A novel hirudin derivative inhibiting thrombin without bleeding for subcutaneous injection

Pharmacology study published in Thrombosis and Haemostasis (2016)

Última actualización: June 18, 2026Revisado por: ASH Editorial Board

Research article — evidence reviewArticle reference

Evidence: Observational studyDesarrollo de fármacosGenómica y proteómicaZhao B et al. · Thrombosis and Haemostasis, 2016

Abstract

Currently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro. When administered subcutaneously, DTIP showed potent and dose-dependent extension of aPTT, PT, TT and CT in rats (n=10 per group). The antithrombotic dose of DTIP induced significantly less bleeding than bivalirudin determined by transecting distal tail assay in rats. Furthermore, DTIP reached peak blood concentration in 0.5-1 hour and did not cause increased bleeding after five days of dosing compared to dabigatran etexilate. The antithrombotic effect of DTIP was evaluated in mice using lethal pulmonary thromboembolism model and FeCl3-induced mesenteric arteriole thrombus model. DTIP (1.0 mg/kg, sc) prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism from 30 % to 80 %. Intravital microscopy showed that DTIP (1.0 mg/kg, sc) decelerated mesenteric arteriole thrombosis caused by FeCl3 injury. These data establish that DTIP is a novel antithrombotic agent that could be used to prevent thrombosis without conferring an increased bleeding risk.

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

Publication typeComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

Indexed MeSH termsAnimalsAntithrombinsBlood CoagulationBlood Coagulation TestsChloridesCollagenDabigatranDisease Models, AnimalDose-Response Relationship, DrugEpinephrineFerric CompoundsHemorrhage

Resumen

Direct thrombin inhibitor peptide (DTIP) modeled on hirudin caused significantly less tail bleeding than bivalirudin or dabigatran etexilate while preventing lethal pulmonary thromboembolism in mice (survival 80% vs 30%) — first hirudin variant with significantly improved bleeding profile.

Por qué esto importa para la hirudoterapia

This study designed and evaluated a novel direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modeling, with its C-terminus interacting with thrombin exosite I and N-terminus with the active site. DTIP interfered with thrombin-mediated coagulation in human, rat, and mouse plasma in vitro and, when administered subcutaneously to rats, showed dose-dependent extension of aPTT, PT, TT, and CT. DTIP prevented deep venous thrombosis, increased survival in a lethal pulmonary thromboembolism mouse model from 30% to 80% at 1.0 mg/kg, and induced significantly less bleeding than bivalirudin in rat tail transection assays. The abstract does not mention hirudin or any leech-derived source for DTIP, so a direct relevance to hirudotherapy or the leech secretome cannot be established from the abstract alone; these are preclinical findings from animal and in vitro models only, with no human studies reported.

Citación

A novel hirudin derivative inhibiting thrombin without bleeding for subcutaneous injection.

Zhao B et al. · Thrombosis and Haemostasis, 2016

DOI

Contexto clínico relacionado

Explore cómo esta investigación se conecta con la práctica clínica

Drug Pipeline Drug Development Direct Thrombin Inhibitors Species Identification Taxonomy Salivary Gland Secretion Hirudin Anticoagulation Compounds Bivalirudin Oral Anticoagulants Hemostasis Dermatological Applications Dermatology Otolaryngology Post-Thrombotic Syndrome Pulmonology

Aviso legal — investigación y educación

La información en esta página se proporciona únicamente con fines educativos e informativos y no constituye asesoramiento médico, diagnóstico o recomendaciones de tratamiento. Los resúmenes de evidencia clínica reflejan la literatura publicada revisada por pares y no implican eficacia terapéutica fuera de los contextos autorizados por la FDA.

La autorización FDA 510(k) para sanguijuelas medicinales se limita a indicaciones específicas. Las aplicaciones en investigación y fuera de indicación se identifican como tales. Los profesionales deben consultar las directrices vigentes de la FDA, los protocolos institucionales y las normativas estatales aplicables antes del uso clínico.

ASH apoya la evaluación rigurosa basada en evidencia de todas las aplicaciones de hirudoterapia mediante ensayos clínicos controlados e investigación revisada por pares.

Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026