Heparin-Induced Thrombocytopenia During Extracorporeal Membrane Oxygenation

Abstract

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) is an immune-mediated adverse effect of heparin therapy. Two clinical entities of HIT can be distinguished: HIT I and HIT II. HIT I is a harmless pharmacologic phenomenon associated with decreased platelet count within 24–48 h after initiation of heparinization. Unlike HIT II, it is not associated with thrombosis and does not necessitate discontinuation of heparin. In contrast, HIT II can cause both bleeding and thrombotic complications. It is the most important and most frequent drug-induced immunologic thrombocytopenia. Besides orthopedic and vascular surgery patients, patients after cardiac surgery are at highest risk of developing HIT II (1–5%). Its clinical importance is based on its strong association with venous and arterial thrombosis and thromboembolism (heparin-induced thrombocytopenia with associated thrombosis, HITT). HIT is caused by the development of an IgG antibody that recognizes multimolecular complexes of platelet factor 4 (PF4) and heparin. This so-called heparin-PF4-IgG complex leads to platelet activation and release of additional PF4 from alpha granules in platelets when bound to the platelet Fc receptor. Note that heparin forms a necessary part of the complex leading the further PF4 release. PF4 released in excess binds to heparin-like molecules on the surface of endothelial cells leading to immunemediated endothelial cell injury and heightening the risk for HITT and disseminated intravascular coagulation (DIC). The mainstay of therapy in HIT/HITT is the avoidance of further exposure to heparin in any form, avoidance of platelet transfusions and deferral of vitamin-K-antagonists until platelet recovery. Early use of alternative anticoagulants is inevitable when the indication for anticoagulation persists or in individuals with HITT. Extracorporeal membrane oxygenation (ECMO) remains a last line life-saving therapeutic option in patients suffering from