Hyperhemolytic Transfusion Reaction in Non-Hemoglobinopathy Patients and Terminal Complement Pathway Activation: Case Series and Review of the Literature.

Hyperhemolytic transfusion reaction (HHTR) is a severe, life-threatening hemolytic transfusion reaction where hemoglobin value after red blood cell (RBC) transfusion is lower than the pre-transfusion value. When HHTR occurs, mainly in patients with hemoglobinopathy, complement activation up to membrane attack complex (MAC) is strongly suspected. However, our knowledge of HHTR in patients without hemoglobinopathy is limited. In the present study, we retrospectively reviewed patients with the diagnosis of HHTR who were attended at our hospital between 2013 and 2016. We also performed a literature search to identify other reported cases of HHTR. Finally, the role of terminal complement pathway activation in the pathogenesis of HHTR was assessed by exposing endothelial cells in vitro to activated-patient plasma to analyze C5b-9 deposits by immunofluorescence. HHTR was diagnosed in 3 patients according to current criteria. Patients were treated with intravenous immunoglobulins (alone or in conjunction with rituximab and plasma exchange), and all of them recovered successfully. We retrieved from literature search 10 patients without hemoglobinopathy who developed HHTR. A marked increase of C5b-9 (MAC) deposition on endothelial cells (almost 2.5-fold increase versus control, P < .05) was observed with the plasma sample obtained from one of our patients. In conclusion, HHTR was a rare transfusion reaction that occurred in patients without hemoglobinopathy. We add more evidence that complement cascade activation up to MAC might play a role in the pathogenesis of HHTR.