Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets
Research article published in International journal of molecular sciences (2023)
Abstract
Heparin-induced thrombocytopenia type II (HIT II), as stated in the literature, occurs in about 3% of all patients and in 0.1-5% of surgical patients. Thrombosis develops in 20-64% of patients with HIT. The mortality rate in HIT II has not decreased using non-heparin treatment with anticoagulants such as argatroban and lepirudin. An improved understanding of the pathophysiology of HIT may help identify targeted therapies to prevent thrombosis without subjecting patients to the risk of intense anticoagulation. The review will summarize the current knowledge about the pathogenesis of HIT II, potential new therapeutic targets related to it, and new treatments being developed. HIT II pathogenesis involves multi-step immune-mediated pathways dependent on the ratio of PF4/heparin and platelet, monocyte, neutrophil, and endothelium activation. For years, only platelets were known to take part in HIT II development. A few years ago, specific receptors and signal-induced pathways in monocytes, neutrophils and endothelium were revealed. It had been shown that the cells that had become active realised different newly formed compounds (platelet-released TF, TNFα, NAP2, CXCL-7, ENA-78, platelet-derived microparticles; monocytes-TF-MPs; neutrophils-NETs), leading to additional cell activation and consequently thrombin generation, resulting in thrombosis. Knowledge about FcγIIa receptors on platelets, monocytes, neutrophils and FcγIIIa on endothelium, chemokine (CXCR-2), and PSGL-1 receptors on neutrophils could allow for the development of a new non-anticoagulant treatment for HIT II. IgG degradation, Syk kinase and NETosis inhibition are in the field of developing new treatment possibilities too. Accordingly, IdeS and DNases-related pathways should be investigated for better understanding of HIT pathogenesis and the possibilities of being the HIT II treatment targets.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets.
Why This Matters for Hirudotherapy
This review summarizes current knowledge of the pathogenesis of heparin-induced thrombocytopenia type II (HIT II) and emerging treatment targets, reporting that HIT II occurs in about 3% of all patients and that thrombosis develops in 20–64% of affected patients. Notably for ASH, the authors observe that HIT II mortality has not declined despite treatment with non-heparin anticoagulants including lepirudin — a recombinant form of hirudin originally derived from the medicinal leech secretome — highlighting both the established role of leech-derived anticoagulants in managing this serious thrombotic complication and the limitations even of hirudin-based therapy. The review describes multi-step immune-mediated mechanisms involving platelets, monocytes, neutrophils, and endothelium, and discusses potential non-anticoagulant targets such as Fcγ receptors, Syk kinase, and NETosis pathways. However, this is a narrative review synthesizing existing literature rather than original research, and its observations about lepirudin outcomes reflect accumulated prior studies rather than new trial data.
Citation
Novel Knowledge about Molecular Mechanisms of Heparin-Induced Thrombocytopenia Type II and Treatment Targets
Mongirdiene A et al. · International journal of molecular sciences, 2023
Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026