A detailed view of HIT disorder and therapy. There are three potential routes to TF-mediated thrombin generation, resulting in the final step of platelet–fibrin thrombi. On the left, the locus of current therapy directed at thrombin generation and action (T1) is compared with alternative and combination novel therapies geared to formation of the IC (T2) or inhibition of IC-mediated platelet activation (T3). Hep, heparin; HIT, heparin-induced thrombocytopenia; IC, immune complex; PF4, platelet factor 4; TF, tissue factor.