Interference of thrombin in immunological assays for hirudin specific antibodies
Research article published in Journal of immunological methods (2012)
Abstract
Recombinant hirudins (desirudin, lepirudin) are direct thrombin inhibitors administered as anticoagulants for heparin-induced thrombocytopenia (HIT) and venous thromboembolism (VTE) prophylaxis. Although these small polypeptides are widely used, concern exists over reports of antigenicity. In the largest study of r-hirudin immunogenicity to-date, we evaluated the prevalence, quantity and specificity of IgG immune responses to desirudin (15 mg SC q12h for as long as clinically required) in 245 surgical and medically-ill subjects enrolled in DESIRABLE, a multicenter, open-label, clinical trial of hospitalized patients requiring VTE prophylaxis. Sera obtained before and 30 days after desirudin administration were analyzed for IgG anti-desirudin by immunoenzymetric assay using immobilized desirudin to bind desirudin-reactive antibody and peroxidase conjugated monoclonal-anti-human IgG Fc to detect bound IgG antibody. Of 245 study subjects, 19 (7.7%) were antibody "responders" (>2-fold increase in IgG antibody levels with >50% inhibition by desirudin 30 days post-treatment). There were no differences between responders and non-responders in incidence of clinical outcomes or bleeding-related adverse events. Forty-six patients had detectable desirudin-reactive IgG antibody prior to treatment, with no significant increase in antibody levels after exposure and no increase in clinical events. The origin of pre-existing hirudin-reactive IgG antibody requires further investigation involving suspected anti-thrombin-thrombin interactions. These results indicate a low potential for immunogenicity, with <8% of patients developing IgG antibodies after desirudin administration for VTE prophylaxis. In contrast to reports on lepirudin, production of anti-hirudin antibodies to desirudin has no apparent effect on clinical events.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Recombinant hirudins (desirudin, lepirudin) are direct thrombin inhibitors administered as anticoagulants for heparin-induced thrombocytopenia (HIT) and venous thromboembolism (VTE) prophylaxis.
Por qué esto importa para la hirudoterapia
Este ensayo multicéntrico, abierto, en 245 pacientes hospitalizados que requerían profilaxis de TVE evaluó la prevalencia, la cantidad y la especificidad de las respuestas inmunitarias IgG frente a la desirudina, una hirudina recombinante e inhibidor directo de la trombina derivado del anticoagulante hirudina de la sanguijuela medicinal. El estudio halló que el 7,7 % (19/245) de los pacientes eran respondedores de anticuerpos tras la administración de desirudina, sin diferencias en los desenlaces clínicos ni en los eventos adversos relacionados con sangrado entre respondedores y no respondedores. Para la ASH y la hirudoterapia, este trabajo es directamente relevante porque la desirudina y la lepirudina son análogos farmacéuticos de la hirudina derivada de la sanguijuela, y la caracterización de su perfil de inmunogenicidad aporta información sobre consideraciones de seguridad para los anticoagulantes basados en el secretoma de la sanguijuela. Un matiz importante es que este estudio examinó un producto farmacéutico recombinante administrado por vía subcutánea para la profilaxis de TVE, no la terapia con sanguijuelas en sí, por lo que los hallazgos de inmunogenicidad podrían no trasladarse directamente a los contextos de aplicación de sanguijuelas vivas.
Citación
Interference of thrombin in immunological assays for hirudin specific antibodies
Hamilton RG et al. · Journal of immunological methods, 2012
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026