Sociedad Americana de Hirudoterapia

Anticoagulant activity of a sulfated galactan: serpin-independent effect and specific interaction with factor Xa.

Research article published in Thrombosis and haemostasis (2009)

Última actualización: June 18, 2026Revisado por: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDesarrollo de fármacosFarmacología salivalGlauser et al. · Thrombosis and haemostasis, 2009

Abstract

An algal sulfated galactan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant action is due to promoting thrombin and factor (F)Xa inhibition by antithrombin and heparin cofactor II. Here, we evaluated the anticoagulant effect of the algal sulfated galactan using serpin-free plasma. In contrast to heparin, the sulfated galactan is still able to prolong coagulation time and delay thrombin and FXa generation in serpin-free plasma. We further investigated this effect using purified blood coagulation proteins, discovering that sulfated galactan inhibits the intrinsic tenase and prothrombinase complexes, which are critical for FXa and thrombin generation, respectively. We also investigated the mechanism by which sulfated galactan promotes FXa inhibition by antithrombin using specific recombinant mutants of the protease. We show that sulfated galactan interacts with the heparin-binding exosite of FXa and Arg-236 and Lys-240 of this site are critical residues for this interaction, as observed for heparin. Thus, sulfated galactan and heparin have similar high-affinity and specificity for interaction with FXa, though they have differences in their chemical structures. Similar to heparin, the ability of sulfated galactan to potentiate FXa inhibition by antithrombin is calcium-dependent. However, in contrast to heparin, this effect is not entirely dependent on the conformation of the gamma-carboxyglutamic acid-rich domain of the protease. In conclusion, sulfated galactan and heparin have some similar effects on blood coagulation, but also differ significantly at the molecular level. This sulfated galactan opens new perspective for the development of antithrombotic drugs.

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

Publication typeJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
Indexed MeSH termsAnticoagulantsBinding SitesBlood CoagulationCalciumCysteine EndopeptidasesFactor VFactor XaFactor Xa InhibitorsGalactansHeparinHumansIn Vitro Techniques

Resumen

An algal sulfated galactan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant action is due to promoting thrombin and factor (F)Xa inhibition by antithrombin and heparin cofactor II. Here, we evaluated the anticoagulant effect of the algal sulfated galactan using serpin-free plasma. In contrast to heparin, the sulfated galactan is still able to prolong coagulation time and delay thrombin and FXa generation in serpin-free plasma.

Por qué esto importa para la hirudoterapia

Este estudio mecanicista in vitro mostró que un galactano sulfatado de algas prolonga la coagulación incluso en plasma libre de serpinas, inhibiendo directamente los complejos de tenasa intrínseca y protrombinasa, y se une al exosita de unión a heparina del Factor Xa (con Arg-236 y Lys-240 como residuos clave) de una manera dependiente de calcio que se asemeja pero difiere estructuralmente de la heparina, lo que los autores plantean como una nueva vía para el desarrollo de fármacos antitrombóticos. Para ASH, esto es un paralelo claro a la historia de descubrimiento de fármacos del secretoma de sanguijuela: demuestra cómo un polisacárido natural no mamífero puede generar anticoagulantes nuevos y mecanísticamente distintos, la misma lógica por la cual las moléculas salivales de sanguijuela se explotan como precursores de fármacos. El trabajo es enteramente preclínico, utilizando proteínas purificadas, mutantes recombinantes y plasma en lugar de pacientes, y se refiere a un compuesto algal, no a un agente derivado de sanguijuela, por lo que solo respalda la justificación a nivel conceptual e implica ninguna eficacia clínica o aprobación.

Citación

Anticoagulant activity of a sulfated galactan: serpin-independent effect and specific interaction with factor Xa.

Glauser et al. · Thrombosis and haemostasis, 2009

Contexto clínico relacionado

Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026

Este sitio web proporciona información educativa y no constituye consejo médico, diagnóstico ni recomendaciones de tratamiento. La terapia con sanguijuelas medicinales conlleva riesgos clínicamente significativos y debe ser realizada únicamente por profesionales calificados bajo protocolos aprobados institucionalmente. La autorización 510(k) de la FDA para sanguijuelas medicinales se limita a indicaciones específicas; las discusiones sobre uso investigativo y fuera de indicación se señalan correspondientemente. Para orientación médica específica, consulte a un profesional de salud calificado.