Products factors are not below the level needed INR >8-10, 2 mg PO to maintain hemostasis. no bleeding Surgery >6 10 mg IV \t u\t\u0007Patients with known HIT (Beriplex\u00ae hours later and Octaplex\u00ae both contain heparin). Non-critical 1 mg IV bleeding n\t\u0007Clinical situations where vitamin K alone will suffice are shown in the \u201cChoosing Wisely\u201d box to the right. REVERSAL OF OTHER ANTICOAGULANTS Sickle Cell Disease n\t\u0007Reversal of anti-Xa inhibitors. \t u\t\u0007Currently specific reversal agents are not available in Canada. \t u\t\u0007PCCs at a dose of 2,000 IU (repeated in 1 hour if hemostasis is not achieved) is being used across Canada. \t u\t\u0007Data to support its use is limited to observational and uncontrolled studies.354 n\t\u0007Reversal of anti-IIa inhibitors (Dabigitran).355 \t u\t\u0007A licensed antidote (Idarucizumab, Praxbind\u00ae) is available in Canada. \t u\t\u0007The dose of Idarucizumab is 5 g, administered in two 2.5 g bolus infusions each over 5 minutes, not more than 15 minutes apart. 125","FRACTIONATED BLOOD PRODUCTS: Fibrinogen Concentrate A Basics How n\t\u0007Lyophilized powder must be reconstituted for administration. n\t\u0007Final volume is 50 mL per vial which contains 1 gram of fibrinogen. n\t\u0007Can be prepared in a syringe or minibag for intravenous infusion. n\t\u0007Cryoprecipitate is also a source of fibrinogen replacement but fibrinogen concentrates are clinically equivalent and the preferred product for both congenital and acquired hypofibrinogenemia. n\t\u0007Fibrinogen concentrates have a superior safety profile as a pathogen inactivated product, and logistical advantages with respect to dosing, storage and administration. Dose n\t A\u0007 dults: 4 grams infused over 10 minutes for bleeding patients.356 n\t N\u0007 eonates and Children: 50 mg\/kg infused over 10 minutes for bleeding patients.18 Storage n\t\u0007Store between +2 to +25C for Fibryga\u00ae (for up to 36 months) +2 to +8C for RiaSTAP\u00ae (for up to 60 months). n\t\u0007Ideally give immediately following reconstitution; may be stored at room temperature and infused. Monitoring n\t\u0007Monitor patient for signs and symptoms of allergic transfusion reactions. n\t\u0007Repeat fibrinogen level immediately post-infusion. 126","B Indications Erythropoietin and Medical Patients n\t\u0007For major or massive hemorrhage from surgery or trauma when fibrinogen <1.5 g\/L.18, 357 n\t\u0007For acute phase of acute promyelocytic C H O O S E W I S E LY Fractionated leukemia with fibrinogen <1.5 g\/L.358 Blood Products Don't transfuse Fibrinogen n\t\u0007Hemorrhage after cardiac surgery or concentrates for: peripartum with fibrinogen <2.0 g\/L.18 u D\u0007 IC with low fibrinogen n\t\u0007Intracranial hemorrhage secondary to level in the absence of treatment with Tissue Plasminogen bleeding or a planned Activator with fibrinogen <2.0 g\/L. procedure (other than the acute phase of acute n\t\u0007Congenital afibrinogenemia or promyelocytic leukemia) hypofibrinogenemia for bleeding or prior to procedures. MASSIVELY BLEEDING PATIENTS WHERE Sickle Cell Disease PLASMA IS UNAVAILABLE n\t\u0007Some smaller\/remote organizations may be unable to provide plasma in bleeding patients. n\t\u0007Can be given concurrently as a substitute for plasma, where plasma is not available. n\t\u0007Dosing strategies are inconclusive: with 2000 IU (or 25 IU\/kg rounded up for pediatric patients) of PCC suggested. 127","FRACTIONATED BLOOD PRODUCTS: RhIG Rh(D) Immune Globulin (WinRho\u00ae) 359,360,361 !A T T E N T I O N Purpose Rh immunoglobulin is a n\t\u0007Prevention of immunization in Rh(D) blood product: informed negative patients exposed to Rh(D) consent is required. positive red cells. Dosages Available n\t\u0007120 ug (600 IU), 300 ug (1,500 IU), 600 ug (3,000 IU), 1,000 ug (5,000 IU), IV or IM. Prevention of Rh(D) immunization by Rh(D) positive fetal red cells in pregnancy in non-sensitized Rh(D) negative females: n\t\u0007Recommended doses: \t u\t\u0007Prophylactic dose at 28 weeks 300 ug IV or IM. \t u\t\u0007Post-partum, newborn Rh(D) positive (including weak D), 300 ug IV or IM, within 72 hours of delivery (give as soon as possible if 72 hour deadline is missed). \t\t \u2022\t\u0007Quantify feto-maternal hemorrhage; additional doses of RhIG required if fetomaternal hemorrhage present (dose should be calculated by using the College of American Pathologists\u2019 on line calculator at https:\/\/uchicagomedlabs.testcatalog.org\/ catalogs\/367\/files\/7215) \t u\t\u0007Complications of pregnancy: \t\t \u2022\t\u0007Pregnancy before 12 weeks, 120 ug IV\/IM \t\t \u2022\t\u0007Pregnancy 12-20 weeks, 300 ug IV\/IM \t\t \u2022\t\u0007Pregnancy after 20 weeks, 300 ug IV\/IM \t\t\t \u2013 P\u0007 lus Fetal Maternal Hemorrhage (FMH) testing to determine if additional doses required 128","n\t\u0007Complications of pregnancy requiring Rh(D) Erythropoietin immune globulin: and Medical Patients \t u\t\u0007Antepartum hemorrhage Fractionated \t u\t\u0007Amniocentesis, chorionic villus biopsy Blood Products or cordocentesis Sickle Cell Disease \t u\t\u0007External cephalic version, abdominal trauma \t u\t\u0007In-utero therapeutic interventions \t u\t\u0007Ectopic pregnancy, intrauterine death and stillbirth \t u\t\u0007Abortion; threatened, actual or therapeutic. n\t\u0007Immunization with other red cell antigens: \t u\t\u0007Severe hemolytic disease of the fetus and newborn may involve many antigens other than Rh(D), including, but not restricted to, Rh C, c, E,e , K, k, Fya, Jka, Jkb and S. \t u\t\u0007Specific immune globulin prophylaxis is not available for specificities other than Rh(D). Other indications for treatment\/prophylaxis with Rh(D) immune globulin: n\t\u0007After transfusion of platelet components from Rh(D) positive donors. \t u\t\u0007ONLY to Rh(D) negative patients of childbearing potential. \t u\t\u0007The presence of \u201cpassive\u201d anti-D complicates red cell compatibility testing and may delay transfusion without significant benefit. \t u\t\u0007The risk of Rh(D) immunization by platelet components is about 1%.49,362 Note: RhIG contains IgA at a concentration of 40 ug\/mL or less. 129","SICKLE CELL DISEASE A Principles of Transfusion in Sickle Cell Disease363 Decisions regarding the transfusion of patients !A T T E N T I O N with sickle cell disease are made very differently from those of other patients and are rarely Indications for transfusion determined by the hemoglobin alone. In in patients with sickle cell addition, patients with sickle cell disease disease differ significantly are at increased risk of serious transfusion reactions. For this reason, consultation with from other patients. a hematologist is strongly recommended before blood products are administered. Three principles of transfusing patients !A T T E N T I O N with sickle cell disease can be summarized In the absence of as follows: symptoms, transfusion should be avoided unless 1. \u0007The primary benefit of transfusion is from decreasing the HgbS% (as determined by the hemoglobin has hemoglobin electrophoresis) rather than decreased to <50 g\/L.364 increasing the total hemoglobin. !A T T E N T I O N 2. \u0007Transfusing above a hemoglobin threshold of 100 g\/L is likely to worsen oxygen Never transfuse a sickle cell delivery due to hyperviscosity. patient to a hemoglobin >100 g\/L. 3. \u0007W\u0007 hile a hemoglobin < 50 g\/L is a strong indication for transfusion in sickle cell patients, several conditions that can cause anemia of this severity (aplastic crisis, sequestration crisis and hyperhemolysis) also increase the risk of serious transfusion reactions. B Special Transfusion Requirements AT T E N T I O N n\t\u0007To prevent dangerous hemolytic !Life-saving transfusion transfusion reactions, blood products for patients with sickle cell disease must be should not be withheld selected with greater care than is expected if prophylactically with other patients. phenotype-matched RBCs n\t\u0007Specifically, RBC units should be selected on are not available. the basis of the patient\u2019s extended antigen phenotype (supported whenever possible by genotyping studies), and the presence of any RBC antibodies which may have developed in the past. In some cases, this information will reveal that RBC units of rare phenotype will need to be ordered from the blood supplier. 130","u\t\u0007As the above steps may introduce !A T T E N T I O N Erythropoietin delays in care, it is important that the and Medical Patients hospital transfusion service be notified, Notify hospital transfusion even if there is not an immediate plan service immediately about Fractionated to transfuse, every time a sickle cell sickle cell disease patients. Blood Products patient presents for acute care. This notification should include a list of !A T T E N T I O N Sickle Cell Disease other hospitals the patient has received care at previously (this information may Patients with sickle cell be included within the \u2018comments\u2019 disease must be issued a section attached to a request to card with their extended perform a blood group and screen). phenotype and specificities \t u\t\u0007Note that the above considerations of any alloantibodies apply to all forms of sickle cell disease present. The reason for (ie., HgbSS, HgbSC and HgbS-\u00df- and importance of the card thalassemia). No special precautions must be clearly explained are required, however, for patients with sickle cell trait (ie., Hgb AS). to the patient The role of genotyping n\t\u0007While serologic techniques can identify common minor blood group antigens (D,C,c,E,e,Fya,Fyb,M,N,S and s) they cannot identify the partial variants of these antigens which are common in these patients. \t u\t\u0007For example, studies have found that nearly a quarter of sickle cell patients who phenotype as C-positive only express a partial form of this antigen. Transfusing these patients C-positive RBC units therefore risks provoking an anti-C antibody, which is capable of causing life-threatening transfusion reactions.365 n\t\u0007Genotyping can also identify patients who may be safely challenged with antigens they don\u2019t express on their own RBCs. For example, a large majority of sickle cell patients who phenotype as Fyb-negative are actually Fyb-positive by genotype, but with expression limited to non-erythroid cells. These patients can be safely transfused Fyb-positive RBCs.366 131","SICKLE CELL DISEASE B Special Transfusion Requirements (cont\u2019d) n\t\u0007Genotyping studies are available at no charge Indications for from Canadian blood suppliers (Canadian top-up transfusion Blood Services and HemaQuebec). 1. Hemoglobin < 50 g\/L unless Sickledex\u00ae-negative blood secondary to hyperhemolysis n\t\u0007RBC units which test positive by Sickledex\u00ae 2. Mild-moderate acute chest test are from donors with sickle cell trait syndrome (HgbAS). This blood would be safe to 3. Pre-operative prophylaxis in administer to patients with sickle cell disease, but it will confound post-transfusion patients with hemoglobin measurements of the patient\u2019s HgbS% < 90 g\/L, without high-risk and should be avoided, if possible.367 features, undergoing low- moderate risk surgery C Exchange Transfusion Indications for n\t\u0007Depending upon a patient\u2019s initial exchange transfusion: hemoglobin, it may not be possible to 1. \tSevere acute chest syndrome achieve a specific target HgbS% by top- up transfusion without exceeding a total (e.g., accompanied by hemoglobin of 100 g\/L. multiorgan failure) 2. \tTreatment of acute ischemic n\t\u0007Exchange transfusion may therefore be required stroke to meet the desired target of HgbS% <30% 3. \tSecondary stroke prophylaxis (Note: in patients with HgbSC, this goal may 4. \tPrimary stroke prophylaxis be reframed as targeting a HgbA > 70%). 368 in patients at high risk (e.g., high-flow transcranial doppler n\t\u0007Ensure patient is euvolemic before ultrasound) initiating an exchange. 5. \tPre-operative prophylaxis in high-risk patients or n\t\u0007Automated red cell exchange may be patients undergoing high-risk available at specialized centres. procedures 6. \tProgressive cholestasis Manual\/partial exchange: 7. \tPost-solid organ transplant n\t\u0007A typical protocol (for children, smaller 8. \tHigh-risk pregnancy 9. \tOther complications (e.g., comparable volumes, e.g., 10 mL\/kg):369 pulmonary hypertension, priapism, acute renal failure, \t 1.\t\u0007Phlebotomize 1st 500 mL of whole blood malleolar ulceration) failing (for patients who are very anemic at to respond to more targeted baseline [e.g., hemoglobin <70 g\/L], a therapy top-up transfusion may be required 10. Patients with progressive before first phlebotomy) complications despite top-up transfusion \t 2.\t Bolus 500 mL of 0.9% normal saline 11.\tPrevention of pain crises or acute chest syndrome \t 3.\t\u0007Phlebotomize 2nd 500 mL of whole blood in patients failing or with contraindication to \t 4.\t Transfuse 2 units of RBCs hydroxyurea. 12.\tPatients requiring top-up \t 5.\t\u0007Repeat as necessary to achieve target transfusions with hemoglobin HgbS% (typically a 1.5 blood volume > 90 g\/L exchange is necessary for first treatment; 132","single volume cycle may be adequate Erythropoietin for maintenance therapy). Note and Medical Patients that for patients starting with Hgb near 100 g\/L, step 4 should alternate between transfusion of 1 and 2 units in order to keep total hemoglobin from exceeding 110 g\/L. D Primary indications for Transfusion THERAPEUTIC TRANSFUSION Fractionated Blood Products Aplastic Crisis370 !A T T E N T I O N n\t\u0007Most commonly due to parvovirus Sickle Cell Disease Due to decreased lifespan B19 infection, with profound of sickle RBCs (16-20 days), reticulocytopenia. significant fall in hemoglobin n\t\u0007Transfusion support may be required will occur before the if symptomatic anemia, or if reticulocyte count recovers.372 hemoglobin <50 g\/L. !A T T E N T I O N n\t\u0007Due to a compensatory increase in In people with hypovolemia plasma volume, transfuse slowly to due to severe acute splenic avoid volume overload and consider sequestration, immediately pre-transfusion diuretic. provide IV fluid resuscitation. Sequestration crisis In consultation with a sickle cell n\t\u0007Trapping of sickle erythrocytes in splenic expert, transfuse people who have acute splenic sequestration sinusoids resulting in massive, painful and severe anemia to raise the enlargement of spleen and severe hemoglobin to a stable level, anemia over a period of hours. while avoiding over-transfusion. n\t\u0007If untreated, sequestration crises cause In consultation with a sickle cell death from hypovolemic shock\/anemia; expert, address the performance immediate transfusion often required. and timing of splenectomy in n\t\u0007Post-transfusion hemoglobin levels people with recurrent acute often higher than expected, suggesting autotransfusion as sequestered RBCs splenic sequestration or released back into circulation. symptomatic hypersplenism.373 n\t\u0007To avoid accidental polycythemia and hyperviscosity, transfuse 1 unit at a time, reassessing hemoglobin. Pediatrics In children, consider administering RBCs in smaller than normal aliquots (e.g., 3-5 mL\/kg). Often a single transfusion is sufficient to reverse a sequestration crisis.371 133","SICKLE CELL DISEASE n\t\u0007Less commonly, patients may present with hepatic sequestration crisis, characterized by a rapidly enlarging liver accompanied by a decrease in hemoglobin, a rise in reticulocyte count, and a conjugated hyperbilirubinemia. \t u\t\u0007This type of sequestration is generally less severe than splenic sequestration but can have first onset in adulthood. \t u\t\u0007Transfusions should also be administered cautiously due to the risk of autotransfusion and hyperviscosity. Recurrences are common.364 Acute chest syndrome374 !A T T E N T I O N Acute chest syndrome n\t\u0007Transfusion is advised in patients with is defined as new moderate to severe acute chest syndrome; pulmonary infiltrates exchange transfusion rather than a top-up on chest x-ray in a transfusion is indicated in patients with patient with sickle cell severe disease (e.g., rapid deterioration disease, accompanied by or evidence of multiorgan dysfunction) or in those with a baseline hemoglobin > 90 respiratory symptoms, g\/L. Otherwise, a top-up transfusion to a chest pain or fever. Acute maximum of 100 g\/L may considered as chest syndrome cannot be initial therapy. easily distinguished from, and is often accompanied n\t\u0007In patients with milder disease (e.g., chest by, community-acquired x-ray infiltrates without hypoxemia), supportive care without transfusion may pneumonia. be considered. n\t\u0007In all cases, supportive care should include antibiotics with coverage for atypical organisms, and consideration for incentive spirometry and\/or bronchodilators. n\t\u0007Any sickle cell patient requiring invasive ventilatory support should be referred to a centre capable of providing apheresis exchange transfusion support. 134","Progressive cholestasis (aka sickle hepatopathy) Erythropoietin n\t\u0007Syndrome marked by right upper quadrant and Medical Patients pain, extreme elevation of bilirubin and Fractionated alkaline phosphatase, and variable elevation Blood Products in transaminases. \t u\t\u0007May be accompanied by renal failure, Sickle Cell Disease thrombocytopenia, and prolonged coagulation times. \t u\t\u0007Without prompt institution of exchange transfusion, patient may progress to fulminant liver failure.374 \t u\t\u0007Avoid liver biopsy due to high risk of complications. Acute ischemic stroke or retinal artery occlusion n\t\u0007All patients should be initiated on a program of monthly transfusions with the goal of keeping HgbS < 30%. n\t\u0007The same practice should be followed with adult patients, although there is less supporting evidence and consideration should be given to other potential causes of ischemic stroke (e.g., cardioembolism). n\t\u0007In patients with hemorrhagic stroke secondary to underlying vasculopathy, implementation of regular transfusion support may be beneficial for secondary stroke prevention once the bleeding has resolved. 135","SICKLE CELL DISEASE PROPHYLACTIC Perioperative n\t\u0007Due to high rates of perioperative complications (e.g., 10% rate of acute chest syndrome typical onset 2-3 days post- operatively) aggressive supportive care and close observation is indicated.375,376 \t u\t\u0007Avoid surgery during vaso-occlusive episodes \t u\t\u0007IV fluids if NPO \u22652 hours pre-op and continue post-op until oral fluids tolerated \t u\t\u0007Maintain SpO2 >96% and encourage incentive spirometry \t u\t\u0007Avoid hypothermia \t u\t\u0007Favour laparoscopic approaches \t u\t\u0007Post-operative prophylaxis for deep venous thrombosis if immobile >24 hours \t u\t\u0007Aggressive control of pain \t u\t\u0007Early mobilization n\t\u0007The type and intensity of pre-operative transfusion depends upon three variables: (see table) \t u\t\u0007the risk of the procedure \t u\t\u0007the patient\u2019s baseline comorbidities \t u\t\u0007the patient\u2019s baseline hemoglobin. n\t\u0007Pre-operative transfusions (whether top-up or exchange) should be performed within 10 days of the surgical procedure. 136","Surgical Procedure Transfusion Management Erythropoietin Transfusion likely not necessary and Medical Patients Low risk: Skin, minor dental, perineal, or distal extremity surgery Hgb <90 g\/L top up to 100 g\/L; Hgb >90 g\/L exchange to HgbS<60% Moderate risk: Abdominal, oropharyngeal Exchange transfusion likely or orthopedic surgery necessary (target HgbS<30%) High risk of serious co-morbidities: Fractionated Intracranial, cardiovascular, or intrathoracic Blood Products procedures; scleral buckle Note: in patients with HgbSC, the goal of transfusion is better expressed as a target HgbA%. For example, the goal for a high-risk procedure is to achieve a HgbA > 70 g\/L High Stroke Risk Sickle Cell Disease n\t\u0007In children, transfusion is indicated for secondary prevention of ischemic stroke and for primary prevention in patients with high-risk features (e.g., high middle cerebral artery or internal carotid blood flow by pediatric transcranial ultrasound). \t u\t\u0007In the latter group, maintaining HgbS <30% while keeping total hemoglobin <120 g\/L results in a 92% reduction in stroke incidence.377 n\t\u0007Children (ages 4-16) without significant cerebral vasculopathy can be safely transitioned to hydroxyurea after 12 months of transfusion if they have no prior history of stroke or TIA [i.e., isolated high Transcranial Doppler (TCD)]. TCD should be performed every 3 months once the switch to hydroxyurea has been done and an immediate restart of transfusion in the case of reversion.378 \t u\t\u0007Transfusion and hydroxyurea need to be overlapped by 4-9 months.379 \t u\t\u0007A safe alternative to transfusion has not yet been established in children who have already experienced a stroke. n\t\u0007Little evidence to guide initiation of transfusions for either primary or secondary stroke prophylaxis in adults. n\t\u0007Patients with silent ischemic strokes may also benefit from transfusion, with management advised on a case-by-base basis in consultation with hematology and\/or neurology. (e.g., strokes that do not lead to apparent focal neurological symptoms and can only be detected neuroimaging techniques).380 137","SICKLE CELL DISEASE E \tSupplemental indications for transfusion For the following indications a trial of transfusion therapy may be considered if non- transfusion therapies (e.g., localized treatment, disease-modifying medications, treatment of comorbidities) have been unsuccessful. 1. R\u0007 ecurrent pain episodes\/acute chest syndrome381 n\t\u0007In patients who have failed an adequate trial of hydroxyurea or other disease-modifying medication, chronic transfusion support !A T T E N T I O N may be considered as a means of decreasing recurrence of vaso-occlusive pain episodes Transfusion not indicated as or acute chest syndrome.380,382 treatment of uncomplicated n\t\u0007Transfusion not indicated as treatment acute vaso-occlusive pain of uncomplicated acute vaso-occlusive episodes. pain episodes, or for treatment of chronic pain syndromes (e.g., avascular necrosis, osteomyelitis, neuropathic pain).371,383 !A T T E N T I O N While the American Society 2. Priapism of Hematology acknowledges n\t\u0007Transfusion may be of benefit for episodes there is insufficient evidence to recommend a strategy of lasting >4 hours, unresponsive to aspiration prophylactic transfusion rather of blood from the corpora cavernosa and than standard care in pregnant irrigation with dilute epinephrine.384,385 3. Malleolar ulcers sickle cell patients, prophylactic transfusion at regular intervals n\t\u0007Transfusion may speed healing if no at the onset of pregnancy should response to bed rest, wound care, nonetheless be considered for antibiotics, hyperbaric oxygen.386 women with: a history of severe 4. Pregnancy363,387 sickle cell-related complications before the current pregnancy n\t\u0007Although hydroxyurea is contraindicated in pregnancy, the role of transfusion (including during previous is unclear. pregnancies) with the goal of reducing recurrent pain episodes n\t\u0007A single RCT of transfusion support to or other complications in the maintain the maternal HgbS <35% did mother, and additional features not result in improved fetal outcomes of high-risk pregnancy (e.g., compared to a strategy of transfusing nephropathy), with the goal only if hemoglobin <60 g\/L accompanied by of improving fetal outcomes. a reticulocyte response of <3%.382 However, Moreover, women who develop maternal sickle cell complications were SCD-related complications during nonetheless decreased.382 the current pregnancy may benefit from initiating regular transfusion. 138","5. Pulmonary hypertension388 !A T T E N T I O N Erythropoietin Priapism, pulmonary and Medical Patients n\t\u0007Defined as a resting mean pulmonary hypertension and malleolar pressure (mPAP) > 20 mmHg on right heart catheterization. An increased tricuspid ulcers may represent regurgitant jet velocity (TRV) \u22652.5m\/sec complications of chronic is associated with increased morbidity and intravascular hemolysis mortality but is only a screening tool for (e.g., nitric oxide depletion) pulmonary hypertension, which requires a pulmonary artery catheterization to both rather than acute confirm the diagnosis and to distinguish vaso-occlusion.388 pre- from post-capillary causes. Fractionated n\t\u0007In patients with TRV of >2.5 m\/s, Blood Products NT-pro-BNP >160 pg\/ml, or pre-capillary pulmonary hypertension (i.e., pulmonary arterial hypertension) confirmed by right heart catheterization, chronic transfusion therapy should be considered if lack of response (or contraindication) to treatment with hydoxyurea.388 Sickle Cell Disease 139","SICKLE CELL DISEASE F \tTransfusion Complications Delayed hemolytic transfusion reactions !A T T E N T I O N n\t\u0007Without prophylactic phenotypic matching, Alloimmunized sickle cell patients require an alloimmunization rates of 19 to 43% have been reported in transfused sickle cell disease antibody card. patients, with the majority of antibodies directed towards the C, E and K1 antigens.371 !A T T E N T I O N \t u\t\u0007Alloimmunization is due in part to genetic Continuing to transfuse differences in the antigens expressed on a patient with RBCs in the donor population (primarily Caucasians) vs. recipients. hyperhemolysis may cause worsening n\t\u000730-50% of antibodies will be undetectable of anemia! on retesting within the year; patients may be inadvertently challenged with subsequent transfusions, resulting in delayed hemolytic transfusion reactions.367 n\t\u0007Prophylactic matching for antigens therefore advised when selecting RBCs for sickle cell patients; advance notification of hospital transfusion service required. \t u\t\u0007Prophylactic matching decreases the rate of alloimmunization (from 3.0% to 0.5%\/unit) but it remains an issue.389 n\t\u0007Due to the high frequency of variant RBC antigens in individuals of African ethnicity, genotyping of patients with sickle cell disease is highly recommended.363 Hyperhemolysis390,391 n\t\u0007Defined as post-transfusion RBC destruction accompanied by fall in hemoglobin to below pre-transfusion levels. \t u\t\u0007Hemolytic indices increased from baseline, occasionally accompanied by relative reticulocytopenia. \t u\t\u0007Acute: occurs less than 7 days after transfusion, often with no new antibodies detectable. \t u\t\u0007Delayed: occurs between 1 and 4 weeks following transfusion and often accompanied by new RBC antibodies. n\t\u0007Enhanced hemolysis appears to involve both transfused and autologous RBCs, and may be exacerbated by further transfusion of even crossmatch compatible\/antigen-negative RBCs. 140","u\t\u0007Patients requiring emergency transfusion Erythropoietin support who are at high-risk of and Medical Patients hyperhemolysis should be considered for administration of pre-transfusion rituximab. Fractionated Blood Products n\tA\u0007 void further transfusions, if at all possible: \t u\t\u0007Treat with IVIG 2 g\/kg over 2-5 days and high dose steroids (e.g., Prednisolone 1 mg\/kg\/d x 7 days).392 \t u\t\u0007Consider brief course of erythropoietin if relative reticulocytopenia.392 \t u\t\u0007I\u0007f accompanied by acute organ failure, or if first line therapies have failed, eculizumab may be indicated.363 Hyperviscosity393 !A T T E N T I O N Sickle Cell Disease n\t\u0007Sudden onset hypertension during or shortly Patients with a hemoglobin after transfusion, accompanied by signs > 110 g\/L may require of congestive heart failure and profound alterations in mental status, including phlebotomy to decrease stupor, coma, seizures, or features of viscosity effects intra-cerebral infarct or hemorrhage.394 n\t\u0007Risk increases if hemoglobin transfused above 100-110 g\/L in patients with SCD and HgbS% >25%, particularly if patient dehydrated and hypoxemic.395 \t u\t\u0007May also occur secondary to auto- transfusion following transfusion support of sequestration crises. n\t\u0007Manage with emergency phlebotomy. Transfusional iron overload n\t\u0007Each transfused unit of RBCs delivers Iron 180 mg of iron.19 n\t\u0007Significant iron overload therefore likely Red Blood = after repeated top-up transfusions: may Cells eventually result in hepatic injury, particularly when serum ferritin 180 mg > 2500 \u00b5g\/mL or when calibrated MRI measures a liver iron concentration > 7 mg\/g dry weight.396 n\t\u0007Patients with transfusional iron overload should be followed by a hematologist with expertise in sickle cell disease for iron overload and iron chelation therapy initiated where indicated. 141","APPENDICES Price \t$421 Appendix A \t$192 \t$480 Price List397 \t$504 Item $424 1 unit red blood cells* \t$60 Pooled platelets (dose)** \t$61 Apheresis platelets (dose) \t$10 4 units frozen plasma*** \t$10 Fibrinogen Concentrates per gram \t$25 IG per gram \t$30 Albumin per 25 gram equivalent \t$558 Blood group (ABO, Rh D) \t$1,222 Antibody screen \t$86 Crossmatch (no antibody) Crossmatch (antibody positive patient) Prothrombin Complex Concentrates 1,000 IU Recominant Factor VIIa\/mg Anti-D 300 ug *\tThis cost refers only to the acquisition cost of a unit of RBC. \t The cost of delivery of a unit of blood to a patient ranges from $522 to $1,183 (US). 398 ** This cost refers only to the acquisition cost of a platelet unit. \t The total cost of a platelet is $1359.99 per unit.399 ***\tThis cost refers only to the acquisition cost of plasma. \t The total cost of plasma is $409.62 per unit or $1,608.37 per patient transfused.400 142","143 Appendices","A complete list of references for this pocket guide can be found on the ORBCoN website at https:\/\/transfusionontario.org\/en\/category\/bloody-easy-e-tools- publications\/bloody-easy-for-healthcare-professionals\/ Check out these other Bloody Easy Handbooks available: Bloody Easy Blood Administration Bloody Easy Blood Administration handbook is designed for nurses or healthcare professionals administering blood. It provides an overview of blood and blood products, the risks associated with them, and how they should be administered. In addition, it describes the types of transfusion reactions that may occur. Bloody Easy Coagulation Simplified Bloody Easy Coagulation Simplified provides practical information on coagulation. It is designed to enhance the knowledge of physicians, nurses, and medical laboratory technologists about the basics of coagulation, from laboratory testing to anticoagulant drugs and management of bleeding disorders. Design and layout by Hope Creative Inc., Toronto, Ontario Published by Ontario Regional Blood Coordinating Network Printed in Canada ISBN 978-0-9869176-2-2","Red Blood Cell Pre-Transfusion Checklist Alternatives failed or q A\u0007 nemia investigations completed (e.g., CBC, blood film, have been ordered? ferritin, iron saturation, vitamin B12, reticulocyte count) Consent? q \u0007Iron (oral and IV), vitamin B12, erythropoietin ordered Female under 45? or not indicated At risk for FATAL transfusion- Patient advised of risks of: associated Graft vs. Host Disease? q \u0007TACO 1 in 100 q Delayed reaction 1 in 2,500 Diuretics? q T\u0007 RALI 1 in 10,000 q M\u0007 ajor allergic reaction 1 in 40,000 q \u0007Bacterial infection 1 in 250,000 q O\u0007 rder Kell-negative units q I\u0007nform recipient of the potential risk of transfusion causing hemolytic disease of the newborn in future pregnancies Order irradiated blood if patient has any history of the following: q Hodgkin\u2019s lymphoma q Allogeneic or autologous stem cell transplant or CAR-T cell infusion q Ever treated with Alemtuzumab (anti-CD52), Anti-thymocyte globulin (ATG), Bendamustine, Cladribine (2-CDA), Clofarabine, Deoxycoformicin, Fludarabine, Nelarabine q Congenital immunodeficiencies Does my patient have a history of: q \u0007Age greater \u226570 years q \u0007Renal dysfunction q \u0007Left ventricular dysfunction q P\u0007 rior or current CHF q S\u0007 evere euvolemic anemia (hemoglobin <50 g\/L) q I\u0007f YES to any of the above: prescribe PO\/IV furosemide pre-transfusion (unless currently hypovolemic) Rate and Dose? q S\u0007 pecify rate of infusion (default rate is over 2 hours per unit; inpatients and patients at risk for TACO (need diuretics) infuse over 3-4 hours) q O\u0007 rder 1 unit at a time (unless bleeding) TACO: Transfusion-Associated Circulatory Overload, TRALI: Transfusion-Related Acute Lung Injury, CHF: Congestive Heart Failure",""]