Immunohematology - 08 Transfusion Reactions

IMMUNOHEMATOLOGY TRANSFUSION REACTIONS OUTLINE • Transfusion Reactions o Introduction o Following Recognition of a Suspected Transfusion Reaction o Acute, Immunologic Transfusion Reactions o Acute, Non-Immunologic Transfusion Reactions o Delayed, Adverse Effects of Transfusion (Immunologic) o Delayed, Adverse Effects of Transfusion (Non-Immunologic) o Autoimmune Hemolytic Anemias TRANSFUSION REACTIONS INTRODUCTION • A transfusion reaction is defined as any transfusion- related adverse event that occurs during or after the transfusion of whole blood, blood components, or human-derived plasma products. They are also classified according to the time interval between transfusion and the presentation of adverse effects. Transfusion reactions have different associated outcomes that can be the cause of increased morbidity or even mortality. Therefore, it is of utmost importance that all transfusion decisions be carefully evaluated for their appropriateness. • Many of the adverse events seen with transfusion are related to the fact that transfusion is the introduction of foreign cells into the recipient. • Non-cellular plasma and plasma-derived products involve the introduction of foreign proteins into the recipient that may cause a transfusion reaction. • It also carries the risk of transfusion-transmitted infection. • Transfusion reactions are classified according to o Time when reaction occur ▪ Acute - <24h ▪ Delayed - 3-6 days or 7-14 days o Hemolytic or Non-hemolytic o Presence of mediator ▪ Immune mediated (immunologic) ▪ Non-immune mediated (nonimmunologic) FOLLOWING RECOGNITION OF A SUSPECTED TRANSFUSION REACTION: • Immediately stop the transfusion if the infusion is still in process • Send appropriate specimens to the laboratory for a transfusion reaction investigation • Identify a possible hemolytic transfusion reaction • Checking the appropriate identification of the component bag, label paperwork and the recipient’s pretransfusion specimen • Repeating ABO testing on the post-transfusion sample • Visual inspection of the pre- and post-transfusion specimen • Results of these findings are then provided to the blood bank supervisor or medical director to determine if additional testing is required • Final assessment of the transfusion reaction is the responsibility of the medical director or an appropriate designee ACUTE, IMMUNOLOGIC TRANSFUSION REACTIONS ACUTE/IMMEDIATE HEMOLYTIC REACTIONS • Most severe and may be life threatening due to ABO incompatibilities o <1cc can result to immediate transfusion rxn • Decrease in haptoglobin and hemopexin • The associated hemolysis is intravascular • Mediators: IgM Abs (usually to BAO antigens), complement • S/S: fever, chills, hemoglobinuria, hemoglobinemia, dyspnea, hypotension • Most severe cases may result to DIC and renal failure o DIC - disseminated intravascular uncoagulation FEBRILE NON-HEMOLYTIC TRANSFUSION REACTION (FNHTR) • Increase temperature of greater than 1C after transfusion • Mild immunologic reactions that are caused by the interaction of recipient antibodies against HLA antigens on donor’s WBCs and platelets • Most common type of transfusion reactions • Most common S/S: fever and chills • Management/Prevention: used of leukocyte filters during transfusion; antipyretics (paracetamol) ALLERGIC TRANSFUSION REACTION • Second most common type of transfusion reactions • IgE-mediated • S/S: urticaria, erythema, hives, itching, anaphylaxis • Management/Prevention: administration of antihistamines before the transfusion; administer washed components ANAPHYLACTIC TRANSFUSION REACTION • Mediator: plasma proteins, antibodies to IgA (anaphylactic reaction) often before 10 mL of plasma have been infused • Management/Prevention: transfusion of IgA-deficient components NONCARDIOGENIC PULMONARY EDEMA • A.k.a TRALI (Transfusion-Related Acute Lung Injury) • Most consistent finding is anti-leukocyte antibodies (ALA) in donor or patient plasma • Management: transfuse leukoreduced components ACUTE, NON-IMMUNOLOGIC TRANSFUSION REACTIONS BACTERIAL CONTAMINATION • Caused by the endotoxins produced by the Gram-negative bacteria • Mostly associated with cold growing Yersinia enterocolitica Also with Pseudomonas spp. and Escherichia coli • The incidence of bacterial sepsis is highest with Y. enterocolitica

TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO) • Good example of iatrogenic (physician-caused) transfusion reaction • Common in patients with cardiac and pulmonary disease (at risk children and elderly px and which chronic normovolemic anemia, cardiac disease or sickle disease) • May lead to congestive heart failure and pulmonary edema DELAYED ADVERSE EFFECTS OF TRANSFUSION (IMMUNOLOGIC) DELAYED HEMOLYTIC TRANSFUSION REACTION (DHTR) • Characterized by the accelerated destruction of transfused RBCs • May be diagnosed 7-10 days (or 3-7 days in other references) after transfusion • Most commonly associated with a secondary (anamnestic) response • The associated hemolysis is generally extravascular • Mediators: IgG abs to Rh, MNS, Kell, Kidd, and Duffy TRANSFUSION-ASSOCIATED GRAFT VS. HOST DISEASE (TAGVHD) • These reactions occur when immunologically competent lymphocytes are transfused into an immunocompromised host • S/S: fever, liver problems, rash, and diarrhea • Management/Prevention: transfusion of irradiated blood components • Graft-versus-host disease (GVHD): GVHD occurs when WBCs in transfused blood attack the tissues of a transfusion recipient who has a severely weakened immunity. • Recipient’s immune system doesn’t recognize the white blood cells in the transude blood as foreign. This allows them to survive and attack the recipient’s body tissues • To prevent white blood cells from causing GVHD, donated blood can be treated with radiation before transfusion. POST-TRANSFUSION PURPURA • Rare transfusion reaction usually seen in older female patients who have been sensitized to platelet antigens, either by previous pregnancy or transfusion. • Characterized by severe thrombocytopenia one week after transfusion due to platelet specific antigens DELAYED, ADVERSE EFFECTS OF TRANSFUSION (NONIMMUNOLOGIC) TRANSFUSION-INDUCED HEMOSIDEROSIS • Iron deposition in vital organs seen in patients who are thalassemics and with chronic transfusions • Prevented by transfusion of neocytes, infusing iron-chelating agents such as desferrioxamine TRANSMISSION OF DISEASES • Hepatitis B, NANB Hepatitis (HCV), HIV, HTLV-1 (oncogenic retrovirus that causes adult T cell leukemia), CMV, EBV o Prevention: screening for blood-borne dse • Syphilis – although, transfusion of stored blood has not been shown to transmit the disease because spirochetes do not survive at ref temp for 72 hours. • Hepatitis A – occurrence is very rare. Infection by transfusion requires that the donor has viremia (occurs briefly at the same time of onset of acute illness) o Hepa A - acqwuired through fecal-oral route AUTOIMMUNE-HEMOLYTIC ANEMIAS (AIHA) WARM AIHA • Account for the majority of cases of AIHA • Antibodies involved are usually IgG and react best at 37C • DAT is always positive (with both IgG and C3d) • Most common Specificity – Anti-Rh • Site of Hemolysis – usually extravascular • If the antibody screen is positive, adsorption and elution studies may be necessary to determine if the antibodies are autoAbs, alloAbs, or both COLD AIHA • Second most common type of AIHAs • Usually IgM abs and may be benign or pathologic • PCH – Paroxysmal Cold Hemoglobinuria • Antibody involved is auto-anti-P IgG (the Donath-Landsteiner Ab = biphasic Ab) • Cold Hemagglutinin Disease (CHD) – usually with anti-I specificity (but occasionally anti-P) • Site of Hemolysis: usually intravascular • DAT is positive because of the presence of C3d on the RBCs DRUG-INDUCED AIHA • Drug Adsorption - abs are IgG and directed against drugs such as Penicillin that are adsorbed on to the surface of the RBCs • Immune complex type - abs to drugs such as quinine and quinidine for immune complexes with the drugs and activate complement C3d is found on the RBCs • Membrane modification - drugs such as cephalothin modify the RBC membrane and allow nonspecific adsorption of proteins • Methyldopa-induced/autoantibody formation - DAT is usually positive because of the presence of IgG on RBCs Ab/Complement Drug Drug Adsorption IgG Penicillin Immune complex Type C3d, complement, IgM/IgG Quinine, Quinidine Membrane modification Proteins Cephalothin Autab Formation IgG Methyldopa •