We investigated the risk of recurrence of venous thromboembolism in APC resistant patients heterozygous for FV Leiden and compared these patient groups with a group of patients, who had a history of venous thromboembolism, but had neither APC resistance nor the FV Leiden mutation.
The complex between activated protein C (APC) and the protein C inhibitor (PCI) is a sensitive indicator of the degree of activation of blood coagulation and higher concentrations have been measured in carriers of the FV Leiden mutation who were in the recovery phase after treatment for venous thromboembolism (VTE).
Because activated protein C resistance is a common risk factor for venous thromboembolism, we prospectively evaluated the activated protein C sensitivity ratio and factor V Leiden mutation in cancer patients with and without venous thromboembolism.
Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism.
Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%.
Here we have analysed 125 consecutive patients with incidental or recurrent venous thromboembolism for the presence of mutations at the cleavage sites for APC at amino acid positions Arg336 and Arg562 of factor VIII.
The combination of the PROC mutation with a PROS deficiency in two family members triggered venous thromboembolism at age 31 and 6 years, respectively.
Furthermore, the normalized activated protein C sensitivity ratio of 80% of the users of third-generation preparations fell within the 5th to 95th percentile of the normalized activated protein C sensitivity ratio of female carriers of factor V Leiden, a mutation that is associated with hereditary resistance to activated protein C and with an increased risk of venous thromboembolism.
In conclusion, high thrombin generation in the presence of APC, in women after a first event of VTE is indicative for an increased risk of a recurrence.
These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.
The levels of circulating activated protein C reflect in-vivo protein C activation, and a low level of activated protein C is a risk factor for venous thromboembolism.
The activated protein C (APC) resistance phenotype associated with an abnormal factor V Leiden (FVL), and the G20210A prothrombin gene mutation are the most common findings in patients with venous thromboembolism (VTE).