Delayed Hemolytic Transfusion Reaction Without Detectable Autoantibodies or Alloantibodies: A Possible Role of Phosphatidylserine Exposure on Donor RBCs

Delayed hemolytic transfusion reactions (DHTRs) may occur when there is an antigen mismatch between transfused RBCs and recipient RBC antibodies where sensitized RBCs are cleared by macrophages or complement activation leading to immunoglobulin G (IgG) mediated hemolysis. Some DHTR etiologies remain unknown since there are cases of DHTR when an RBC autoantibody or alloantibody is absent. Mechanisms have been proposed to explain these types of cases of DHTR, including bystander or reactive hemolysis by hyperactive macrophages. Studies in patients with sickle cell disease (SCD) have shown abnormalities in the structure and function of the RBC membranes including exposure of phosphatidylserine (PS) leading to macrophage clearance of sickled erythrocytes. We report on a case demonstrating that DHTR may occur as a result of PS exposure on antigen-matched RBC, resulting in macrophage clearance and hemolysis without detection of autoantibodies or allo-antibodies. An in vitro measurement showed an increased exposure of PS on compatible donor RBCs using the patient's plasma, which may be responsible for increased hemolysis during DHTR.