Examining the Role of Complement in Predicting, Preventing, and Treating Hemolytic Transfusion Reactions

Abstract

Red blood cell (RBC) transfusion is a critical component of optimal management for a broad range of conditions. Regardless of the indication, pretransfusion testing is required to appropriately match RBC donors and recipients to provide immunologically compatible blood. Although this approach is effective in the vast majority of situations, occasionally, patients will inadvertently receive an incompatible RBC transfusion, which can result in a hemolytic transfusion reaction (HTR). In addition, patients with life-threatening anemia and a complex alloantibody profile, which precludes rapid procurement of compatible RBCs, may also receive incompatible RBCs, placing them at risk for an HTR. Despite the rarity of these clinical situations, when incompatible blood transfusion results in an HTR, the consequences can be devastating. In this review, we will explore the challenges associated with actively preventing and treating acute HTRs following incompatible RBC transfusion. In doing so, we will focus primarily on the role of complement, not only as a key player in HTRs, but also as a potential target for the prevention and treatment of HTRs.

Keywords: Alloantibody; Alloantigen; Complement; Hemolytic transfusion reactions; Sickle cell disease; Transfusion medicine, compatibility testing.

Fig 1.. Consequences of an incompatible RBC transfusion:

Antibody engagement of an antigen on an RBC surface can cause complement activation, which initially results in C3b deposition on the RBC surface and the release of C3a. C3b can bind additional complement proteins to initiate the membrane attack complex (MAC), which can ultimately result in intravascular hemolysis. C3b can also serve as a direct ligand for complement receptors, which, in addition to Fc receptor engagement of bound antibodies, can facilitate erythrophagocytosis. Receptor engagement of antibodies, C3b, C3a and Hemoglobin (Hb) (and its metabolites) can result in the activation of monocytes/macrophages and many other cell involved in immune function, directly contributing to the pathophysiology of a hemolytic transfusion reaction.