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Mechanisms of Venous and Arterial Thrombosis in Heparin-Induced Thrombocytopenia

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Abstract

Since the reports by Weismann and Tobin in 1958 and Roberts et al. in 1964 called attention to paradoxical thrombosis in patients treated with heparin, the thrombotic aspect of the heparin-induced thrombocytopenia syndrome (HIT) has been emphasized. Yet to this day, the mechanism of thrombosis associated with HIT (HITT) is unclear. It is important to understand the etiology of HITT because of its devastating clinical consequences. We believe one rational approach to understand the mechanism underlying HITTS is to invoke Virchow's triad: stasis, vascular injury and a hypercoagulable state. A hypercoagulable state exists in all HIT patients due to platelet activation by heparin antibody binding. Thrombin generation from platelet microparticles and exposed platelet phospholipid, coupled with stasis (elderly bedridden or otherwise sedentary ill patients who comprise the majority of the HIT population), provide two risk factors that can lead to venous thrombosis. A hypercoagulable state coupled with endothelial cell dysfunction due to injury from heparin antibody, activated platelets, leukocytes, platelet microparticles, complement, atherosclerosis or medical intervention can lead to arterial thrombosis. Of patients with HIT, HITT occurs in about 25%, suggesting that a second set of patient specific risk factors, in addition to the generation of pathological heparin antibodies, determine whether HITT will develop. Interaction between activated platelets and other platelets, and with endothelial cells, leukocytes, neutrophils, monocytes and cytokines are areas of research that may provide more specific characterization of the hypercoagulable state and vascular damage. Nuances involving genetic variation in platelets, endothelial cells and immune function are also likely to be a major component of the observed variability of this disease spectrum. Virchow's triad may explain the different manifestations of HITTS.

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Authors and Affiliations

  1. Department of Pathology, Loyola University Medical Center, Maywood, Illinois, 60153, USA

    Jeanine M. Walenga, Walter P. Jeske & Harry L. Messmore

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  1. Jeanine M. Walenga
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  2. Walter P. Jeske
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Walenga, J.M., Jeske, W.P. & Messmore, H.L. Mechanisms of Venous and Arterial Thrombosis in Heparin-Induced Thrombocytopenia. J Thromb Thrombolysis 10 (Suppl 1), 13–20 (2000). https://doi.org/10.1023/A:1027372901367

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