Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy
Mechanism study published in Blood (2011)
Abstract
Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Low-grade sustained coagulation activation via Factor V Leiden ameliorates glucose-induced podocyte apoptosis — supports hirudin therapeutic-window concept in DKD.
Por qué esto importa para la hirudoterapia
This study investigated how factor V Leiden (FVL), a prothrombotic mutation, affects diabetic nephropathy, finding that low levels of coagulation activation can protect podocytes and reduce albuminuria in mice. Notably, when diabetic FVL mice were treated with the leech anticoagulant hirudin, this nephroprotective effect was abolished. This finding is highly relevant to the American Society of Hirudotherapy as it highlights a context-dependent interaction where leech-derived anticoagulants may counteract protective thrombin pathways in specific disease states. The limitation is that these findings are primarily derived from animal models and in vitro experiments, and do not reflect the typical therapeutic applications of hirudin.
Citación
Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy.
Wang H et al. · Blood, 2011
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026