Hypofibrinolysis, protein C deficiency significantly increase VTE risk
MedWire News: Increased clot lysis time (CLT) combined with protein C deficiency is associated with a substantially increased risk for venous thromboembolism (VTE), study data show.
Participants with both prolonged CLT and protein C deficiency were 28 times more likely to have VTE than those with neither risk factor, report Edwin Bovill (University of Vermont, Burlington, USA) and colleagues in the Journal of Thrombosis and Haemostasis.
The researchers explain that increased CLT has been shown to increase VTE risk, but the genetic factors influencing this association are unknown.
They add that "the identification of genetic loci influencing CLT could increase our understanding of the fibrinolytic system, the interaction between the factors involved, and consequently our understanding of thrombotic disease itself."
The researchers evaluated CLT as a risk factor for VTE in the Vermont Kindred II (n=346), a pedigree that includes seven generations of descendants of a couple born in the 1830s suffering from a high thrombosis risk, partially attributable to a type I protein C deficiency.
The team found that protein C deficient family members had significantly shorter CLT than non-deficient members, at a median of 67 versus 75 minutes.
In addition, each standard deviation (SD) increase in CLT was associated with a 2.4-fold increased risk for VTE in protein C non-deficient family members, while protein C deficiency without elevated CLT increased VTE risk 6.9-fold.
The combination of increased CLT (1 SD) plus protein C deficiency raised the risk for venous thrombosis 27.8-fold, compared with family members with normal protein C levels and no prolonged CLT.
The researchers calculated that the heritability of CLT ranged from 42-52%, indicating that genetic factors contribute significantly to variance in CLT. Furthermore, multipoint linkage analysis revealed two loci, on chromosomes 11 and 13, which influenced CLT. Part of the linkage on chromosome 11 could be explained by the prothrombin 20210A mutation, which is known to influence CLT.
However, polymorphisms in the thrombin activatable fibrinolysis inhibitor gene -located on chromosome 13, and also associated with CLT - did not explain the variation in CLT observed.
Bovill and co-authors conclude that "hypofibrinolysis appears to increase thrombosis risk in this family especially in combination with protein C deficiency."
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By Laura Dean