Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism - Prevalence and risk assessment

The inherited thrombophilias-deficiencies of protein C, protein S, and anti thrombin III and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The ai m of this study was to determine the prevalence of single and combined prot hrombotic factors in patients with idiopathic VTE and to estimate the assoc iated 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 IT G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specifi c polymerase chain reactions and restriction enzymes. Activities of antithr ombin Ill and protein C, free protein S antigen, and lupus anticoagulant we re determined hr a subset of 109 patients who were not receiving oral antic oagulants. The prevalences of heterozygotes and homozygotes for factor V G1 691A and factor II G20210A among patients and controls were 40.1% versus 3. 9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozy gotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025 ). Heterozygous and homozygous factor V G1691A, factor IT G20210A, and homo zygous 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 in terval [CT], 22.1 to 155.2) for joint occurrence of factor V and factor LI polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphi sms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Am ong 109 patients in whom a complete thrombophilic work-up was performed, 74 % had at least I underlying defect. These data indicate that in most patien ts referred for evaluation of thrombophilia due to idiopathic VTE, I or mor e underlying genetic predispositions were discernible. The presence of >1 o f the prothrombotic polymorphisms was associated with a substantial risk of VTE.