The Role of Single-Molecule Force Spectroscopy in Unraveling Typical and Autoimmune Heparin-induced Thrombocytopenia

For the last two decades, heparins have been widely used as anticoagulants. Besides numerous advantages, up to 5% patients with heparin administration suffer from a major adverse drug effect known as heparin-induced thrombocytopenia (HIT). This typical HIT can result in deep vein thrombosis, pulmona...

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Veröffentlicht in:International journal of molecular sciences 2018-04, Vol.19 (4), p.1054
Hauptverfasser: Bui, Van-Chien, Nguyen, Thi-Huong
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Sprache:eng
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Zusammenfassung:For the last two decades, heparins have been widely used as anticoagulants. Besides numerous advantages, up to 5% patients with heparin administration suffer from a major adverse drug effect known as heparin-induced thrombocytopenia (HIT). This typical HIT can result in deep vein thrombosis, pulmonary embolism, occlusion of a limb artery, acute myocardial infarct, stroke, and a systemic reaction or skin necrosis. The basis of HIT may lead to clinical insights. Recent studies using single-molecule force spectroscopy (SMFS)-based atomic force microscopy revealed detailed binding mechanisms of the interactions between platelet factor 4 (PF4) and heparins of different lengths in typical HIT. Especially, SMFS results allowed identifying a new mechanism of the autoimmune HIT caused by a subset of human-derived antibodies in patients without heparin exposure. The findings proved that not only heparin but also a subset of antibodies induce thrombocytopenia. In this review, the role of SMFS in unraveling a major adverse drug effect and insights into molecular mechanisms inducing thrombocytopenia by both heparins and antibodies will be discussed.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms19041054