A case control study of deep venous thrombosis in relation to factor V G1691A (Leiden) and A4070G (HR2 Haplotype) polymorphisms.

Activated protein C resistance (APCR) is a significant risk factor for venous thromboembolism (VTE), with the factor V (FV) G1691A (Leiden) mutation accounting for the majority of inherited APCR cases. An additional FV polymorphism, A4074G (FV-HR2), reportedly increased VTE risk by some, but not all groups. We determined the prevalence of FV-Leiden and FV-HR2 SNPs in 126 patients with deep venous thrombosis (DVT), and 197 control subjects. Frequencies of FV-Leiden A and HR2 G alleles, together with FV-Leiden G/A and A/A (but not HR2 A/G) genotypes were significantly higher among patients. While no significant linkage disequilibrium was noted between FV 1691A and 4070G or A alleles, significantly higher prevalence of single-mutant 1691G/4070G and 1691A/4070A haplotypes were seen in patients. FV Leiden and FV HR2 haplotype are independent risk factors for DVT, and their coinheritance does not seem to increase significantly DVT risk imparted by either.

Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon.

Factor V G1691A (FV-Leiden) and prothrombin (PRT) G20210A single nucleotide polymorphisms (SNPs) were associated with venous thrombosis among Caucasians. We assessed the contribution of both SNPs to the genetic susceptibility of deep venous thrombosis (DVT) among Lebanese and Tunisian patients. Subjects comprised 198 DVT patients and 540 healthy controls from Lebanon and 126 Tunisian DVT patients and 197 control subjects; FV-Leiden (MnlI) and PRT G20210A (HindIII) genotyping was done by PCR-RFLP. While the prevalence of FV-Leiden mutant A allele and the G/A and A/A genotypes were significantly higher among DVT patients from Lebanon and Tunisia, the association of PRT G20210A with DVT was pronounced among Lebanese but not Tunisian patients. The prevalence of PRT G20210A mutant A allele (P < 0.001 vs. P = 181) and G/A genotype (P < 0.001 vs. P = 0.994) was significantly higher among Lebanese but not Tunisians, respectively. While FV-Leiden was a common genetic risk factor for DVT in both communities, the contribution of PRT G20210A to the genetic susceptibility of DVT differed among Lebanese and Tunisians, which underscores the need to determine prothrombotic gene polymorphisms associated with DVT among Arab and Mediterranean basin communities.

Utility of thrombin-generation assay in the screening of factor V G1691A (Leiden) and prothrombin G20210A mutations and protein S deficiency.

BACKGROUND: The thrombin-generation assay has a variety of clinical uses, including diagnosis of thromboembolism-related disease, and particular profiles are associated with thrombophilic risk factors. The aim of this study was to evaluate the use of this assay in screening and identifying patients who require specific thrombophilic testing. METHODS: We used a 2-step approach to perform specific thrombophilic testing and thrombin-generation assays on 169 consecutive patients. The first step was to identify particular profiles of thrombin generation corresponding to each type of thrombophilic risk factor and to determine the pertinent variables related to thrombin generation. We then performed ROC curve analysis for each predefined variable to determine the relevant cutoffs for identification of patients in need of further testing (negative predictive value, 100%). RESULTS: Suggestive profiles were seen in factor V Leiden (n = 49) and prothrombin (n = 12) mutations and in protein S deficiency (n = 12). ROC curves showed that factor V Leiden may be excluded when the difference between lag times obtained in the absence and presence of activated protein C (APC) is >1.5 min and that prothrombin G20210A may also be excluded when the peak thrombin concentration is 63%. CONCLUSION: The thrombin-generation assay represents a promising tool for screening thrombophilic risk factors, particularly in patients who are carriers of factor V Leiden or prothrombin G20210A mutations and patients with protein S deficiency.