Unit 12 Adverse Complications of Blood Transfusion

1. Unit 12 Adverse Complications of Blood Transfusion Terry Kotrla, MS, MT(ASCP)BB

2. Introduction • Transfusion of blood and blood components safe and effective way to correct hematologic deficits. • Complications during transfusion may occur, called “transfusion reactions” and include broad range of events and problems. • Some reactions preventable, some are not. • Risk of transfusion must be weighed against benefits. • Two categories: • Acute or immediate reactions • Delayed reactions

3. Clinical Evaluation of Transfusion Reaction • Time between reaction and investigation must be as short as possible. • Two pronged evaluation • Clinical evaluation of patient • Laboratory investigation and testing • Responsibility of initiation rests with transfusionist.

4. Procedure for Transfusion • Blood product picked up from transfusion service. • Two licensed personnel check forms against blood product label and patient armband. • Take vital signs. • Start transfusion. • If possible stay with patient first 15 minutes. • Retake vital signs to ensure no change. • If the same continue transfusion which must be completed within 4 hours, shorter time is preferable, usually 2 hours. • Check on patient periodically. • Take vital signs upon completion of transfusion

5. What to Watch for During Transfusion • Fever • Chills • Abdominal, chest, flank or back pain • Hyper- or hypotension • Nausea/vomiting • Skin manifestations: urticaria, rash, flushing, pruritus and localized edema. • Respiratory distress: wheezing, coughing and dyspnea • Jaundice or hemoglobinuria • Abnormal bleeding or generalized bleeding (DIC) • Oliguria or anuria • Pain or burning at infusion site. • Shock

6. Actions for Complications • Any sign or symptom must be considered potentially life-threatening. • Fever and chills may simply be a benign reaction or an indication of acute hemolysis. • Two areas of action for the transfusionist: • Patient focused steps • Component focused steps

7. Patient Focused Steps • Stop the transfusion immediately to limit the amount of blood infused and notify a responsible physician. • Keep the IV line open with infusion of normal saline. • At the patient's bedside perform clerical recheck between the patient and component: check all labels, forms and patient identification to determine if the patient received the intended component. • Notify patient’s physician immediately.

8. Component Focused Steps • Contact transfusion service immediately. • Return discontinued bag of blood, the administration set without the IV needle, attached IV solutions and all the related forms and labels. • Send required blood samples, carefully drawn to avoid mechanical hemolysis, to the transfusion service as soon as possible. • Send other blood samples for evaluation of acute hemolysis as directed by the transfusion service director or patient's physician.

9. Laboratory Investigation • Handle STAT each and EVERY time!! • Clerical check identification of patient blood sample, labels, paperwork and donor blood. • Repeat ABO testing on the post-transfusion sample. • Visual check comparing the patient's pretransfusion and post-transfusion specimen for color of serum or plasma. • Perform a DAT on the post-transfusion specimen. • If all are negative or normal, nothing further needs to be done.

10. Additional Laboratory Tests for AHTR • If DAT positive or hemolysis present in post-transfusion sample additional testing must be performed. • Repeat ABO/D on patient pre- and post-transfusion samples as well as donor. • Repeat antibody screen on pre- and post-transfusion samples. • Repeat crossmatch on pre- and post-transfusion samples THROUGH AHG. • If tests on pre-transfusion sample do not match post-transfusion sample notify blood bank supervisor or medical director AND patient’s physician.

11. Investigation for Non-Immune Hemolysis • Consider bacterial contamination of the donor unit if: • The cells or plasma have brownish or purple discoloration. • There are clots or abnormal masses in the liquid blood or segments closest to primary bag appear hemolyzed. • The plasma is opaque or muddy. • There is a peculiar odor. • If any of these are notated set up cultures at 4 C, 20-24 C and 35-37 C and perform a gram stain on the unit.

12. Investigation for Non-Immune Hemolysis • Examine the supernatant plasma from the donor blood container for presence of free hemoglobin. • Examine the blood remaining in the administration tubing for presence of free hemoglobin. • Consider the possibility that the patient or donor has an intrinsic RBC defect such as G-6-PD deficiency or PNH. • Consider the possibility of mechanical hemolysis. • Consider osmotic hemolysis due to inadvertent entry into the circulation of hypotonic fluids

13. Laboratory Evaluation – Hemolysis Proven • Examine post-transfusion urine specimens for the presence of free hemoglobin. • Test post-transfusion serum samples for unconjugated bilirubin, carefully recording the timing of sample collection. Peak levels occur at 5-7 hours and disappear within 24 hours. • Measure serum haptoglobin in pre- and post-transfusion specimens.

14. Hemolysis Suspected But Tests Uninformative • Perform antibody detection tests with more sensitive methods. • Perform DAT and IAT daily or more frequently. • Measure H&H at frequent intervals to document rise or decrease. • Type cells of recipient and donor to find antigens present on donor but absent on recipient. • If hemoglobinopathy present perform hemoglobin electrophoresis to verify presence of normal hemoglobin.

15. Acute Hemolytic Transfusion Reaction • Triggered by antigen-antibody reaction which activates complement, coagulation systems and endocrine response. • Catastrophic clinical events may occur • Shock • DIC • Acute renal failre • Life threatening AHTRs almost always due to ABO mismatch. • Other blood group incompatibilities may cause hemolysis usually not as severe as ABO.

16. Acute Hemolytic Transfusion Reaction • Diagnosis • Most common initial sign is FEVER. • Reaction may occur with as little as 10-15 mL of incompatible blood. • Onset symptoms may be mild: vague uneasiness, abdominal, chest, flank or back pain. • First sign patient observes is red or dark urine with or without back pain. • Severity directly related to amount of blood transfused. • Anesthetized bleeding at surgical site, hypotension or presence of hemoglobinuria. • STOP TRANSFUSION, keep IV line open.

17. Therapy for AHTR • Goal to treat hypotension and promote renal blood flow. • Hemoglobin toxic to kidneys, give fluids to maintain urine output, diuretics to promote urine formation. • DIC may occur. • Consult with appropriate medical specialist to ensure appropriate treatment.

18. Prevention of AHTRs • Impossible • Hemolysis may occur even if crossmatch compatible – anamnestic response. • Human error • Wrong sample from wrong patient. • Tech mixed up samples. • Blood transfused to wrong patient. • SOPs MUST BE FOLLOWED BY EVERYONE. • Fatalities must be reported to FDA within 24 hours.

19. Other Immediate Complications • Febrile non-hemolytic • Transfusion related sepsis • Allergic reactions • Transfusion associated circulatory overload (TACO) • Transfusion related acute lung injury (TRALI) • Massive transfusion

20. Febrile non-hemolytic • Rise in temperature of 1C or 2F in association with transfusion and no other identifiable cause. • Caused by antibodies to transfused lymphs, grans or platelets. • Usually occur in repeatedly transfused or pregnant patients. • Usually benign BUT may be first sign of AHTR. • STOP TRANSFUSION and initiate work up • Prevention – pre-storage leukoreduction has decreased incident. • Pre-medicate with antipyretics NOT aspirin.

21. Transfusion Related Sepsis • Signs/symptoms which occur during or shortly after transfusion. • Fever, particularly 101F • Shaking chills • Hypotension • STOP TRANSFUSION IMMEDIATELY – START WORK UP • May progress to shock, hemoglobinuria, DIC and renal failure. • Platelets most frequently implicated • Life threatening sepsis due to platelet transfusion 1 in 100,000 • Immediate fatal outcome due to platelet transfusion 1 in 500,000

22. Transfusion Related Sepsis • Bacteria may enter component containers or contaminate port of bag during • donor phlebotomy or • component preparation. • Most common infectious hazard of transfusion.

23. Transfusion Related Sepsis • Components from same donation may be contaminated. • Platelets most commonly implicated.

24. Transfusion Related Sepsis • Each unit must be inspected prior to issue. • Quarantine if: • Purple color, • clots in bag • hemolysis, especially sprigs closest to primary bag.

25. Allergic Reactions • Urticaria • Commonly encountered • Characterized by local erythema, hives and itching, usually without fever or other complications. • If localized urticaria is the only manifestation, it is usually not necessary to discontinue the transfusion. • Etiology unknown • Pre-treat with antihistamines.

26. Allergic Reactions • Anaphylactic Shock • Occurs after the infusion of only a few milliliters of blood or plasma and the absence of fever. • Onset characterized by: coughing, broncho spasm, respiratory distress, vascular instability, nausea, abdominal cramps, vomiting, diarrhea, shock and loss of consciousness. • Reactions may occur in IgA deficient patients who have developed anti-IgA antibodies after immunization by previous transfusion or pregnancy. • STOP TRANSFUSION IMMEDIATELY–START WORK UP • Sensitized IgA-deficient patients must be transfused with blood and blood components that lack IgA.

27. Transfusion Associated Circulatory Overload (TACO) • Hypervolemia must be considered if dyspnea, severe headache, peripheral edema or other signs of congestive heart failure occur during or soon after transfusion. • Rapid increases in blood volume poorly tolerated by patients with compromised cardiac or pulmonary status. • Symptoms: coughing, cyanosis, orthopnea, difficulty breathing. • STOP TRANSFUSION IMMEDIATELY–START WORK UP • For susceptible patients give small volumes SLOWLY.

28. Transfusion Related Acute Lung Injury (TRALI) • Number 1 cause of transfusion related deaths. • Chest x-ray acute pulmonary edema, acute respiratory insufficiency but no evidence of heart failure. • Symptoms of RDS after infusion of volumes to small to produce hypervolemia. • May be accompanied by chills, fever, cyanosis and hypotension. • Occurs within 6 hours of transfusion, most within 1-2 hours after transfusion. • One study 100% of patients require O2, 72% of those require mechanical ventilation as well.

29. Transfusion Related Acute Lung Injury (TRALI) • All plasma products have been implicated. • Reaction between DONOR leukocyte antibodies and recipient as well as biologically active lipids. • WBCs aggregate, trapped in lungs, release cytokines which damage and cause fluid to enter alveoli spaces. • STOP TRANSFUSION IMMEDIATELY–START WORK UP • Treatment IV steroids and respiratory support. • PREVENTION: Do not make plasma products from female donors.

30. Complications of Massive Transfusion • Citrate toxicity • Hemostatic abnormalities • Hyperkalemia • Hypocalcemia • Air embolism • Hypothermia

31. Transfusion-Related Fatalities by Complication, FY2005 through FY2009

32. Delayed Hemolytic Transfusion Reaction (DTR) • Two types • Due to primary response • Due to secondary response

33. DTR Primary Immune Response • This is the immunizing event, takes weeks to months. • As antibody titer increases in titer and avidity reacts with antigen positive donor cells present. • Degree of hemolysis depends on • Quantity of antibody present • Quantity of antigen positive donor cells present. • Usually unsuspected clinically but may suspect based on: • Unexplained fall in hemoglobin • Positive DAT • Appearance of new alloantibody

34. DTR Secondary Immune Response • Previously immunized individual. • Alloantibodies may fall to undetectable levels. • Kidd antibodies most common. • Pre-transfusion testing reveals no unexpected antibodies. • Within 3-7 days after transfusion anamnestic response • Large number of antigen positive red cells present. • Rapid increase in antibody titer • Symptoms: fever, unexplained fall in hemoglobin, jaundice. • RARELY hemoglobinuria and renal failure.

35. Detection of DTR • Transfusion service may diagnose if another crossmatch is ordered. • Current sample may have positive DAT. • Perform elution • Identify antibody • Antibody screen • May be negative, all antibody produced going onto donor rbcs • Will become positive once all donor antigens coated. • Reason that sample for compatibility testing be no more than 3 days old at time of testing. • ALWAYS CHECK PATIENT HISTORY - Once immune antibody identified must ALWAYS give antigen negative blood even if antibody screen is negative.

36. DTR

37. Infectious Complications • Viral hepatitis • Cytomegalovirus • Malaria • Babesiosis • Syphilis • Chaga’s Disease • Toxoplasmosis • West Nile Virus • Human Immunodeficiency Virus • Many more….

38. Hepatitis • Transmission of Hepatitis A rare – fecal-oral route of transmission. • All donors screened for Hepatitis B and C but transmission does occur – not through “window”. • Defer donor if only unit given patient contracted hepatitis. • Defer donor if implicated in two cases. • Identified by “look back” • Still have non-A, B, C hepatitis transmission

39. Infectious Disease Transmission • Cytomegalovirus (CMV) • Immunoincompetent/immunosuppressed. • Transmitted by leukocytes. • All blood pre-storage leukoreduced. • Malaria – no screening test available. • Very rare but cases are rising. • Travel and immigration. • Exclude donors at high risk. • Report cases to transfusion service or blood provider

40. Infectious Disease Transmission • Babesiosis • Caused by Babesia species transmitted by ticks. • Organism multiplies in RBCs. • Donors permanently deferred. • Syphilis • Caused by Treponema pallidum • Donor must be drawn during brief period of spirochetemia. • Treponemes can only survive 72 hours at 4C. • Serological test for syphilis (STS) negative in primary syphilis. • Positive STS indicates high risk life style activities.

41. Infectious Disease Transmission • Chagas’ Disease • Trypanosoma cruzi transmitted by reduviid bug. • Disease primarily found in Central & south America. • Few cases reported in Texas and California. • Cause of 30% of adult deaths in brazil. • Toxoplasmosis • Toxoplasma gondii • Unusual complication in immunosuppressed • Lyme’s disease • Borrelia burgdorferi transmitted by tick bite. • May be potential problem, no cases reported.

42. Infectious Disease Transmission • West Nile Virus • Primary reservoir birds, spread by mosquitos. • First documented transfusion cases 2002, 23 cases. • NAT test used to screen donors. • Three month deferral after illness. • Humon Immunodeficiency Virus • Attempts to prevent transmission rely on careful donor screening and sensitive tests. • No cure • Transfusions should never be given unless medically necessary.

43. Other Delayed Adverse Affects • Transfusion Associated Graft versus Host Disease (TA-GVHD) • Rare but usually fatal disease in immunosuppressed. • Donor lymphocytes engraft in recipient, consider recipient “foreign”, mount immune response. • Pretransfusion irradiation to prevent disease for • Intrauterine transfusions • Patients identified as being at risk for TA-GVHD • Cellular components donated from relatives. • Transfusion of HLA selected products.

44. Other Delayed Adverse Affects • Post-Transfusion Purpura • Rare event occurring almost exclusively in multi-parous women. • Precipitous fall in platelet count with purpura about 1 week after transfusion. • Some caused by anti-HPA-1a • Antigen has 98.3% prevalence, only 1.7% at risk. • Antibody destroys not only transfused HPA-1a positive platelets but patients own HPA-1a negative platelets. • Thrombocytopenia severe, platelet transfusions no help. • Self-limiting. • Exchange plasmapheresis for treatment.

45. Adverse Complications of Transfusions

46. End of Unit 12