Platelet-activating antibodies against platelet factor 4 (PF4) cause highly prothrombotic disorders with reduced platelet counts. In heparin-induced thrombocytopenia (HIT), these antibodies bind PF4–heparin complexes, causing heparin-dependent platelet activation. Less common autoimmune and spontaneous HIT variants that are triggered by heparin and nonpharmacologic polyanions, respectively, have atypical clinical features and antibodies with additional heparin-independent platelet-activating properties. […]