Hyperhemolytic transfusion reaction syndrome (HHTR) has been appreciated in allo-immunized patients with sickle cell anemia. In these patients, transfusion precipitates hemolysis of both donor RBCs and the recipient's native RBCs, leading to post-transfusion hemoglobin level below baseline. Recognition is important because it is life-threatening and has unique management. Despite the severe degree of anemia, the most important treatment for HHTR is generally to halt the cascade of hemolysis by withholding transfusion. We present the first case series of HHTR in non-sickle cell patients observed in a tertiary academic medical center.

We reviewed records of four patients treated by one of us. We also retrospectively search for any additional patient charts from those with diagnosis of HHTR from 1996 to 2012 from institutional database and also searched patients under ICD-9 codes for hemolytic transfusion reactions (999.83 to 85) from 2009 to 2011. Patients with sickle cell disease were excluded. HHTR was defined as post-transfusion hemoglobin level below baseline accompanied by clinical and laboratory evidences of hemolysis, and the recurrence of HHTR after repeated transfusions.

Four non-sickle cell patients who fulfilled criteria of HHTR were identified. Mean age was 34.7. Three were African-Americans, one was Caucasian, and all were females. Two patients had iron deficiency anemia, one had systemic lupus erythematosus, and one had no past medical history. The average amount of transfused PRBC was 5.83±0.3units per person. After transfusion, hemoglobin reached nadir (mean decrease from baseline 38%) within two to three weeks of initial transfusion. Corrected reticulocyte counts were typically low (<2%). All had symptomatic hemolysis often accompanied by chills, jaundice, elevated LDH and unconjugated bilirubin. Post-transfusion analysis of allo-immunization revealed three patients with de novo development of multiple allo-antibodies. The most common alloantibodies were anti-C, c and E. Various therapies including IV steroid, IVIg and erythropoietin were applied, but the most effective management was withholding further transfusion. One patient with consecutive transfusions expired after severe hemolysis. Three patients survived from HHTR and hemoglobin recovered to 72% of their baselines.

We have demonstrated the first case series of HHTR in non-sickle cell patients and defined its clinical characteristics. HHTR in non-sickle cell patients results in 38% decline of hemoglobin within two to three weeks of transfusion. De novo development of allo-antibodies strongly suggests that the exaggerated destruction of self and non-self cells may be secondary to acute induction of allo-immunity against non-self RBCs and subsequent complement activation leading to bystander hemolysis of self RBCs. HHTR is a unique and lethal complication of transfusion which occurs in both sickle and non-sickle cell patients. Withholding transfusion is a crucial strategy to HHTR. Thus, it is important not to reserve the diagnosis to sickle cell patients of African-American descent, but to recognize that this can occur in any transfused patient.

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No relevant conflicts of interest to declare.