'Inactivating' PF4: A new approach to HIT treatment?

摘要

Current methods of treating heparin-induced thrombocytopenia (HIT) focus on treatment and prevention of thrombotic complications. In this issue of Blood, Sachais et al describe a novel therapeutic approach: pharmacologic disruption of PF4 tetramers essential for formation of immune complexes that are central to the pathogenesis. Despite significant progress in diagnosis and treatment, HIT remains an important cause of morbidity in patients treated with this widely used anticoagulant. Although thrombocytopenia is a hallmark of HIT, platelet counts are rarely low enough to precipitate bleeding; rather, thrombosis, occurring acutely or even weeks after discontinuation of heparin, is the major threat to affected patients. It is now well understood that antibodies specific for conformational changes induced in the CXC chemokine platelet factor 4 (PF4) when it binds to heparin or to another glycosaminoglycan (GAG) are central to HIT pathogenesis.