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      Association between Thrombophilia and the Post-Thrombotic Syndrome

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      International Journal of Vascular Medicine
      Hindawi Publishing Corporation

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          Abstract

          The post thrombotic syndrome (PTS) is a chronic condition that develops in 20%–40% of deep vein thrombosis (DVT) patients. While risk factors that predispose to the development of venous thromboembolism (VTE) are widely known, factors that influence the development of PTS after DVT have not been well elucidated. Over 10% of the general population is affected by one or more identifiable inherited thrombophilias which have been shown to underlie at least 1/3 of cases of VTE. The various thrombophilias are important risk factors for VTE, but it is unknown whether they also increase the risk for development of PTS. We performed a review of studies that have reported on the association between thrombophilia and the development of PTS in populations of patients with DVT and with chronic venous ulcers. Studies vary with regards to the definition of PTS, study design, follow-up period, and present conflicting results. Based on these results, the question of whether thrombophilia predisposes to the development of PTS remains unanswered.

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          Most cited references55

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          Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

          The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.
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            High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.

            A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII. We studied 360 patients for an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants. Patients who had recurrent or secondary venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism. Recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001). Among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden or the G20210A prothrombin mutation, and the duration of oral anticoagulation. Patients with a high plasma level of factor VIII have an increased risk of recurrent venous thromboembolism.
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              Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization.

              The post-thrombotic syndrome (PTS) is increasingly recognized to be a common and important complication of deep venous thrombosis (DVT). Because there is no 'gold standard' objective test to establish its presence, PTS is diagnosed primarily on the basis of the presence of typical symptoms and clinical signs in a limb that was affected by DVT. As a wide variety of definitions of PTS have been used by researchers, it is difficult to compare data across studies and to formally combine data in meta-analyses. In a step towards standardization of the measurement of PTS in clinical studies, available scales and evidence to support their utility to diagnose PTS and to classify its severity were reviewed and discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis (Vienna, July 2008).
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                Author and article information

                Journal
                Int J Vasc Med
                Int J Vasc Med
                IJVM
                International Journal of Vascular Medicine
                Hindawi Publishing Corporation
                2090-2824
                2090-2832
                2013
                9 May 2013
                : 2013
                : 643036
                Affiliations
                Center for Clinical Epidemiology, Jewish General Hospital, 3755 Côte Saint Catherine Room H420.1, Montreal, QC, Canada H3T 1E2
                Author notes

                Academic Editor: Raghid Kreidy

                Author information
                https://orcid.org/0000-0002-3208-4283
                Article
                10.1155/2013/643036
                3665186
                23762560
                61d022b6-51fc-4b73-9684-ccc1543b9a2a
                Copyright © 2013 A. Rabinovich and S. R. Kahn.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2013
                : 4 April 2013
                : 17 April 2013
                Categories
                Review Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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