American Society of Hirudotherapy

Heparin-binding exosite of factor Xa.

Research article published in Trends in cardiovascular medicine (2000)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDrug DevelopmentSalivary PharmacologyRezaie · Trends in cardiovascular medicine, 2000

Abstract

Recent studies have indicated that the basic residues Arg(93), Lys(96), Arg(125), Arg(165), Lys(169), Lys(236), and Arg(240) (chymotrypsin numbering) constitute an exosite in the catalytic domain of factor Xa that can effectively bind heparin only if the acidic N-terminal Gla domain of the proteinase was neutralized by physiological levels of calcium. Binding of a full-length heparin chain to this site of factor Xa in the presence of calcium makes a significant contribution to acceleration of the proteinase inhibition by antithrombin through a ternary complex bridging or template mechanism. Moreover, certain basic residues of this site, particularly Arg(165) and Lys(169), play a key role in factor Va and/or prothrombin recognition by factor Xa in the prothrombinase complex. This article reviews recent structural, mutagenesis and kinetic data that lead to identification of this exosite and discusses how the binding of protein or polysaccharide cofactors to this site of factor Xa can modulate the specificity and physiological function of this key coagulant enzyme in plasma.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, U.S. Gov't, P.H.S.
Indexed MeSH termsAntithrombinsCalciumFactor VaFactor XaFactor Xa InhibitorsHeparinHumansMacromolecular SubstancesProtein BindingProtein ConformationProthrombinSubstrate Specificity

Summary

Recent studies have indicated that the basic residues Arg(93), Lys(96), Arg(125), Arg(165), Lys(169), Lys(236), and Arg(240) (chymotrypsin numbering) constitute an exosite in the catalytic domain of factor Xa that can effectively bind heparin only if the acidic N-terminal Gla domain of the...

Why This Matters for Hirudotherapy

This review examines the heparin-binding exosite in the catalytic domain of factor Xa, identifying specific basic residues that bind heparin in the presence of calcium and contribute to antithrombin-mediated inhibition via a template mechanism, while also playing roles in factor Va and prothrombin recognition within the prothrombinase complex. The article reviews structural, mutagenesis, and kinetic data on how protein or polysaccharide cofactors binding to this exosite modulate factor Xa specificity and physiological function. For ASH's domain, this article is only indirectly relevant — it concerns heparin–factor Xa–antithrombin interactions mechanistically distinct from the direct thrombin inhibition by leech-derived anticoagulants. No leeches or leech-derived substances are mentioned; relevance is limited to structural context on coagulation factor biology.

Citation

Heparin-binding exosite of factor Xa.

Rezaie · Trends in cardiovascular medicine, 2000

DOI

Added to ASH library: May 28, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.