Diagnosis: Delayed Hemolytic Transfusion Reaction (DHTR)
This patient has a delayed hemolytic transfusion reaction (DHTR), characterized by the classic triad of hemolysis occurring days to weeks after transfusion, positive direct antiglobulin test, and evidence of red cell destruction with elevated indirect bilirubin and dark urine (hemoglobinuria). 1, 2
Clinical Reasoning
The timing and presentation are pathognomonic for DHTR:
- Temporal relationship: Symptoms developed days after the recent transfusion (not immediately), which is the hallmark of delayed versus acute reactions 3, 4
- Laboratory confirmation: The positive direct antiglobulin test (DAT) indicates antibody coating of red blood cells, while the elevated indirect bilirubin (total minus direct) reflects extravascular hemolysis 3, 5
- Hemoglobinuria: Dark urine represents intravascular hemolysis, seen in 94% of DHTR cases 4
- Inadequate transfusion response: Despite recent transfusion, her hemoglobin has dropped back to severely anemic levels, indicating destruction of both transfused and possibly native red cells 3, 4
Why Not the Other Options
ABO incompatibility (option b) causes immediate, catastrophic hemolysis within minutes to hours of transfusion with severe hypotension, DIC, and acute renal failure—not a delayed presentation days later 1, 2
Transfusion-transmitted bacterial infection (option a) presents with high fever, rigors, and septic shock during or immediately after transfusion, not days later with isolated hemolysis 1
Febrile non-hemolytic transfusion reaction (option d) causes fever and chills without hemolysis, negative DAT, and no elevation in bilirubin or hemoglobinuria 1
Critical Management Considerations
Avoid further transfusion unless life-threatening anemia exists, as additional transfusions may worsen hemolysis and potentially cause multiorgan failure and death 1, 2
If transfusion becomes absolutely necessary for hemodynamic instability or altered mental status:
- Use extended antigen-matched red cells (C/c, E/e, K, Jka/Jkb, Fya/Fyb, S/s) 1, 2
- Initiate immunosuppressive therapy concurrently 1, 2
First-line immunosuppressive therapy for life-threatening hemolysis includes 2, 6:
- IVIg: 0.4-1 g/kg/day for 3-5 days (up to total 2 g/kg)
- High-dose steroids: Methylprednisolone or prednisone 1-4 mg/kg/day
Supportive care should be initiated immediately 2:
- Erythropoietin with or without IV iron
- Folic acid 1 mg daily
- Aggressive hydration to maintain renal perfusion
Common Pitfall
The most dangerous error is transfusing additional blood without recognizing DHTR, as this can exacerbate hemolysis—additional transfusions were either ineffective or worsened hemolysis in published case series 4. The key is recognizing that hemoglobin dropping below pre-transfusion levels despite recent transfusion is the red flag for DHTR 3, 4.