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- W2037224723 abstract "Unlike the deficiencies of the anticoagulant proteins antithrombin, protein C and S, rare in patients with venous thromboembolism (VTE; 5% altogether) and in the general population (less than 1%), both the gain-of-function mutations of the factor (F)V and prothrombin genes are common in patients with VTE (around 25 and 10%, respectively) and in the general population (3–7% and 3%) [1]. The high prevalence of these mutations has prompted a wider application of thrombophilia screening, not always appropriately. Who should to be screened, and what are the benefits of screening? As inherited thrombophilia predisposes to VTE, the first category of individuals who might benefit from screening are those who developed an episode of VTE. To establish whether or not thrombophilia screening is worthwhile in these patients one should first know whether or not results would influence treatment, and particularly the duration of anticoagulants. If patients with thrombophilia had a higher risk of recurrence after discontinuation of anticoagulants, a more prolonged period of treatment would be recommended. Unfortunately, data on the comparative risk of recurrent VTE in patients with or without thrombophilia are conflicting [2]. This issue has been tackled by means of several prospective studies in heterozygous carriers of FV or prothrombin mutations, some providing evidence in favor of an increased recurrence rate [3-6], others not [7-10]. Whether or not a longer duration of anticoagulant treatment is more efficacious than the conventional period of 3–6 months is still a matter of debate. Longer or indefinite anticoagulant treatment should perhaps be reserved for patients with ‘severe’ thrombophilia associated with a very high risk of VTE, like carriers of homozygous or double heterozygous gain-of-function mutations and those with quantitative (type I) antithrombin deficiency, particularly if VTE occurred in the absence of transient risk factors. This approach is biologically plausible, even though it is not evidence based. I purport that thrombophilia screening helps to decide on the usefulness of primary prophylaxis in the presence of transient risk factors in asymptomatic relatives of thrombosis patients diagnosed with thrombophilia [11, 12]. Prophylaxis with unfractionated or low molecular weight heparin is commonly given to all individuals older than 40–45 years during surgery, trauma or prolonged immobilization, since the risk of VTE increases with these conditions and age [1]. When these conditions occur in individuals younger than 40–45 years diagnosed with thrombophilia in the frame of family screening, they should be recommended primary antithrombotic prophylaxis after the age of 15 years [13, 14]. Knowledge of the existence of thrombophilia is also likely to benefit women during the postpartum period, when the risk of VTE is 10–15 times higher than during the whole period of pregnancy [15]. Antithrombotic prophylaxis should be given during puerperium in asymptomatic women with thrombophilia [16], and should perhaps be given during the whole gestational period in carriers of ‘severe’ thrombophilic states (see above) [17]. In addition, women diagnosed with thrombophilia during family testing could be counseled on whether or not they can be safely put on oral contraceptives or hormone replacement therapy. Apart from asymptomatic women with ‘severe’ thrombophilia, who should be discouraged to use oral contraceptives, those with other causes of thrombophilia should be informed of the relative risk of VTE due to the type of abnormality (e.g. sevenfold increased for FV Leiden), the risk due to the use of the pill (fivefold) and to the multiplicative effect due to the presence of both (20- to 30-fold) [18, 19]. The relative risk of VTE is also increased two- to threefold by hormone replacement therapy [20], and the older age and greater absolute risk of VTE of postmenopausal women has to be considered when this therapy is prescribed, especially in carriers of thrombophilia. It is up to the physician's communication skills to impart information in a clear, balanced, comprehensive and accessible form, without creating undue anxiety. What definitely happened after the discovery of the common polymorphisms in FV and prothrombin genes is an inappropriate request of thrombophilia screening in healthy individuals with no personal or family history of VTE. A typical example of such unjustified testing is the screening of healthy women before the prescription of oral contraceptives. It has been calculated that to prevent one episode per year of VTE, oral contraceptives should be withdrawn from 400 asymptomatic carriers of FV Leiden; to find them, approximately 10 000 asymptomatic women should be tested, and this is obviously not cost-effective [21]. Indiscriminate screening for FV Leiden in pregnant women is also not cost-effective [22]. As to hormone replacement therapy, this does increase not only the relative risk of VTE but also that of a second non-fatal myocardial infarction [20]. The presence of the prothrombin mutation, but not of FV Leiden, increases the risk of a second myocardial infarction in women with hypertension [23]. These findings should be confirmed before recommending screening for the prothrombin mutation. In conclusion, thrombophilia screening is likely to be useful in patients carrying a very high risk of VTE (such as homozygous carriers of FV Leiden or prothrombin mutation, and type I antithrombin deficiency), as it may improve clinical outcome through changes in the duration of anticoagulant therapy. In addition, family screening performed when thrombophilia is diagnosed in thrombosis patients allows for optimization of primary prophylaxis in asymptomatic carriers during high-risk situations. Moreover, counseling can be more focused in these women when oral contraceptives or hormone replacement therapy are considered. In other situations, screening is not useful and represents a waste of resources." @default.
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- W2037224723 date "2003-03-01" @default.
- W2037224723 modified "2023-09-30" @default.
- W2037224723 title "Pros and cons of thrombophilia testing: pros" @default.
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- W2037224723 doi "https://doi.org/10.1046/j.1538-7836.2003.00167.x" @default.
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