Proposed pathogenesis of HIT/T.

Resting platelets bind heparin and store platelet factor 4 (PF4) in dense granules. When platelets are activated, PF4 is secreted. PF4 binds to the platelet surface through heparin, forming antigenic complexes. HIT/T antibodies bind to these complexes through the Fab’ end while occupying the signal transducing FcRgIIA receptors on the same or neighboring platelets. This amplifies the process of platelet activation, releasing additional PF4 and generating procoagulant microparticles. PF4 released into the circulation binds to monocyte/macrophages and endothelial cell-associated heparin and/or other glycosasminoglycans generating binding sites for HIT/T antibody. Binding of HIT/T antibody promotes tissue factor expression by monocyte/macrophages and endothelial cell, further predisposing to thrombosis