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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, 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.
Author: | Van-Chien Bui, Thi-Huong Nguyen |
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URN: | urn:nbn:de:gbv:9-opus-65139 |
DOI: | https://doi.org/10.3390/ijms19041054 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2018/04/02 |
Release Date: | 2022/11/25 |
Tag: | HIT; PF4; binding force; heparin- and antibody-induced thrombocytopenia; mechanism |
GND Keyword: | - |
Volume: | 19 |
Issue: | 4 |
Page Number: | 14 |
Faculties: | Universitätsmedizin / Institut für Immunologie u. Transfusionsmedizin - Abteilung Transfusionsmedizin |
Licence (German): | Creative Commons - Namensnennung |