title: Single-molecule force spectroscopy applied to heparin-induced thrombocytopenia.
abstract: 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.
authors: 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.
authors: Thi-Huong
authors: TH
authors: Nguyen
mesh_terms: D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010978:Platelet Factor 4 / Q000378:metabolism; D000072760:Single Molecule Imaging / Q000379:methods*; D013816:Thermodynamics; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D010978:Platelet Factor 4; D006493:Heparin
keywords: PF4/heparin antibody; heparin-induced thrombocytopenia; platelet factor 4 (PF4); platelet-platelet interactions; single-molecule force spectroscopy