Anti-GPIb- and anti-GPIIbIIIa- mediated immune thrombocytopenia: Mechanisms and actions of intravenous IgG (IVIG) and alternative therapies

Platelets are small blood cells important for bleeding arrest. When vessel injury occurs, platelets aggregate to form a plug and support coagulation. Immune thrombocytopenia (ITP) is a disease where one’s immune system mistakenly attacks and produces autoantibodies that destroy one’s own platelets, leading to increased bleeding risk. The autoantibodies mainly target two platelet surface proteins essential for platelet hemostatic function; GPIIbIIIa and GPIb. Currently, around 20-30% of patients are refractory to therapies. It is unclear whether antibodies against GPIIbIIIa and GPIb cause ITP by the same mechanism, whether antibodies targeting these different proteins can be effectively treated by the same therapies, or whether some patients have more severe bleeding than others due to the specific type of antibodies in their blood. We propose to investigate whether antibodies against GPIb and GPIIbIIIa act differently by i) Binding to different sites (epitopes) on GPIb and GPIIbIIIa, ii) changing their physical structure and function, or iii) affecting patients’ responsiveness to therapies (e.g. IVIG and TPO). This study has already and will continue to provide significant insights into development of new diagnostic/therapeutic methods in aim of effectively managing this disease while avoiding unnecessary consumption of CBS product IVIG (an expensive and limited resource).

NI, Heyu

St. Michael's Hospital

Intramural Research Grant Program

Ontario

$412,010