Case Presentation: A 40-year-old African American female presented with dizziness. She was admitted at an outside hospital two weeks prior to admission for frank melena due to a bleed in the descending colon that eventually self-resolved. She was transfused two units of blood and discharged with a hemoglobin of 8.4 g/dL. She presented to our hospital one week later with persistent dizziness, fatigue and new “cola-colored” urine but with no recurrence of melena. She was found to have a hemoglobin of 7.6 g/dL with urobilinogen present on initial urinalysis. Hemolysis labs were consistent with extravascular hemolytic anemia. Peripheral blood smear revealed microspherocytes consistent with extravascular hemolysis and occasional bite cells. Type and screen was positive for anti-E and anti-M antibodies. Direct Coombs test was negative. Clinical suspicion was high for delayed hemolytic transfusion reaction (DHTR) given recent transfusion just two weeks prior to admission, and review of outside hospital records revealed negative anti-E and anti-M antibodies before she was transfused. The patient’s hemolytic labs continued to persist several days into admission with a nadir hemoglobin of 6.6 g/dL. Five days into admission, high-dose prednisone (1 mg/kg) was initiated. Patient’s hemoglobin and hemolysis markers eventually recovered several days after steroid initiation. She was discharged with a month-long steroid taper.
Discussion: Delayed hemolytic transfusion reaction can happen anywhere from 3-30 days after a transfusion and is likely due to previous exposure to a foreign erythrocyte antigen. Often these pre-formed antibodies are not detected on routine screening due to low titers. Anti-E and anti-M antibodies are generally considered clinically insignificant, however there have been rare cases of hemolytic reactions reported in the literature. In the case of our patient, the anti-M antibody found on type and screen was reactive at 37°C and could be clinically significant. These patients require additional screening prior to transfusion, but otherwise care is generally supportive. Although there are few studies reporting efficacy of corticosteroids, these medications can be trialed in patients with refractory courses. Prophylactic administration of rituximab has been used in sickle cell patients with recurrent DHTR.
Conclusions: It is important for clinicians to recognize the presentation of delayed hemolytic transfusion reaction in recently transfused patients, especially those with gastrointestinal bleeding, which may cloud the overall clinical picture. Our patient presented with anemia and dark or “cola-colored” urine after a recent transfusion which should prompt the clinician to consider hemolysis, as early recognition is important. Patients with suspected history of DHTR may require additional antigen screening prior to transfusion. Treatment is generally supportive but case report and anecdotal evidence suggest administration of corticosteroids and rituximab may accelerate recovery.