Abstract

1. Recurrent occlusion after thrombolysis may be caused by thrombin receptor-mediated platelet thrombosis occurring in a residual stenosis. To test the relative importance of the platelet thrombin receptor under conditions of high shear and endothelial damage (the Folts model of intracoronary thrombosis) we used the specific thrombin inhibitor recombinant hirudin. 2. A critical coronary artery stenosis overlying an area of crushed endothelium was used in a repeated measures study of eight open-chest anaesthetized dogs. In the control period, recurrent thrombosis occurred at an average rate (+/- SD) of 4.4 +/- 1.4 ml/min2. Infusion of recombinant hirudin at 1.6 mg h-1 kg-1 abolished recurrent thrombosis in three dogs, but the thrombosis rate averaged 4.7 +/- 2.9 ml/min2 in the remaining five animals. 3. Haematological measurements demonstrated the activity of recombinant hirudin: thrombin time rose from 13 +/- 3 s to > 165 s universally (P < 0.01), partial thromboplastin time rose from 14 +/- 2 s to 29 +/- 10 s (P < 0.01). Bleeding time rose from 2.3 +/- 0.8 min to 4.7 +/- 1.8 min (P < 0.05). 4. It is concluded that specific thrombin inhibition, despite affecting coagulation, is relatively ineffective in preventing intracoronary thrombosis under conditions of high shear.

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

Publication typeJournal Article

Indexed MeSH termsAnimalsAntithrombinsBleeding TimeCoronary ThrombosisDogsHirudin TherapyPartial Thromboplastin TimeRecombinant ProteinsRecurrenceThrombinThrombin TimeTreatment Failure

Summary

Folts canine coronary stenosis model: recombinant hirudin 1.6 mg/h/kg abolished recurrent thrombosis in only 3 of 8 dogs despite robust pharmacological activity (thrombin time >165 s, prolonged aPTT, prolonged bleeding time) — supports the limits of thrombin-only blockade in platelet-rich high-shear thrombi.

Why This Matters for Hirudotherapy

This study examined recombinant hirudin as a specific thrombin inhibitor in a canine model of intracoronary thrombosis (Folts model, n=8, repeated measures) under conditions of high shear and endothelial damage. Despite confirmed systemic anticoagulant activity (thrombin time rising from ~13 s to >165 s, aPTT from ~14 s to ~29 s, both P<0.01, and bleeding time from ~2.3 to ~4.7 min, P<0.05), hirudin abolished recurrent thrombosis in only 3 of 8 dogs; the remaining five showed thrombosis rates comparable to control (4.7 ± 2.9 vs 4.4 ± 1.4 ml/min²). The abstract concludes that specific thrombin inhibition was relatively ineffective in preventing intracoronary thrombosis under high-shear conditions. Relevance to ASH's domain is indirect: the study evaluates recombinant hirudin but does not mention leeches or hirudotherapy. The study is limited by its small canine sample and single hirudin dose.