Acute Hemolytic Transfusion Reaction

Acute hemolytic transfusion reaction is rapid destruction of transfused red cells by the recipient's preformed antibodies, usually within minutes to 24 hours of the transfusion. ABO incompatibility is the commonest and most dangerous cause. Naturally occurring IgM anti-A and anti-B bind the donor cells and activate complement through to the membrane attack complex, so cells lyse inside the vessels.

Group O recipients given group A red cells have the most severe reactions. Rarer causes are antibodies to Kidd, Kell and Duffy antigens, and passive transfer of donor antibody in group O plasma or platelets given to a non-O recipient.

Nearly all ABO-incompatible transfusions result from clerical or identification errors at the bedside or in the laboratory, such as a wrong sample, wrong patient or wrong unit. About 1 in 40,000 units is given to the wrong recipient, and about 1 in 1.8 million causes a fatal reaction. As little as 15 to 30 mL of incompatible blood can produce symptoms, and mortality rises with volume infused, so early recognition changes outcome.

Free hemoglobin, complement fragments and cytokines (IL-1, IL-8, TNF) drive fever, vasodilation and shock. Tissue factor release triggers disseminated intravascular coagulation, and renal vasoconstriction with pigment injury causes acute kidney injury. Complications: shock, disseminated intravascular coagulation, acute kidney injury (about 30% of severe reactions) and death.

• Onset within minutes of starting the unit, often after only 10 to 50 mL
• Fever and rigors, flushing, chest tightness, dyspnea, lumbar or flank pain, pain along the infusion vein, nausea and a sense of impending doom
• Hypotension, tachycardia, red or brown urine (hemoglobinuria) and oliguria
• Under anesthesia the only signs may be unexplained hypotension, diffuse oozing from the wound and dark urine
• Red flags: hypotension, bleeding at multiple sites, hemoglobinuria and oliguria

1. Immediate bedside check of the patient's wristband, the compatibility label and the blood bag against the request form. Any mismatch confirms a wrong-blood event.
2. Repeat ABO and RhD grouping on a fresh post-reaction sample and on the pre-transfusion sample, with repeat crossmatch against the implicated unit.
3. Direct antiglobulin test on the post-transfusion sample (positive, often mixed-field), and antibody screen with identification.
4. Evidence of hemolysis: pink or red plasma on visual inspection of a centrifuged sample, raised free hemoglobin and LDH, low or absent haptoglobin, raised indirect bilirubin and hemoglobinuria on urinalysis.
5. Coagulation tests: prothrombin time, activated partial thromboplastin time, fibrinogen (low) and D-dimer (high).
6. Renal and metabolic tests: creatinine, urea, potassium, bicarbonate and blood gases.
7. Blood cultures from the patient and Gram stain and culture of the bag, to exclude bacterial contamination.

Differentials, in order of exclusion: bacterial contamination, febrile nonhemolytic reaction, anaphylaxis, transfusion-related lung injury, circulatory overload, and hemolysis from other causes.

1. Stop the transfusion immediately, keep the cannula open with 0.9% saline, and keep the bag and set for the laboratory. Recheck the identity of every unit being given to other patients.
2. Resuscitation: 0.9% saline 20 mL/kg IV over 15 to 30 minutes (children 20 mL/kg), then 100 to 200 mL/h to keep urine output above 1 mL/kg/h (above 2 mL/kg/h in children), with a urinary catheter.
3. Renal protection: furosemide 40 to 80 mg IV once if urine output stays below 1 mL/kg/h after volume restoration (children 1 to 2 mg/kg IV). Avoid nephrotoxic drugs.
4. Hypotension: norepinephrine 0.05 to 0.5 micrograms/kg/min IV to a mean arterial pressure of at least 65 mmHg.
5. Coagulopathy: fresh frozen plasma 15 mL/kg IV, cryoprecipitate 10 units IV for fibrinogen below 1.5 g/L, and platelets (one adult dose) for counts below 50 × 10^9/L with bleeding.
6. Further red cell transfusion when needed: group O RhD-compatible red cells, crossmatched against the recipient's sample.
7. Hyperkalemia: calcium gluconate 10% 10 to 20 mL IV over 5 minutes, and insulin 10 units IV with 50 mL of 50% dextrose.
8. Renal replacement therapy for oliguric kidney injury with hyperkalemia, acidosis or fluid overload. In massive incompatible transfusion, exchange transfusion with compatible blood may be considered.
9. Fever and rigors: paracetamol 1 g IV or orally (children 15 mg/kg) once. Rigors: pethidine 25 mg IV once.
10. Reporting: inform the transfusion laboratory and the hospital transfusion team at once, and report the event as a serious incident to the hemovigilance system.

Prevention: positive identification of the patient at the bedside by two trained staff, using the wristband, request form and unit label, with electronic barcode checks where available. Follow-up renal function and hemoglobin until stable.