Non-Infectious Risks of Transfusion: Human Errors and Their Consequences

2. دکتر مجید وفایی فلوشیپ خون و سرطان کودکان بیمارستان شفا اهواز

3. Non-infectious Risks of Transfusion

4. If not Infectious, What are the Risks? Non-Infectious Risks • Human Error and Clerical Errors • Improper Administration of the Blood Product TRALI, 7% Delayed Reaction Acute Reaction Post-Tx Purpura GVHD Infections, 2% Mis-transfusion, 66% SHOT DATA 1996-2003

5. How common are errors? • Risk of an error occurring during transfusion of a blood component is 1:16,500 • Risk of an ABO incompatible transfusion is 1:100,000 • Risk of death as a result of an 'incorrect blood component transfused' is around 1:1,500,000

6. Clerical Errors • Sample drawn on the wrong patient • It is vital to check the name and patient ID number every time you draw a blood sample for testing • Blood is hung on the wrong patient • It is vital to check that the name and patient ID number on the unit of blood matches that on the patient’s ID band • Labeling error • Label tubes as you draw or use them rather than batch labeling. When batching, the risk of a tube switch exists • Sample tubes must be labeled at the patient’s bedside/chairside

7. Sample Collection Errors at BHC Identified by the Blood Bank

8. Where do the Errors occur? SHOT Errors, 1996-2003, n=2340 Blood Center, 1.7% Prescription, sampling, request, 19.7% Unknown, >1% Other, 1% Hospital Blood Bank, 29% Collection, Administration, 48.4% Serious Hazards of Transfusion Study in UK

9. Transfusion Errors • Transfusion errors in New York State* • Erroneous administration (1/19,000 units) • ~50% of errors occurred outside the blood bank • Blood bank errors • 29% of errors occurred in the blood bank (wrong test, issuance of wrong unit etc.) • Multiple errors • 20% involved errors at blood bank and on floor or lab • Increased scrutiny of hospital reporting by regulatory agencies * JV Linden et al (2000) Transfusion, 40: 1207

10. Administration Errors • What can be added to a line during a transfusion? • Normal saline (0.9%) • ABO compatible plasma • 5% Albumin • Plasma protein fraction • What can never be added to a line during a transfusion? • Lactated Ringer’s solution • Contains 3 mEq/L ionized calcium • 5% Dextrose • Hypotonic sodium chloride solutions • Almost all Medications Running any of the above “never solutions” along with blood risks hemolyzing the transfused cells.

11. Alloimmunization • Chronically transfused patients can develop antibodies to WBCs as well as RBCs • Antibodies to WBCs • Can cause febrile non-hemolytic transfusion reactions • May avoid or reduce frequency and severity by leukoreduction or pre-medication with antipyretics • Antibodies to RBCs • Can cause either acute (AHTR) or delayed hemolytic reactions (DHTR) • Can lead to hemolytic disease of the newborn • May affect the availability of blood

12. Alloimmunization • Incidence: • RBC Antigens: 1:100 (1%) • HLA Antigens: 1:10 (10%) • Etiology: Immune response to foreign antigens on RBC, WBCs, and platelets (HLA) • Presentation: Positive blood group antibody screening test, platelet refractoriness, delayed hemolytic reaction, hemolytic disease of the newborn

13. Impact of RBC Alloimmunization • Hemolytic Transfusion Reactions • Acute • Delayed • May make laboratory evaluation more complicated • Delay and Difficulty in providing compatible blood for transfusion • Hemolytic Disease of the Newborn

14. Recognition of Acute Transfusion Reactions • Signs and symptoms that may be associated with any type of acute transfusion reaction • Fever • 1C (2F) increase in body temperature associated with transfusion • Shaking chills (rigors) with or without fever • Pain at the infusion site or in the chest, abdomen, or flanks • BP changes • Usually acute either hypertension or hypotension

15. Immunologic Hemolytic Fever/Chill Urticarial Anaphylactic Non-Immunologic Hypotension associated with ACE inhibition TRALI Circulatory overload (TACO) Non-immune hemolysis Air embolus Hypocalcemia Hypothermia Types of Acute (<24 hours) Transfusion Reactions (TXRs)

16. Hemolytic Transfusion Reactions • Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated • Immune-mediated • Occur when a patient has an antibody directed against a RBC antigen on the transfused RBCs or when the plasma in the transfused blood product contains an antibody to an antigen on the patient’s own RBCs • Nonimmune-mediated • Occur when RBCs are damaged prior to transfusion • Generally results in hemoglobinemia and hemoglobinuria without significant clinical symptoms.

17. Acute Immune-Mediated Hemolytic Transfusion Reactions • Incidence: 1:38,000 to 1:70,000 • Some reports as high as 1:25,000 transfusions • Occur during or within 24 hours after transfusion • Can be fatal • Most often due to clerical and sample identification errors • Hemolysis can be intravascular or extravascular • Intravascular • Most often due to ABO blood group mismatch

18. Signs and Symptoms Chills Fever Hypotension Renal failure with oliguria DIC Back pain Pain along infusion vein Anxiety Pain at infusion site Hemoglobinurea Hemoglobinemia Can detect 2.5 to 5 ml RBC hemolysis Acute Immune-Mediated Hemolytic Transfusion Reactions

19. Acute Immune-Mediated Hemolytic Transfusion Reactions • Treatment • Immediately discontinue the transfusion • Maintain venous access for emergency management. • Anticipate hypotension, renal failure, and DIC. • Prophylactic measures to reduce the risk of renal failure may include • Low-dose dopamine (1-5 mcg/kg/min) • Vigorous hydration with crystalloid solutions (3000 mL/m2/24 h) • Osmotic diuresis with 20% mannitol (100 mL/m2/bolus followed by 30 mL/m2/h for 12 h). • If DIC is documented and bleeding requires treatment, transfusions of frozen plasma, pooled cryoprecipitate for fibrinogen, and/or platelets may be indicated.

20. Febrile Non-Hemolytic Transfusion Reactions (FNHTRs) • Most frequently reported of all reactions • About 1% of all transfusions • Incidence: • RBCs: 1:200 to 1:17 (0.5-0.6%) • Platelets: 1:100 to 1:3 (1-38%) • Increase in temperature of 1C or 2F with no other explanation • Presentation: Chills/rigors, rise in temperature (>1C), headache, vomiting • Most FNHTRs can be prevented

21. Febrile Non-Hemolytic Transfusion Reactions (FNHTRs) • Etiology: Due to antibodies to WBCs and/or accumulated cytokines especially in platelets • Current theory is that FNHTRs are caused by cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha (TNFa), which are generated and accumulate during the storage of blood components • Prevention: • Antipyretic pre-medication with acetaminophen • Leukoreduced blood products

22. Urticarial TXRs • Incidence: 1:100 to 1:33 (1-3%) • Second most frequently reported reaction • Presentation: Urticaria, pruritis, rash, flushing • Etiology: Antibody to donor plasma proteins • Due to Type 1 hypersensitivity to donor plasma proteins • Urticarial transfusion reactions (UTRs) occur when soluble allergenic substances in the plasma of the donated blood product react with preexisting IgE antibodies in the recipient. This causes mast cells and basophils to release histamine, leading to hives or urticaria

23. Urticarial TXRs • Lab Testing: Rule out hemolysis • Prevention: • Antihistamines, treatment or pre-medication (PO or IV) • May restart transfusion of unit slowly after antihistamine if symptoms resolve

24. Anaphylactic TXRs • Incidence: 1:20,000 to 1:50,000 • 1:800 to 1:900 people have no detectable IgA • Etiology: Antibody to donor plasma proteins (includes IgA, C4) • Presentation: Hypotensionwithout fever, urticaria, bronchospasm (respiratory distress, wheezing), local edema, anxiety

25. Treatment: Immediate cessation of the transfusion Epinephrine, 0.3 mL of a 1:1000 solution intramuscularly Preparation, for possible administration, of an intravenous epinephrine drip Airway maintenance, oxygenation Volume maintenance with saline Vasopressors (eg, dopamine), if necessary Prevention: Antihistamines, corticosteroids, beta-2 agonists IgA-deficient blood components if IgA-deficient patient Washed blood products Anaphylactic TXRs

26. Transfusion Associated Acute Lung Injury (TRALI) • Incidence: 1:1,300 to 1:5,000 • Etiology: Most likely caused by antibodies in donated blood products that react with patient white cells or visa-versa • Antigen-Antibody reaction results in increasing the permeability of the pulmonary micro-circulation so that high-protein fluid enters the interstitium and the alveolar air spaces • Presentation: Noncardiogenic pulmonary edema, hypoxemia, respiratory failure, hypotension, fever, dypsnea, chills • Develops within 1-2 hours of transfusion. Usually present within 4-6 hours • Can be difficult to distinguish from ARDS

27. TRALI • Leading cause of transfusion deaths in US for the last two reporting years • Pulmonary edema arises from capillary injury not volume overload • Can occur after the transfusion of any type of blood product • Most patients (>80%) recover adequate pulmonary function within 2 to 4 days • Observed mortality rate is less than 10% • Patients are treated with supportive care and may require ventalitory assistance • Diuretics are contraindicated Normal Chest X-Ray TRALI Chest X-Ray

28. TRALI Edema Fluid

29. Transfusion Associated Circulatory Overload (TACO) • Incidence: <1% • Mayo Clinic estimated that incidence to be 1:708 • Etiology: Volume overload Pulmonary edema secondary to congestive failure can occur with transfusion-associated volume/circulatory overload (TACO) • At risk patients include elderly patients, small children, and/or those with compromised cardiac function. • This often occurs in association with surgery, where large fluid volumes and some blood are administered. • Presentation: Dyspnea, orthopnea, tachycardia and a wide pulse pressure, often with hypertension, and may begin near the end of the transfusion, or within six hours. Headache is common, and seizures have been reported.

30. Transfusion Associated Circulatory Overload (TACO) • In order to avoid TACO for routine transfusions of blood components, a transfusion rate of approximately 2.0 to 2.5 mL/kg per hour is acceptable. • Thus, for an average-sized adult, one unit of packed red cells should be transfused over a 1.5 to 2 hour period. • Patients deemed to be at risk of TACO (eg, small stature or low body weight, elderly, known or suspected poor cardiac function) can generally be safely transfused at a rate of 1 mL/kg per hour. • Such patients should also be monitored more closely during the transfusion for signs and symptoms of TACO.

31. Transfusion Associated Circulatory Overload (TACO) • Treatment consists of fluid mobilization (diuretics) and supplementary oxygen. • Noninvasive positive pressure ventilation may be helpful in the acute management of patients with severe respiratory compromise. • Phlebotomy in 250 mL increments, with or without reinfusion of the removed red cells, may be necessary if symptoms persist or diuresis cannot be promoted.

32. Hypothermia Incidence: Dependent on clinical setting Etiology: Rapid infusion of cold blood Presentation: Cardiac arrhythmia Therapeutic/ Prophylactic approach: Employ blood warmers Non-Immune Hemolysis Incidence: Rare Etiology: Physical or chemical destruction of blood (heating, freezing, hemolytic drug or solution added to blood or line) Presentation: Hemoglobinuria Lab testing: Plasma-free Hb DAT (should be negative) Test unit for hemolysis Look at segments verses unit Therapeutic/Prophylactic approach: Identify and eliminate cause Other Rare Complications

33. Air Embolus Incidence: Rare Etiology: Air infusion via line Presentation: Sudden SOB, acute cyanosis, pain, cough, hypotension, cardiac arrhythmia Therapeutic approach: Lay patient on left side with legs elevated above chest and head Hypocalcemia (Ionized Ca2+) Incidence: Dependent on clinical setting Etiology: Rapid citrate infusion. Can occur with massive transfusion of citrated blood, delayed metabolism of citrate, or during apheresis procedures Presentation: Paresthesia, tetany, arrhythmia Other Rare Complications

34. Immunologic Alloimmunization RBC antigens HLA antigens WBC antigens Hemolytic Graft-vs-Host Disease (TA-GVHD) Post-transfusion Purpura Non-Immunologic Iron overload Delayed (>24 hours) TXRs

35. Delayed Hemolytic TXRs • Incidence: 1:11,000 to 1:5000 • Etiology: Anamnestic immune response to RBC antigens • Occur 5-20 days after transfusion • Hemolysis: • Classically extravascular • Can be intravascular • Kidd antibodies are able to fix complement and thus can cause intravascular hemolysis

36. Delayed Hemolytic TXRs • Caused by antibodies that were undetectable at the time of compatibility testing • Patients frequently “shop around” for their health care and are thus treated at different hospitals • Without an accurate transfusion history &/or prior test results it is possible to miss clinically significant antibodies • >30% of antibodies disappear (become undetectable) with time, but recipients can mount an anamnestic response to further stimulation by transfusion

37. Delayed Hemolytic TXRs • Presentation: Fever, decreasing hemoglobin, new positive antibody screening test, mild jaundice, often no signs or symptoms • Lab testing: • Positive antibody screen • Spherocytes on peripheral screen • DAT (Classically “mixed field”) • Test for hemolysis (visual inspection for hemoglobinemia, LDH, bilirubin, urinary hemosiderin as clinically indicated)

38. Delayed Hemolytic TXRs • Prevention: Excellent patient histories and historical blood bank/blood center testing records • Enables the correct RBCs lacking the patient’s antibody to be selected

39. Delayed Hemolytic TXRs • 50% of patients who become alloimmunized will develop multiple antibodies • 50% are anti-Rh blood group system • E most common • 20% are anti-Kell and anti-Kidd (Jka & Jkb)

40. Hemolytic Disease of the Newborn • Maternal IgG antibodies made following a previous RBC exposure cross the placenta • IgG antibodies bind to the fetal RBCs • The antigen-antibody complexes result in fetal RBC hemolysis and anemia

41. Hemolytic Disease of the Newborn • Prolonged anemia leads to increased erythropoiesis in fetal liver • This causes disruption of portal circulation, impaired albumin synthesis, decreased plasma colloid osmotic pressure • The decreased osmotic pressure of severe anemia causes cardiovascular failure, tissue hypoxia, and death in utero

42. Transfusion Associated Graft-vs-Host Disease (TA-GVHD) • Incidence: Rare • Etiology: Donor lymphocytes engraft in recipient and mount an attack on the host tissues • Presentation: Rash, erythroderma, maculopapular rash, anorexia, nausea, vomiting, diarrhea, hepatitis, pancytopenia, fever, bone marrow fibrosis and failure • Lab testing: • Skin biopsy • Bone marrow biopsy and HLA typing

43. TA-GVHD • Can develop in patients whose immune system fails to recognize transfused WBC as foreign • Transfused WBCs (CD4 & CD8 cells) attack and kill host’s immune system • Prevention: Irradiation of blood components for patients at risk of developing TA-GVHD • Including: • Low infant birth weight neonates • Congenital immunodeficiencies • Certain malignancies including Hodgkin’s Disease • Fludarabine chemotherapy • Hematopoietic stem cell transplants • HLA matched products • Blood products from blood related donors

44. Irradiation of Blood Products • Since TA-GVHD depends upon: • Number of viable, immunologically competent lymphocytes transfused • Degree of HLA similarity between donor and recipient • Immunocompetence of recipient • Gamma irradiation reduces/eliminates lymphocyte proliferative capacity (2500cGy) • It is necessary to irradiate all cellular blood components including RBC, platelets, and granulocytes

45. Post-Transfusion Purpura (PTP) • Incidence: Rare (>250 cases in literature) • Female-to-male ratio is 26:1 • Etiology: Recipient platelet antibodies destroys autologous and transfused platelets • Presentation: Thrombocytopenic purpura, bleeding, 8-10 days following transfusion • The typical patient is a multiparous woman or a patient with history of previous transfusions • Thrombocytopenia is usually severe with platelet counts below 10,000 • Can be associated with significant hemorrhage

46. Post-Transfusion Purpura • Treatment • Consists of prompt initiation of IVIG at a dose of 2 g/kg over 2 or 5 days, in split fractions • Steroids can be used in conjunction • Plasma exchange (TPE) • Transfusion of HPA-1a negative platelets (if patient is HPA-1b) can be used in life threatening hemorrhagic circumstances • Course • PTP is generally self-limited with full recovery within 21 days • 10-15% of patients have been reported to die from PTP

47. Iron Overload • Major problem for chronically transfused patients • Sickle Cell Anemia • Thalassemia • Incidence: Invariable after >100 units of RBCs, risk occurs after >50 units • Etiology: Multiple transfusions with obligate iron load in transfusion-dependent patient • 1 mg of iron per 1 ml of RBCs transfused (every unit of RBC contains approximately 200mg iron) • Presentation: Diabetes, cirrhosis, cardiomyopathy

48. THE BEST TX IS NO TRANSFUSION