Blood Transfusion Review 2/3/2018 Mahmoud Charif M.D. Associate Professor of Medicine Division of Hematology & Oncology University of Cincinnati College of Medicine

Red Cell Antigens Anti-A, Anti-B naturally occurring IgM RH No need for prior exposure RH D C E c e A B M N S P U Lutheran Le Diego Colton Dombeock LW Yt I Ch/Rg JMH Knops Xg Prior exposure necessary for antibodies IgG: Transfusion Pregnancy Kell Duffy Kidd

White Cells and Platelets Platelet specific antigens Neutrophils specific antigens Cytokines HLA antigens

Pretransfusion Testing ABO Rh-D Antibody screen (to look for antibodies to minor blood groups in the recipient‘s serum) Infectious testing: Bacterial testing of platelets Hepatitis B virus Hepatitis C virus HIV 1,2 Chagas disease Human T-Lymphotropic virus (HTLV-I/II) Syphilis West Nile virus Zika

Pretransfusion Testing ABO Rh-D Antibody screen (to look for antibodies to minor blood groups in the recipient‘s serum) Infectious testing: Bacterial testing of platelets Hepatitis B virus Hepatitis C virus HIV 1,2 Chagas disease Human T-Lymphotropic virus (HTLV-I/II) Syphilis West Nile virus Zika

Blood Components RRBCs: 42 days refrigerated: One unit raises hemoglobin by an average of 1 g/dL Platelets: 5 days at room temperature (- one day for bacterial testing) FFP: frozen for one year (by definition has 100% of clotting factors) Cryoprecipitate: FFP thawed at cold temperature allowing large proteins to precipitate, 1 FFP: 1 Cryo unit Typical dose 5-10 pooled units Fibrinogen, von Willebrand factor, factor VIII, factor XIII Primarily used for fibrinogen replacement: 70-100 mg/dL increment per 10 units.

Blood Components Apheresis: centrifugation in a closed tubing system All major blood products can be obtained by pheresis Therapeutic pheresis: Red cell exexchange Plasmapheresis Platelet pheresis Leukapheresis Stem cell collection Blood Plasma Platelets White cells Red cells Citrate anticoagulant

Transfusion Indications, RBCs Red cell: Improve oxygen-carrying capacity Hemoglobin of 7 g/dL threshold Possible exception (higher threshold) for symptomatic cardiac patients Restrictive transfusion associated with a trend toward lower hospital mortality, and reduced number of units transfused Simple transfusion: Partial correction of blood loss One unit at a time is appropriate for most patients Exchange transfusion Reduce hemoglobin S concentration in sickle cell emergencies Stroke prophylaxis in sickle cell disease

Transfusion Indications: Platelets Platelet transfusion threshold: 10,000 20,000 fever, infection 50,000 surgery or active bleed 80-100,000 neurosurgery Platelet dysfunction: No threshold Massive transfusion: Generally more than one blood volume Average increment per platelet dose: 25,000-50,000 Contraindications: Absolute: TTP, HIT Relative: ITP

Transfusion Indications: FFP Temporary reversal of coagulopathy: Liver disease, if bleeding or prior to invasive procedures Duration of reversal few hours (shortest half-life of coagulation factor) Timing before surgery Dose: about 10 mL/kg (2-3 units in average adults) Complete reversal not necessary (INR 1.5 or below) Urgent warfarin reversal: 4 factor PCC preferred to FFP (Kcentra) Factors II, VII, IX, X, protein S, protein C Quick (15 min) Low-volume Expensive TTP: Plasma exchange, replace deficient enzyme ADAMTS13

Transfusion Indications: Cryoprecipitate Typical dose 5-10 pooled units (50-200 mL volume) Fibrinogen, von Willebrand factor, factor VIII, factor XIII Primarily used for fibrinogen replacement: 70-100 mg/dL increment per 10 units Target fibrinogen > 100 mg/dL, >150 preferable Uremic platelet dysfunction (vWF), DDAVP can be used

Massive Transfusion One or more blood volume within 24 hours: ~ 10 units Dilutional coagulopathy after 15-20 units Transfuse platelets, FFP, cryo Citrate induced hypocalcemia Perioral paresthesia, tetany Treatment: Calcium gluconate, calcium chloride Hypothermia Blood warmer

Transfusion Complications: Acute hemolytic reaction ABO mismatch Recipient IgM Anti-A and/or Anti-B lyse donor cells Intravascular hemolysis: Complement activation DIC Red urine, hemoglobinuria Renal failure Fever, chills Flank pain Hypotension Sense of impending doom As little as 10-15 mL of red cells sufficient to produce the reaction Results from patient identification error Difficult to recognize in anesthetized patients

Delayed Hemolytic Transfusion Reaction Requires prior recipient sensitization to minor blood groups: Pregnancy (fetal red cells in maternal circulation) Transfusions (multiple) Antibody level may fall below detection level with time Initial antibody screen negative Anamnestic response upon re-exposure Extravascular hemolysis and drop in HGB 1-2 weeks following transfusion and new antibody on repeat screen Typical scenario: multiparous woman transfused and improved, returns 10 days later with more severe anemia with no evidence of blood loss

Febrile Non-hemolytic Transfusion Reaction About 1% of transfusions of cellular products Fever, chills Results from WBC cytokines released during storage Reduced risk with leukoreduction No evidence to support the use of antipyretics prior to transfusion Diagnosis of exclusion, stop transfusion and rule out Infection Hemolysis TRALI

Allergic Reactions Urticaria About 2% of transfusions Antibodies or proteins in donor plasma Itching, hives Managed symptomatically Antihistamines Steroids Resume transfusion

Anaphylactic Reactions Uncommon IgA deficient recipients Respiratory distress Wheezing Hives Shock Prevention: Transfuse from IgA deficient donors Saline washed red cells

Transfusion Related Acute Lung Injury (TRALI) HLA or neutrophil antibodies in donor serum to recipient white cells More common in females donors (antibodies with pregnancy) More common with plasma transfusion Hypoxia, fever Bilateral pulmonary infiltrates Exclude other causes: Infections, heart failure Supportive management Exclude donor from future plasma donation

Alloimmune Platelet Refractoriness HLA antibodies in the recipient bind to and rapidly clear transfused platelets Poor platelet increment 10 minute to an hour post transfusion Management: HLA matched platelets Cross-matched platelets Prevention: Leukoreduction reduces the risk of developing HLA antibodies

Transfusion Associated GVHD Donor T lymphocytes in: Immunocompromised recipient Donor related to recipient Pancytopenia, rash, hepatitis, diarrhea, 1-4 weeks following transfusion Diagnosis: Chimerism study to detect donor derived lymphocytes Prognosis: Very high mortality Prevention: Irradiated blood products

Post Transfusion Purpura Recipient platelets lacking an antigen Recipient has antibodies to that antigen Antibodies destroy donor platelets in 1-2 weeks Antibodies destroy own platelets (bystander effect)

Transfusion associated circulatory overload TACO Common Volume overload picture Pulmonary edema Elevated BNP Supportive management

Infectious Complications Most common with platelets: Stored at room temperature 1/2000 HBV 1/250,000 HIV 1/1,500,000 HCV 1/1,000,000 HTLV I-II 1/1,000,000 Minute risk Babesiosis Syphilis West Nile Chagas Zika CJD Malaria Lyme

Blood Product Modifications Leukoreduction: Pre-storage filtration reduces the risk of Febrile reactions Alloimmune platelet refractoriness CMV risk (equivalent to CMV negative blood) Most blood products in the US are leukoreduced Irradiation: Deactivates lymphocytes and reduces the risk of Transfusion associated GVHD Indications: Immunocompromised host Related donors

Saline Washing Repeated washing of red cells or platelets with saline Removes plasma proteins Transfusion in IgA deficient recipients Recipients experiencing repeated severe allergic reactions

Question 1 60-year-old female admitted with hematemesis and a hemoglobin of 6.5 g/dL, she received 3 units of packed red cells and at the time of discharge her hemoglobin was 9 g/dL. 10 days after discharge she was readmitted with fatigue, a hemoglobin of 6 g/dL. Total bilirubin of 2.5 mg/dL with direct bilirubin 0.5. Stool Hemoccult was negative. What is the most appropriate next step: Transfuse 2 units of irradiated packed red cells Repeat antibody screen Upper endoscopy Start steroids Transfuse 2 units of O- blood

Answer 1 B Delayed hemolytic transfusion reaction related to anamnestic response and re-appearance of minor blood group antibody in a multiparous woman. repeat antibody screen can detect the new antibody, and compatible units lacking the corresponding antigen can be transfused. Type O blood lacking the A and B major blood groups still has the minor groups. irradiation deactivates lymphocytes and does not affect the blood groups and will not be of benefit in this setting.

Question 2 22-year-old healthy college student donating apheresis platelets for the first time. About an hour into the procedure, she is starting to feel a little anxious and restless, she is complaining of numbness around her mouth. Vitals are normal except for a heart rate of 100. What is the most appropriate next step: Stop the procedure Give a dose of lorazepam for anxiety and continue the procedure Tell her she should donate whole blood only from now on Start calcium gluconate infusion Draw blood cultures

Answer 2 D Citrate which is used as anticoagulant in blood products and for apheresis procedures binds calcium and causes hypocalcemia, this presentation is typical for a citrate reaction. The treatment is calcium replacement most often given intravenously but oral replacement can be given.

Question 3 55-year-old lady receiving chemotherapy, developed thrombocytopenia with a platelet count of 7000. 5 units of random donor platelets were ordered and about 15 minutes into the infusion she developed fever of 102.2, chills, heart rate 110 and blood pressure 95/50. She has no wheezing, dyspnea or rash. In addition to stopping the transfusion, what is the most appropriate next step? Give antihistamines, steroids, resume transfusion once she is feeling better Test the donor for HLA antibodies Draw blood cultures, start antibiotics, send the product to the blood bank for testing Give intravenous furosemide Give steroids, antihistamines, intravenous fluids, and transfuse washed blood products in the future

Answer 3 C Platelets are stored at room temperature, and platelet transfusion is associated with the highest risk of bacterial contamination. Transfusion reactions associated with hemodynamic instability include bacterial contamination, anaphylactic reactions, circulatory overload, and TRALI, all of which except bacterial contamination are associated with prominent respiratory symptoms

Question 4 40-year-old male receiving warfarin for deep vein thrombosis, hospitalized with lower gastrointestinal bleed and received 2 units of fresh frozen plasma for reversal of coagulopathy. 6 hours following the transfusion he developed dyspnea and hypoxia. Temperature 100.5. Physical examination reveals no jugular vein distention or peripheral edema. CBC is normal. Which of the following is most likely to be associated with this condition? Bilateral pulmonary infiltrates on chest x-ray Reduced LEFT ventricular systolic function on echocardiogram Female plasma donor Antibodies against HLA antigens on recipient neutrophils A, C, and D

Answer 4 E Transfusion related acute lung injury, TRALI results from donor HLA antibodies or neutrophil specific antibodies in donor plasma reacting with recipient neutrophils, causing pulmonary infiltrates in the setting of normal cardiac function. Female donors are implicated more often because of prior allo-immunization from pregnancy

Question 5 55-year-old male with alcoholic liver cirrhosis presents with pleural effusion requiring diagnostic thoracentesis. CBC shows a platelet count of 62,000, INR 1.4, PTT within the reference range. Prior to the procedure he should receive: 2 units of fresh frozen plasma to correct INR to 1.2 or below 1 platelet pack to correct the platelet count to 100,000 One unit of fresh frozen plasma and one platelet pack 10 units of cryoprecipitate Proceed with the procedure without transfusion

Answer 5 E There is no evidence that mild coagulopathy related to liver disease needs to be corrected prior to surgical interventions. platelet count greater than 50,000 is sufficient for most surgical interventions.

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