Nguyen Thi-Huong
Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
ZIK HIKE - Center for Innovation Competence, Humoral Immune Reactions in Cardiovascular Diseases, University of Greifswald, 17489, Greifswald, Germany.
J Mol Recognit. 2017 Mar;30(3). doi: 10.1002/jmr.2585. Epub 2016 Oct 28.
Heparin-induced thrombocytopenia (HIT), occurring up to approximately 1% to 5% of patients receiving the antithrombotic drug heparins, has a complex pathogenesis involving multiple partners ranging from small molecules to cells/platelets. Recently, insights into the mechanism of HIT have been achieved by using single-molecule force spectroscopy (SMFS), a methodology that allows direct measurements of interactions among HIT partners. Here, the potential of SMFS in unraveling the mechanism of the initial steps in the pathogenesis of HIT at single-molecule resolution is highlighted. The new findings ranging from the molecular binding strengths and kinetics to the determination of the boundary between risk and non-risk heparin drugs or platelet-surface and platelet-platelet interactions will be reviewed. These novel results together have contributed to elucidate the mechanisms underlying HIT and demonstrate how SMFS can be applied to develop safer drugs with a reduced risk profile.
肝素诱导的血小板减少症（HIT）在接受抗血栓药物肝素治疗的患者中发生率约为1%至5%，其发病机制复杂，涉及从小分子到细胞/血小板等多个因素。最近，通过使用单分子力谱（SMFS），对HIT的机制有了深入了解，该方法能够直接测量HIT相关因素之间的相互作用。本文着重介绍了SMFS在单分子分辨率下揭示HIT发病机制初始步骤的潜力。将回顾从分子结合强度和动力学，到确定风险与非风险肝素药物之间的界限，以及血小板表面和血小板 - 血小板相互作用等方面的新发现。这些新结果共同有助于阐明HIT的潜在机制，并展示了SMFS如何应用于开发风险更低、更安全的药物。
