Signs and Symptoms of Delayed Hemolytic Transfusion Reaction
A delayed hemolytic transfusion reaction (DHTR) presents as a significant drop in hemoglobin within 21 days post-transfusion, typically accompanied by hemoglobinuria, jaundice, fever, and bone pain that can mimic a vaso-occlusive crisis in sickle cell patients. 1, 2
Timing and Definition
- DHTR occurs within 21 days post-transfusion, with most cases presenting around 6 days after blood administration 3, 4
- The reaction may develop as late as 4 weeks post-transfusion in cases of primary immune response 5
Cardinal Clinical Features
Hematologic Signs
- Significant hemoglobin drop below expected post-transfusion levels (inadequate rise <1 g/dL or rapid fall back to pre-transfusion levels) 3, 6
- Hemoglobinuria (dark or red-colored urine indicating intravascular hemolysis) 1, 2, 4
- Relative reticulocytopenia or paradoxical reticulocytosis from baseline values 3, 2
- In sickle cell patients: accelerated HbS% increase with concomitant fall in HbA post-transfusion 3, 2
Clinical Symptoms
- Jaundice (yellowing of skin and sclera from bilirubin accumulation) 1, 2, 4
- Fever (often high-grade, present in nearly all cases) 1, 4
- Severe bone pain (present in all patients in pediatric case series) 4
- Generalized body ache and malaise 7
- Exertional dyspnea and easy fatigability 7
- Headache 7
Laboratory Findings
- Significant LDH rise from baseline reflecting red cell destruction 3, 2
- New red cell alloantibody detected (though notably absent in many cases) 3, 4
- Positive direct antiglobulin test (DAT) 7, 6
- Anemia (often profound, with hemoglobin levels as low as 4-4.5 g/dL in severe cases) 7, 4
Critical Diagnostic Pitfall
The symptoms of DHTR closely resemble vaso-occlusive crisis in sickle cell disease patients, leading to diagnostic delay or misdiagnosis. 7, 4 Clinicians must maintain high suspicion for DHTR when evaluating any sickle cell patient with pain crisis symptoms within 21 days of transfusion.
Hyperhemolysis Syndrome (Most Severe Form)
- Hemoglobin rapidly declines below pre-transfusion level, indicating destruction of both transfused and the patient's own red blood cells 2
- Rapid decline of post-transfusion HbA level 3
- May progress to multiple organ failure and death if not recognized and treated promptly 7
Important Clinical Considerations
Antibody Detection Challenges
- In 5 of 8 pediatric cases, no new antibody was identified despite clear hemolytic reaction 4
- Only 2 of 8 cases had new alloantibodies possibly responsible for the reaction 4
- Antibodies may be weakly reactive or require enzyme-treated red blood cells for detection 4, 5
- Kidd antibodies are particularly notorious for causing DHTR and may be difficult to detect 6
Anesthetized Patients
- General anesthesia masks typical symptoms of transfusion reactions 3
- Monitor for hypotension, tachycardia, hemoglobinuria, and microvascular bleeding 3
- Assess urine output and color and peak airway pressure periodically during transfusion 3
Exclusion Criteria
DHTR diagnosis requires exclusion of alternative causes for hemoglobin drop and hemolysis 3, 1