Identification of mechanisms leading to antibody independent RBC hemolysis

Hemolysis is the lysis of red blood cells (RBCs) with the subsequent release of cellular contents. It can be produced due to intrinsic RBC defects or by external causes of immune or non-immune nature. Antibody-mediated hemolysis is diagnosed by a positive direct antiglobulin test (DAT), and/or a positive indirect antiglobulin test (IAT) in cases where RBCs have been transfused to the patient. However, some patients still experience RBC hemolysis despite testing negative in both assays. One potentially fatal example of this phenomenon is the post-transfusion hyperhemolysis occurring in patients suffering from sickle cell disease. In this proposal, we seek to understand the mechanisms governing hemolysis in these seronegative individuals. We aim to identify the specific leukocyte population(s) and molecular mechanism(s) involved in hemolysis through functional assays, using primary blood cells isolated from patients. Establishing this cell-based diagnostic method will also lead to potential new therapeutic approaches. In the long term, our proposal goals could drastically reduce the adverse effects of blood product transfusion in Canadian patients suffering from hemolysis.

BRANCH, Donald

St. Michael's Hospital

Postdoctoral Fellowship Program

Ontario

$150,000