Molecular mechanism underlines heparin-induced thrombocytopenia and thrombosis
Research article published in Progress in molecular biology and translational science (2010)
Abstract
Heparin-induced thrombocytopenia (HIT) with thrombosis is the most severe side effect of heparin administration. HIT patients may die or have permanent sequelae, such as a stroke or limb amputation. Contaminated heparin is associated with anaphylactic reactions and deaths by activating the contact system. It is also associated with high incidence of HIT via a yet unknown mechanism. This chapter shows that: (1) the contact system can be activated by a variety of unrelated molecules; (2) kallikrein directly cuts prothrombin to generate functional thrombin through contact system activation; and (3) while heparin contaminants, oversulfated heparin by-product (OS-HB), induce thrombin generation in both normal and HIT patient plasmas through contact system activation, authentic heparin induces thrombin activities only in HIT patient plasmas containing autoantibodies against protein/heparin complex. These data suggest that the negatively charged IgG/protein/heparin or OS-HB complex activate the contact system and produce thrombin in human plasma and thrombin partially activates the platelets allowing subsequent platelet activation through IgG/Fc receptor II signaling. The newly discovered mechanism of heparin-induced thrombin activity could explain the increased incidence of HIT in patients exposed to contaminated heparin. Furthermore, the assays used in these studies would be valuable for HIT diagnosis, prevention, and treatment.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Peer-reviewed clinical and outcomes research relevant to anticoagulation, leech therapy, and microsurgical flap management. Indexed in PubMed and verified against the NCBI record.
Why This Matters for Hirudotherapy
This work examines the molecular mechanism of heparin-induced thrombocytopenia (HIT) and thrombosis, reporting that the contact system can be activated by varied negatively charged molecules, that kallikrein can cleave prothrombin to generate thrombin via contact-system activation, and that oversulfated heparin contaminants drive thrombin generation in both normal and HIT plasma while authentic heparin does so only in HIT plasma containing anti-protein/heparin autoantibodies. For the hirudotherapy evidence picture it is useful background on a serious limitation of heparin-based anticoagulation and on the contact (intrinsic) coagulation pathway, the same pathway targeted by several leech-secretome anticoagulants, helping frame why direct thrombin and contact-pathway inhibitors are of scientific interest. As a caveat, this is a mechanistic review/chapter centered on heparin biology and human plasma assays rather than on medicinal-leech therapy, and it makes no claims about leech-derived treatments or clinical outcomes.
Citation
Molecular mechanism underlines heparin-induced thrombocytopenia and thrombosis.
Qian et al. · Progress in molecular biology and translational science, 2010
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