American Society of Hirudotherapy

Displacement of fibrin-bound thrombin by r-hirudin precludes the use of 131I-r-hirudin for detecting pulmonary emboli in the rabbit

Research article published in Thrombosis and haemostasis (1994)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Drug DevelopmentRubens FD et al. · Thrombosis and haemostasis, 1994

Abstract

Pulmonary emboli are detectable by filling defects in the pulmonary vasculature upon pulmonary angiography. Emboli derived from venous thrombi are rich in fibrin to which thrombin remains bound. Hirudin, a specific thrombin inhibitor, binds to thrombin to yield a 1:1 stoichiometric complex. We examined whether 131I-recombinant hirudin (r-hirudin) could be used to detect pulmonary emboli in rabbits. Clots were formed by re-calcifying rabbit plasma in vitro, and then injected (0.034 ml) into a femoral vein to lodge in the lungs. 131I-r-hirudin (29 +/- 4 microCi/kg) was injected intravenously but emboli could not be detected by gamma camera in real time. Post-mortem analysis of lung tissue showed that 131I-r-hirudin did not associate with emboli prepared with 125I-fibrin. Because of these findings, we used different techniques to look at the binding of hirudin to plasma clots. Clots formed in vitro were incubated with 131I-r-hirudin in the presence of equimolar amounts of 125I-albumin; specific binding of 131I-r-hirudin was not observed. Experiments with immobilized fibrin(ogen) showed that 125I-r-hirudin did not bind to and remain with fibrin-bound 131I-thrombin but did lead to the inactivation and displacement of up to 70% of bound thrombin as r-hirudin-thrombin complex; residual thrombin bound to fibrin remained active. Thus, released r-hirudin-thrombin complex is probably cleared rapidly from the region of the embolus in vivo; radioiodinated r-hirudin may not, therefore, be useful as a marker for detecting emboli.

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

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsAnimalsChromatography, AffinityFemoral VeinFibrinHirudinsIodine RadioisotopesLungMaleProtein BindingPulmonary EmbolismRabbitsRadionuclide Imaging

Summary

Displacement of fibrin-bound thrombin by r-hirudin precludes the use of 131I-r-hirudin for detecting pulmonary emboli in the rabbit.

Why This Matters for Hirudotherapy

This study investigated whether 131I-labeled recombinant hirudin could serve as an imaging agent to detect pulmonary emboli in rabbits, leveraging hirudin's specific 1:1 binding to thrombin within fibrin-rich clots. The radiolabeled r-hirudin failed to localize to emboli in vivo or bind specifically to in-vitro plasma clots because it inactivated and displaced up to 70% of fibrin-bound thrombin as a soluble r-hirudin-thrombin complex that was rapidly cleared from the embolus region. For ASH's domain, this study illuminates important pharmacodynamic properties of hirudin-thrombin interactions at fibrin surfaces, relevant to understanding how leech-derived anticoagulants behave at clot sites. However, the study is purely preclinical (rabbit model) and its findings are actually negative regarding a diagnostic application; no therapeutic hirudotherapy is involved.

Citation

Displacement of fibrin-bound thrombin by r-hirudin precludes the use of 131I-r-hirudin for detecting pulmonary emboli in the rabbit

Rubens FD et al. · Thrombosis and haemostasis, 1994

DOIPubMed

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