Hemolytic transfusion reaction

HTR

1. Hemolytic transfusion reaction Dr Shreyas kate

2. Transfusion Reactions TRANSFUSION REACTIONS Acute Hemolytic reactions Non Hemolytic Febrile Reactions Allergic Reactions Delayed Hemolytic Reaction

3. Article Journal: The New England Journal of Medicine Published : July 11, 2019 Authors: Sandhya R. Panch , M.D., M.P.H., Celina Montemayor‑Garcia, M.D., Ph.D., and Harvey G. Klein, M.D.

4. INTRODUCTION 15℅ of inpatients receive blood transfusion 1 ℅ of them suffer severe adverse effects 5℅ – Hemolytic transfusion reaction Bystander Hemolysis

5. HISTORY Mid 17 th Century – First documented reaction Landsteiner’s discovery of ABO blood groups in 1900 Ottenberg - Routine pretransfusion testing Development of anticoagulant–preservative C ombination of serologic techniques and molecular identification of the correspo n ding red-cell genes ( compatibility testing)

6. Epidemiologic Features Hemolysis was the most common cause of transfusion-associated death during the 1976–1985 Least common fatal complications (1/1,972,000) red-cell units transfused in 2016 “Wrong blood in the tube” Delayed hemolytic reaction- 1 in 500 to 1 in 1000

7. PATHOPHYSIOLOGY Acute hemolytic reactions: Pre-existing IgM, and less commonly IgG Complement Activation (C5 through C9) Hemolysis Increased free Hgb ATN

8. Pathophysiology Delayed hemolytic reaction: Incomplete complement activation (C3a and C5a) Proinflammatory cytokines Bradykinin and Kallikrein system activation Vasodilation, Hypotension DIC

9. severe hemolytic reactions long-term transfusions part by the release of cell-free hemoglobin , activates leukocyte-driven inflammasome pathways and causes endothelial dysfunction through nitric oxide scavenging post-transfusion haemoglobin levels falling below the pretransfusion values Pathophysiology

10. Passenger lymphocyte syndrome solid-organ transplantation Incompatibility between the donor’s plasma and the recipient’s red cells, “minor ABO incompatibility” viable donor B lymphocytes, termed “ passenger lymphocytes ,” develop 5 to 14 days after heart– lung, liver, kidney, intestinal transplantations, as well as after hematopoietic stem-cell infusions Pathophysiology

11. CLINICAL Suspected AHTR Signs & Symptom: Fever,chills,rigor , flank pain reddish urine ,hypotension, dyspnea , sense of “impending doom,” oliguria, anuria, bleeding Timing: minutes to hours after transfusion Stop transfusion immediately, repeat clerical check Ancillary tests: positive DAT, hemoglobinemia, hemoglobinuria , low haptoglobin, high LDH, elevated direct or indirect bilirubin, high D-dimers, increased fibrinogen, PT or PTT (if DIC is present), BUN, or creatinine Repeat and confirm ABO, Rh, antibody compatibility; repeat DAT Immune-mediated hemolysis : aggressive hydration Severe cases: pressor support, renal consultation, management of coagulopathies Perform Gram's stain and blood cultures to rule out acute Infections Rule out drug-induced hemolysis , nonimmune causes

12. CLINICAL Suspected DHTR Signs and symptoms: fatigue, pallor, jaundice Timing: 2 days to 1 month after transfusion or infusion Obtain detailed patient history: record of multiple or recenttransfusions , including IVIG, platelets, plasma; HSCT; history of alloimmunization, pregnancies, or transplantation Ancillary tests : new positive antibody screen, incompatible cross-match, decreased hemoglobin , positive DAT or IAT, low haptoglobin, high LDH, elevated indirect bilirubin, spherocytes or microspherocytes on peripheral smear, reticulocytosis Management : cautious transfusion with antigen-negative, cross-match– compatible units In severe cases: immune modulators (glucocorticoids, IVIG, rituximab, erythropoietin-stimulating agents)

13. Management Supportive care Prompt interruption of the transfusion Saving of the remaining blood in the unit for testing Blood and Urine sampling ICU along with a renal consultation (dialysis)

14. Vigorous hydration with isotonic saline Maintain urine output at a rate above 0.5 to 1 ml/kg/hr ? Mannitol Supplemental diuretics Sodium bicarbonate (130 mmol per liter in 5% dextrose) at a starting at 200 ml /hr to achieve a urinary pH >6.5 Hyperkalemia Vasopressor : dopamine infusion (2 - 10 μ g /kg/min) Management

15. In DIC (bleeding, platelets, FFP and cryoprecipitate) platelet >20,000 per cubic ml INR < 2.0 fibrinogen > 100 mg/Dl No evidence supports the routine use of therapeutic high-dose glucocorticoids, intravenous immune globulin, or plasma exchange Management

16. Transfusion of incompatible units prophylaxis with glucocorticoids (hydrocortisone at a dose of 100 mg, administered just before transfusion and repeated 24 hours later) IV IG (1.2 to 2.0 g /kg, administered over a period of 2 to 3 days, with the first dose given just before the incompatible transfusion) Management

17. Sickle cell disease: Glucocorticoids IV Ig Rituximab Erythropoiesis-stimulating agents Life-threatening hemolysis : Plasma exchange Hemoglobin based red-cell substitutes eculizumab, Tocilizumab anti–IL 6 monoclonal antibody Management Newer agents : Heme scavengers 1.haptoglobin 2. hemopexin

18. Preventing passenger lymphocyte syndrome A recipient with blood group A receiving a transplant from a group O donor should receive group O red cells and group AB plasma Prophylactic plasma reduction in the donor graft, partial red-cell exchange Management

19. Prevention “zero tolerance” policies accepting blood samples without core identifiers Electronically generated labels Identification bands Repeating ABO checks Centralized transfusion databases

20. Patients who are already heavily alloimmunized and require long-term transfusion support, Prophylactic Rituximab (1 to 2 gm iv) Inj methylprednisolone Patients with sickle cell disease glucocorticoids intravenous immune globulin rituximab erythropoiesis-stimulating agents Prevention

21. SUMMARY HTR are important cause of transfusion-associated reactions and may be subclinical, mild, or lethal Electronic verification systems Other reactions Delayed hemolytic transfusion reactions, Hyperhemolysis Passenger lymphocyte syndrome in transplant recipients Preventive strategies Systematic protocols

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