ABO Incompatibility vs Delayed Hemolytic Transfusion Reaction: Key Presentation Differences
ABO incompatibility presents immediately (within minutes to hours) with acute intravascular hemolysis, shock, and DIC, while delayed hemolytic transfusion reaction (DHTR) occurs 6-21 days post-transfusion with extravascular hemolysis, fever, jaundice, and often a paradoxical drop in hemoglobin below pre-transfusion levels.
Timing: The Most Critical Distinguishing Feature
ABO incompatibility is an acute hemolytic transfusion reaction occurring within 24 hours (typically within minutes) of transfusion 1.
DHTR manifests within 21 days post-transfusion, with most cases presenting around 6-8 days after blood administration 2, 3.
Clinical Presentation Differences
ABO Incompatibility (Acute Hemolytic Reaction)
Immediate symptoms include 1:
- Pain (chest, back, infusion site)
- Restlessness and anxiety
- Skin flushing
- Dyspnea
- Shock (hypotension, tachycardia)
- Nausea
Severe complications develop rapidly 1:
- Intravascular hemolysis with immediate hemoglobinuria
- Disseminated intravascular coagulation (DIC) with microvascular bleeding
- Acute renal failure
- Cardiovascular collapse
The pathophysiology involves complement activation (C3a, C5a) causing histamine and kinin release, leading to vasomotor instability and activation of the coagulation cascade 1.
Delayed Hemolytic Transfusion Reaction
Subacute presentation includes 2, 4, 3:
- Fever (high-grade, present in nearly all cases)
- Jaundice (yellowing of skin and sclera from bilirubin accumulation)
- Hemoglobinuria (dark or red-colored urine)
- Bone pain that can mimic vaso-occlusive crisis in sickle cell patients
- Profound anemia (median hemoglobin 49 g/L in pediatric series)
Laboratory hallmarks distinguish DHTR 2, 5, 3:
- Inadequate hemoglobin rise (<1 g/dL post-transfusion) or rapid fall back to pre-transfusion levels
- Significant LDH elevation (median 2239 IU/L) reflecting red cell destruction
- Relative reticulocytopenia or paradoxical reticulocytosis from baseline
- In sickle cell patients: accelerated HbS% increase with concomitant fall in HbA
- New red cell alloantibody detected (though notably absent in 49% of cases) 3
Mechanism of Hemolysis
ABO incompatibility: Intravascular hemolysis mediated by complement-fixing IgM antibodies causing immediate red cell lysis within the circulation 1.
DHTR: Primarily extravascular hemolysis mediated by IgG alloantibodies (commonly Kidd, Rh, Kell antigens), with red cells destroyed in the spleen and liver 6, 7.
Hyperhemolysis: The Most Severe DHTR Variant
Hyperhemolysis syndrome represents the most dangerous form of DHTR, where hemoglobin rapidly declines below the pre-transfusion level, indicating destruction of both transfused AND the patient's own red blood cells 2, 4, 7. This phenomenon does not occur with ABO incompatibility.
Monitoring in Anesthetized Patients
Critical difference: In anesthetized patients receiving transfusions, ABO incompatibility presents with hypotension, tachycardia, hemoglobinuria, and microvascular bleeding that require immediate recognition 2. DHTR would not manifest during the operative period but days later.
Common Pitfall
Do not confuse the timing: The key error is failing to recognize that ABO incompatibility is a medical emergency occurring during or immediately after transfusion, while DHTR is a delayed complication requiring high clinical suspicion when patients present with unexplained anemia and hemolysis days to weeks post-transfusion 2, 1. In DHTR, the antibody may be undetectable on initial screening (antibody evanescence), making diagnosis challenging 8, 3.