Single and Combined Prothrombotic Factors in Patients With Idiopathic Venous Thromboembolism

Abstract

Abstract-The inherited thrombophilias-deficiencies of protein C, protein S, and antithrombin III-and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (Pϭ0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (Pϭ0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of Ͼ1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE. (Arterioscler Thromb Vasc Biol. 1999;19:511-518.)

Laboratory Markers in the Diagnosis of Venous Thromboembolism

“…22 Others have suggested that this mutation is found in 5% to 15% of patients presenting with venous thrombosis and about 15% of patients being investigated for thrombophilia. 23,24 In my practice, those with a history of DVT had a 17.6% incidence of the defect, those with a history of PE had an 18.2% incidence, and those with current DVT had a 12% incidence of a positive defect.…”

Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors – a multicentre case–control study

“…Based on various trials, evidence is accumulating that familial thrombophilia, defined as a genetically determined tendency to thrombosis, may be as a result of a combination of clotting defects (Ehrenforth et al, 1999b;Nowak-Go Èttl et al, 1999;Salomon et al, 1999). In particular, evidence has shown that inheritance of FV G1691A combined with deficiencies of protein C, protein S and anti-thrombin, as well as with the PT G20210A variant, the MTHFR T677T genotype in some studies, or enhanced Lp(a) concentrations, further increases the manifestation of early vascular accidents in children and young adults.…”

Common Prothrombotic Gene Mutations in Cerebral Venous Sinus Thrombosis in North-West of Iran

“…This mutation was seen in 5% -15% of different races [13] [15] [16]. Salomon et al studied patients with idiopathic venous thromboembolism (VTE) and reported that the rate of MTHFR-C677T mutation was higher in VTE patients compared to healthy subjects (22.8% vs. 14.3%) [17]. The rate of MTHFR-C677T mutation in CVST patients has been reported to be about 12.5% …”