Arterial Thrombosis in Factor V Leiden or Activated Protein C Resistance. Clinical and Experimental Studies

Abstract: Abstract The last two decades has seen an avalanche of studies establishing Activated protein C (APC) resistance due to Factor V Leiden mutation as the most prevalent genetic risk factor, yet known, for venous thromboembolism. This has been documented in 20-60% of patients with deep vein thrombosis (DVT). Whether such propensity also exists in arterial circulation is still controversial. The general aim of the present thesis is to clearify some of the controversies that cloud the impact of APC resistance or Factor V leiden mutation on arterial thrombosis. Paper I showed a significantly high prevalence of APC resistance or factor V Leiden mutation in peripheral vascular patients compared to the control group (22.7% vs 12.2%). In Paper II, association between early occlusions of vascular reconstructions and Factor V Leiden mutation was shown. At one month, there was a two-fold risk of occlusion of vascular reconstructions compared to non-carriers (14% vs 7%, p=0.02). At one year, the same tendency was noted although not significant (22% vs 12%). Paper III, an experimental arterial thrombosis study with factor V Leiden mice, revealed increased thrombogenicity in mice with Factor V Leiden mutation and arterial injury. There was a significant relationship between time to occlusion (TTO) and genotype (p=0.002). TTO was highest in the wild type mice (TTO: homozygote