transfusion reactions during and after transfusion

transfusion reactions

1. TRANSFUSION REACTIONS

2. A transfusion-related adverse reaction is a response or effect in a patient associated with the administration of blood or blood components. (Centers for Disease Control and Prevention [CDC], 2021) Acute transfusion reactions present as  adverse signs or symptoms during or within 24 hours of a blood transfusion . Delayed hemolytic transfusion reaction (DHTR) is a delayed reaction, that  occurs days to weeks following a transfusion. Definition

3. Types of Transfusion Reactions

4. Acute Hemolytic transfusion reaction Immune Non hemolytic transfusion reactions : Febrile non-hemolytic transfusion reaction Allergic transfusion reactions Anaphylactic Transfusion -associated circulatory overload (TACO) Transfusion-related acute lung injury (TRALI) Delayed Hemolytic transfusion reaction Allergic reactions Types of Transfusion Reactions We will focus on the following types:

5. Immunologic destruction of transfused red cells. Due to incompatibility of antigen on the transfused cells with antibody in the recipient’s circulation. The most common cause of severe, acute hemolytic reactions is transfusion of ABO-incompatible blood , resulting from identification errors occurring at some point(s) in the transfusion process. fatality rate 10%) Recipient’s performed antibodies attack the transfused blood Acute Immune Hemolytic transfusion reactions

6. • Failure to identify the patient with the donor unit at the time of administration. The Most Common Cause of Acute Immune Intravascular Hemolysis

7. Any time within the 24 hrs = > the time that need the plasma cells to develop antibody Can begin DURING the transfusion due to the presence of pre-formed antibodies Or Acute Hemolytic transfusion reactions

8. Hemolysis : Clinical features Fever, Flank pain, Red or brown urine Low back pain/ Flank pain Chills/ fever Thoracic constriction Tachycardia Tachypnea (rapid and shallow breathing) Vascular Collapse Bleeding Symptoms Acute Hemolytic transfusion reactions

9. Acute hemolysis result in hemoglobin release in the blood Hemoglobin breaks up into heme and Globin Heme can be then converted into bilurubin Leading to hyperbilirubinemia (high bilirubin in the blood)=> jaundice=> excess bilirubin deposit in the skin and eyes, causing them to turn yellow Symptoms Acute Hemolytic transfusion reactions Red or brown urine??

10. Bilirubin can reach the kidney and results in hemoglobinuria (red urine)=> causing Flank pain ( affects the area on either side of the lower back, between the pelvis and the ribs ) Symptoms Acute Hemolytic transfusion reactions This bilirubin is toxic and may result in kidney failure Hemolysis : Clinical features

11. Failure to maintain hemoglobin level High bilirubin level Elevated LDH Renal insufficiency Hemoglobinemia (excess of hemoglobin in the blood plasma) Hemolysis : lab features

12. Hemoglobinuria (If the level of hemoglobin in the blood rises too high, then hemoglobin begins to appear in the urine) Increased urine urobilinogen (colorless by-product of bilirubin reduction) Mildy high LFTs (Liver function tests) Hemolysis : lab features

13. • Febrile non hemolytic reactions • Allergic reactions • Anaphylaxis • TRALI (transfusion related acute lung injury) Immune Non hemolytic transfusion reactions

14. Doesn’t cause RBC destruction Occur more frequently in patients previously alloimmunized by transfusion or pregnancy. Defined to be a rise in temperature of 1◦ degree C or more and >= 38 ◦ C (heightened immune response) May accompany about 1% of transfusions. No routinely available pre- or post transfusion tests are helpful in predicting or preventing these reactions. Febrile non-hemolytic reactions

15. This occurs due to release of inflammatory mediators like cytokines from WBCs in donor blood Mechanism of Febrile non-hemolytic reactions WBCs in donor blood Cytokines

16. Another proposed mechanism of Febrile non-hemolytic reactions involves type II hypersensitivity reaction: Antibodies in recipient’s blood target HLAs on the surface of the donor’s WBCs => break and release of cytokines The released cytokines put the body in heightened immune response (symptoms similar to cold) Mechanism of Febrile non-hemolytic reactions Type II hypersensitivity reaction

17. Prevention of Febrile non-hemolytic reactions Can be prevented by the process of leukoreduction Leukoreduction involves the removal of WBCs from cellular components to reduce the risk of HLA alloimmunization , CMV transmission, and febrile nonhemolytic transfusion reactions.

18. WBCs are removed from blood before the transfusion process Patients who experience repeated, severe febrile reactions may benefit from receiving leuko -depleted components. Prevention of Febrile non-hemolytic reactions

19. Symptoms of Febrile non-hemolytic reactions Start shortly after a transfusion (60-90 mins) to 6 hours (with no other explanation). Includes: Fever Chills Headache Flushing

20. • Allergic reactions usually occur as urticaria : is  a raised, itchy rash that appears on the skin . It may appear on one part of the body or be spread across large areas. The rash is usually very itchy and ranges in size from a few millimetres to the size of a hand. Wheezing Allergic transfusion reactions No laboratory procedures are available to predict or prevent these reactions. Usually respond to antihistamines or, in severe cases, corticosteroids or epinephrine.

21. Allergic transfusion reactions < 1 hour after initiation of Transfusion Simultaneous fever is common Plasma > packed red cells  (PRC) Causes: Allergens (donor plasma) or less often to antibodies from an allergic donor .

22. A rare but dangerous complication requiring immediate treatment with: Corticosteroids ( mainly used to reduce inflammation and suppress the immune system ) and Epinephrine ( Epinephrine injection is used for emergency treatment of severe allergic reactions including anaphylaxis ) . Anaphylaxis

23. The majority of these reactions have been reported in IgA- deficient patients IgA is found in mucous membranes, especially in the respiratory and digestive tracts. It is also found in saliva, tears, and breastmilk. IgA- deficient individuals have IgA-antibodies of the IgE class.  Anti - IgA  are specific IgG antibodies against immunoglobulin A. Anti-IgA antibodies are  class-specific antibodies that can cause anaphylactic reactions to transfusions that contain plasma Patients with anti-IgA antibodies are at risk to develop an anaphylactic reaction . Anaphylactic/ Allergic Transfusion reaction ! Common in individuals with IgA deficiency

24. Most anaphylactic reactions are associated with platelets or plasma. It is caused by complement, mast cell, and basophil activation in response to a specific antigen/allergen. Patients who have anaphylactic reactions to blood products may require washed products in the future. => Prevention : Remove all the plasma from the component & transfuse IgA deficient blood components. Anaphylaxis (anti-IgA Ab)

25. Common in IgA deficiency because they have anti-IgA antibody and IgA is found in most of the blood products Individuals with IgA deficiency should receive washed blood product (IgA have been removed) Anaphylactic/ Allergic Transfusion reaction IgA have been removed

26. Anaphylactic/ Allergic Transfusion reaction Within seconds or minutes (up to 4 hours) the patient develop symptoms: Anaphylactoid reactions, characterized by: Severe dyspnea, without fever Wheezing or a whistling sound in the chest bronchospasm and/or laryngospasm. Pulmonary and/or laryngeal edema ( Abnormal accumulation of fluid in tissues of any part of the lungs/larynx, commonly associated with laryngeal injuries and allergic reactions )

27. Urticaria - type of rash Pruritus or itching Hypotension or low blood pressure which could potentially progress into respiratory arrest as well as anaphylactic shock (when blood pressure is too low to maintain adequate perfusion) respiratory arrest anaphylactic shock Urticaria Pruritus Wheezing Hypotension Anaphylactic/ Allergic Transfusion reaction

28. Transfusion-related acute lung injury (TRALI) First recognized in 1926 and was previously known as “pulmonary hypersensitivity reaction” and “non cardiogenic pulmonary edema” . Occurs when acutely increased permeability of the pulmonary microcirculation causes massive leakage of fluids and protein into the alveolar spaces and interstitium . Acute respiratory distress syndrome ARDS usually within 6 hours of transfusion. Can start within minutes to 6 hours after blood transfusion

29. Transfusion-related acute lung injury (TRALI) The underline mechanism of TARLI can be explained by two hits model. The first hit occurs before the transfusion process when any stressor like sepsis, trauma … cause neutrophil in the blood to be recruited and sequestered in the pulmonary capillaries

30. The second hit is the transfusion itself where antibodies in donor’s blood activate the neutrophils sequestered in the in the pulmonary capillaries Neutrophils respond by releasing inflammatory mediators This in turn increases pulmonary capillary permeability leading to fluid accumulation in the lung => Fluid overload => non cardiogenic pulmonary edema Transfusion-related acute lung injury (TRALI)

31. Two hits model Transfusion-related acute lung injury (TRALI)

32. Treatment consists of aggressive respiratory support Acute respiratory distress syndrome  (ARDS) occurs when fluid builds up in the tiny, elastic air sacs (alveoli) in the lungs. The fluid does not allow the lungs to be filled with enough air, which means less oxygen reaches the bloodstream. This deprives the organs of the oxygen they need to function Transfusion-related acute lung injury (TRALI)

33. Symptoms start within 6 hours: The most common signs and symptoms include:   fever, chills, urticaria , and itching . Some symptoms resolve with little or no treatment. However, respiratory distress, high fever, hypotension (low blood pressure), and red urine (hemoglobinuria) can indicate a more serious reaction. Transfusion-related acute lung injury (TRALI)

34. Delayed transfusion reactions

35. Delayed hemolytic transfusion reaction (DHTR) is a delayed reaction, that  occurs days to weeks following a transfusion, characterized by mild anemia and/or hyperbilirubinemia Hemolysis starts after 24 hours: generally within 1-2 weeks Caused by  an anamnestic antibody response in the recipient precipitated by re-exposure to a non-ABO red cell antigen previously introduced by transfusion, transplantation or pregnancy . Delayed hemolytic transfusion reaction (DHTR) Anamnestic  reaction is renewed rapid production of an  antibody  following second or later contact with the provoking antigen

36. Common Abs: Kidd System Jka Duffy System Fya Kell System K Rh System D, E, C Uncommon Abs: ABO System A1 P System P1 Delayed hemolytic transfusion reaction (DHTR)

37. It is caused by  alloimmunization against platelet antigens , anti-HPA-1a being the most frequent antibody. PTP is a rare syndrome characterized by the development of: Dramatic, sudden, and self-limiting thrombocytopenia , typically 7-10 days after a blood transfusion => Delayed Purpura is  purple-colored spots and patches that occur on the skin, and in mucus membranes, including the lining of the mouth . In a patient with a history of sensitization by either pregnancy or transfusion. Posttransfusion purpura (PTP) S elf-limiting any disease whose natural history is to resolve without treatment Thrombocytopenia is  a condition that occurs when the platelet count in your blood is too low . 

38. • Graft-vs-host disease (GVHD) is a rare (Incidence1/400,00) but extremely dangerous condition (Mortality > 90%). • GVHD normally happens to immunodeficient recipients whose immune system is unable to recognize the transfused T lymphocytes as foreign => These lymphocytes engraft in the recipient and react against the host. • It can follow transfusion of any component (4-30 days post- transfusion) that contains even very small numbers of viable T lymphocytes. Transfusion associated GVHD

39. • Severely immunocompromised recipients are at greatest risk :   Recipients of transplanted marrow or peripheral blood progenitor cells (allogenic and autologous), Selected patients with severe immunodeficiency conditions , Patients with hematologic malignancies (leukemia, lymphoma), Patients with solid tumors under chemotherapy , Recipients of blood transfusions from HLA-matched donors, or directed blood products from first-degree relatives=> This is most likely to occur when the transfused component is from a blood relative or has been selected for HLA compatibility. Transfusion associated Graft-Versus-Host Disease (GVHD)

40. GVHD remains a risk with leukocyte-reduced components because they contain sufficient residual T lymphocytes. Irradiation of the component renders T lymphocytes incapable of proliferation and is presently the only approved means to prevent GVHD. Irradiation of thawed plasma and cryoprecipitate are not necessary as they have never been associated with TA-GVHD. Fresh liquid plasma may have a small amount of viable lymphocytes and should be irradiated if the patient has indications for irradiated cellular blood products. Transfusion associated GVHD

41. TACO (transfusion associated circulatory overload) Hypothermia (Blood not warmed before transfusion - extra blanket used) Metabolic complications: • Hypocalcemia (citrate toxicity) in patients with liver or heart failure. • Hyperkalemia • Hypokalemia Transfusion transmitted infections (TTI) Other non immune Transfusion reactions:

42. The most common high-morbidity transfusion reaction encountered in clinical practice. Transfusion-associated circulatory overload (TACO) is a common transfusion reaction in which pulmonary edema develops primarily due to volume excess or circulatory overload Risk factors: old ages, renal disease, cardiac disease, and critically ill status. The symptoms of TACO can include shortness of breath (dyspnea), low blood oxygen levels (hypoxemia), leg swelling (peripheral edema), high blood pressure (hypertension), and a high heart rate (tachycardia) Transfusion Associated Circulatory Overload (TACO)

43.  Electrolyte imbalance can occur related to blood transfusion variations in serum potassium levels can have significant impact on cardiovascular and neuromuscular function. Hyperkalemia associated with blood transfusions => increased blood potassium levels Hypokalemia => Low blood potassium levels

44. Hyperkalemia associated with blood transfusions Transfusion-associated hyperkalemic cardiac arrest is a serious complication in patients receiving packed red blood cell (PRBC) transfusions .  Mortality from hyperkalemia increases with large volumes of   Packed red blood cells ( PRBC) transfusion, increased rate of transfusion, and the use of stored PRBCs. Transfusion-associated hyperkalemic cardiac arrest

45. Potassium in stored blood increases due to decrease in ATP production and leakage of potassium into the supernatant. Hyperkalemia and cardiac arrhythmias can occur in patients when  RBCs are transfused quickly, delivered directly to the heart without time for electrolyte equilibration, or accumulate extracellular K +  due to storage time . Recent research has focused on “stored blood” with growing concern that the age of an RBC unit (even with the current accepted shelf life of 42 days) may affect its safety profile Hyperkalemia associated with blood transfusions The risk of potassium overload can be minimized by  selecting only blood collected less than 5 d prior to transfusion and by washing any unit of blood immediately before infusion to remove extracellular potassium

46. Hypokalemia is more common than the hyperkalemia after transfusion because donor red cells re- accumulate the ion intracellularly. After transfusion, as active metabolism recommences ,  potassium  is taken up into the cells. This may result in hypokalaemia No treatment or preventive strategy is usually necessary. Hypokalemia was rarely reported as a transfusion-associated complication . Hypokalemia

47. Pre-washing of RBCs is an essential practice for reducing potassium load in irradiated PRBCs. Due to the limited availability of time for preparing washed PRBCs in urgent situations, trauma patients usually receive unwashed RBCs that lead to increased risk for post-transfusion hyperkalemia Cardiac arrest has been commonly reported in transfusion-associated hyperkalemia. Most cardiac arrests were reported in children and adult patients requiring massive blood transfusions. Hypokalemia was rarely reported as a transfusion-associated complication. Recent research has focused on “stored blood” with growing concern that the age of an RBC unit (even with the current accepted shelf life of 42 days) may affect its safety profile. SUM UP: Electrolyte imbalance related to blood transfusion

48. The microbiological safety of blood donations may be affected by donors' exposure to HIV, hepatitis B, hepatitis C and syphilis and other transfusion-transmissible infections (TTI). Pre-donation screening of blood donors for Transfusion Transmissible Infections (TTI) is   the practice by which a prospective donor is tested for the presence of one or more of the TTI agents by a single rapid or quick method, and donation is deferred if the test is reactive for any of the TTI markers Transfusion Transmitted Infection (TTI)

49.  This may be due to known or unknown agents, such as viruses. This may occur despite careful selection of donors and testing of blood. Donor selection criteria are designed to screen out potential donors with increased risk of infection with HIV, hepatitis, and syphilis , as well as other agents. These procedures do not totally eliminate the risk of transmitting these agents . Transfusion Transmitted Infection (TTI)

50. • Many advances have been made in the testing of blood donations for infectious diseases. • However, the risk of transmitting viral, bacterial, and parasitic diseases via transfusion still exists. • Infectious complications of transfusion remain an important area of concern in transfusion medicine. Infectious complications

51. Bacterial: Platelets> packed red blood cell ( PRBC) VIRAL: RESIDUAL RISK due to: Window period- eg : the window period for an HIV test refers to  the time between HIV exposure and when a test can detect HIV in your body . Genetic variability in the viral strains. Laboratory errors: minor cause. Infectious complications

52. Nucleic Acid Amplification Testing ( NAT ) is a highly-sensitive method of testing blood that is used to detect  Hepatitis C  virus ( HCV) The risk of post-transfusion Hepatitis B  and C ( HBV and HCV) infection decreased dramatically , to an estimated 1 in 60,000 to 1 in 100,000 risk before implementation of h epatitis C virus HCV NAT => transfusion is no longer considered a major risk factor for HCV transmission. Current Risk of Posttransfusion Hepatitis Nucleic Acid Amplification Testing (NAT)

53. Cytomegalovirus (CMV) may, unpredictably, be present in white- cell-containing components from donors previously infected with this virus. For at-risk recipients, the risk of CMV transmission by cellular components can be reduced by transfusing CMV seronegative or leukocytes-reduced components. Transmission of CMV by transfusion may be of concern in: Low-birthweight (≤1200 grams) premature infants born to CMV seronegative mothers In certain other categories of immunocompromised individuals, if they are CMV seronegative. Transmission of CMV Cytomegalovirus  ( CMV ) is a common virus for people of all ages; however, a healthy person's immune system usually keeps the virus from causing illness.

54. Bacterial contamination is believed to be the most common infectious source of morbidity and mortality related to transfusion. Most commonly caused by contaminated apheresis platelets and whole-blood-derived platelets. Bacteria are most often believed to originate with the donor, either from the venipuncture site or from unsuspected bacteremia (presence of bacteria in the bloodstream). Bacterial multiplication is more likely in blood components stored at room temperature than in refrigerated components. Bacterial Contamination