Introduction to delayed transfusion reactions
Unlike immediate reactions that occur during or within 24 hours of a blood transfusion, delayed reactions have a more insidious onset, presenting anywhere from days to years later. These reactions can be immune-mediated, where the recipient's immune system reacts to foreign antigens from the donor, or non-immune, resulting from the physical properties of the blood product itself. The potential severity can range from mild to life-threatening, making clinical vigilance essential for any patient with a recent transfusion history who develops unexplained symptoms.
Delayed hemolytic transfusion reaction (DHTR)
This is the most common type of delayed immune-mediated reaction, typically caused by a secondary immune response. A patient previously exposed to a foreign red blood cell antigen develops antibodies that react to a subsequent transfusion, leading to the destruction of transfused red blood cells.
Clinical manifestations and diagnosis
- Onset: 3 to 28 days post-transfusion, most commonly around 7 to 10 days.
- Symptoms: Fever, unexplained anemia, jaundice, and dark urine. In sickle cell disease patients, it can mimic a vaso-occlusive crisis.
- Diagnosis: Often involves a positive post-transfusion direct antiglobulin test (DAT), antibody screen, elevated bilirubin and LDH, and decreased haptoglobin.
Management
Treatment is supportive, addressing symptoms like fever and dehydration, with management of renal function and electrolytes in severe cases. Future transfusions require antigen-negative blood products.
Transfusion-associated graft-versus-host disease (TA-GVHD)
This is an extremely rare but almost universally fatal complication resulting from donor lymphocytes attacking recipient tissues. Viable donor T-lymphocytes engraft and proliferate in the recipient, causing damage to skin, liver, and bone marrow.
Clinical manifestations and diagnosis
- Onset: Typically 8 to 10 days after transfusion, ranging from 2 days to 6 weeks.
- Symptoms: Maculopapular rash, fever, gastrointestinal issues, and pancytopenia due to bone marrow aplasia.
- Diagnosis: Confirmed by histopathological studies showing donor T-lymphocytes attacking recipient tissues.
Prevention and management
Prevention through irradiation of cellular blood products is the only effective strategy, especially for at-risk patients. Leukoreduction is insufficient for prevention.
Post-transfusion purpura (PTP)
This delayed immune reaction causes a sudden and severe drop in platelet count. It usually affects patients previously sensitized to platelet antigens (most often anti-HPA-1a) through prior pregnancy or transfusion. The antibodies destroy both transfused and the patient's own platelets.
Clinical manifestations and diagnosis
- Onset: Approximately 5 to 10 days after transfusion.
- Symptoms: Profound thrombocytopenia, purpuric rash, bruising, and mucosal bleeding.
- Diagnosis: Based on clinical presentation, recent transfusion history, severe thrombocytopenia, and lab confirmation of anti-platelet alloantibodies.
Management
High-dose intravenous immunoglobulin (IVIG) is the primary treatment. Plasmapheresis and corticosteroids may also be used. Platelet transfusions are generally ineffective.
Transfusion-related iron overload (Hemosiderosis)
This non-immune complication results from repeated blood transfusions over time. Since the body cannot excrete excess iron, it accumulates in organs, causing damage and dysfunction.
Clinical manifestations and diagnosis
- Onset: Symptoms appear after significant iron accumulation, often years after chronic transfusion therapy begins.
- Symptoms: Progresses from subtle signs to liver cirrhosis, cardiomyopathy, diabetes, and endocrine issues.
- Diagnosis: Involves monitoring serum ferritin and using cardiac and liver MRI to assess organ iron concentration.
Management and prevention
Prevention and management involve chelation therapy to remove excess iron. Regular monitoring of iron levels and organ function is crucial for chronically transfused patients.
Comparison of delayed transfusion reactions
| Feature | Delayed Hemolytic Transfusion Reaction (DHTR) | Transfusion-Associated Graft-Versus-Host Disease (TA-GVHD) | Post-Transfusion Purpura (PTP) | Transfusion-Related Iron Overload |
|---|---|---|---|---|
| Cause | Anamnestic antibody response to red blood cell antigens. | Engraftment of donor T-lymphocytes attacking host tissues. | Immune response to platelet antigens, destroying both donor and patient platelets. | Progressive accumulation of iron from repeated red blood cell transfusions. |
| Time of Onset | 3-28 days, peaking at 7-10 days. | 8-10 days, but can range from 2 days to 6 weeks. | 5-10 days. | Months to years of chronic transfusion therapy. |
| Key Symptoms | Fever, jaundice, unexplained anemia, dark urine. | Fever, maculopapular rash, pancytopenia, liver dysfunction, diarrhea. | Severe thrombocytopenia, purpuric rash, mucosal bleeding. | Fatigue, cardiomyopathy, liver cirrhosis, endocrinopathy. |
| Patient Population | Patients with previous transfusion or pregnancy history. | Immunocompromised patients, recipients of directed donations from relatives. | Most commonly multiparous women. | Patients requiring chronic, repeated transfusions. |
| Prognosis | Generally mild, but can cause significant morbidity; supportive care is usually sufficient. | Almost universally fatal; prevention is key. | Self-limiting but can be life-threatening; high response to IVIG. | Progressive organ damage if untreated; improved with chelation therapy. |
Conclusion
Delayed transfusion reactions are a varied group of complications occurring days to years post-transfusion. These include DHTR, the rare but fatal TA-GVHD, PTP, and iron overload in chronically transfused patients. Accurate diagnosis requires clinical suspicion, patient history, and laboratory tests. Prevention and timely management are crucial for patient safety. Further details on transfusion medicine are available through resources like the National Institutes of Health.
Expert review
Content reviewed by an expert in hematology and transfusion medicine for medical accuracy.
