Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia

Should all septic patients be given systemic anticoagulation? No

“…It was assumed that this common polymorphism in European populations (4-6% carry one allele) would not benefit from APC as the active site for APC on factor V was altered (Arg506Gln) and this prevents factor V degradation by APC. Remarkably, in the first phase 3 trial, FVL heterozygotes randomized to the placebo group had a statistically better outcome than patients without FVL (13.9 vs. 27.9%; p < 0.05) [14]. This finding was recapitulated in genetically modified mice indicating that excess clotting risk with FVL was a balanced polymorphism accompanied by reduced risk of death from sepsis.…”

Aetiology of Venous Thrombosis

“…In addition, recent studies showed that FVL decreased risk of developing severe sepsis from infections to some extent, again another privilege to think of. That was also proved in animal models (Kerlin et al, 2003). …”

The Factor V Leiden mutation is associated with a higher blood haemoglobin concentration in women below 50 of the Malmö Thrombophilia Study (MATS)

“…Brian S et al 2003 [12] have shown decreased blood loss during cardiac surgery in patients carrying the FVLmutation, and recently published studies, on both mice and men, show beneficial effects of the FVL-mutation on the outcome of severe inflammatory diseases and sepsis [15][16][17]. polymorphisms, exerting both positive and negative evolutionary pressure.…”