Innovative strategies for detection of uncharacterized platelet ligands from blood plasma and autoantibodies in blood

Platelets, plasma, and intravenous immunoglobulin (IVIG) are important blood products supplied by Canadian Blood Services (CBS). Platelets play center role in hemostasis and aggregate at sites of vascular injury to form a plug, which stops blood loss. Following transfusion, the interactions between plasma proteins with platelet surface receptors GPIbα and αIIbβ3 integrin direct the activity of platelets. Immune thrombocytopenia (ITP) is a bleeding disorder where autoantibodies target platelet surface receptors leading to a platelet clearance. Majority of ITP mediating autoantibodies target αIIbβ3 integrin but some also target GPIbα. The platelet clearance mechanisms differ between anti-αIIbβ3 and GPIbα mediated ITP leading to differing responses to available therapies (e.g. IVIG). The current “gold standard” test for platelet-autoantibodies is rarely clinically utilized due to the assay being complicated and unreliable. Recently we developed a novel antifouling molecular probe that has active GPIbα or αIIbβ3
integrin immobilized onto magnetic beads. We will use this method to identify uncharacterized plasma proteins that interact with GPIbα and αIIbβ3 integrin as well as develop a rapid assay to distinguish pathogenic antibodies in ITP. This study will lead to the optimized storage and transfusion of plasma products and, provide a rapid test for platelet antibodies leading the proper patient treatment.

NI, Heyu

St. Michael's Hospital

Postdoctoral Fellowship Program

Ontario

$162,400