Introduction: D-dimer assay, generally evaluated according to cutoff points calibrated for VTE exclusion, is used to estimate the individual risk of recurrence after a first idiopathic event of venous thromboembolism (VTE). Methods: Commercial D-dimer assays, evaluated according to predetermined cutoff levels for each assay, specific for age (lower in subjects <70 years) and gender (lower in males), were used in the recent DULCIS study. The present analysis compared the results obtained in the DULCIS with those that might have been had using the following different cutoff criteria: traditional cutoff for VTE exclusion, higher levels in subjects aged ≥60 years, or age multiplied by 10. Results: In young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age-adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event. Conclusion:The results confirm the usefulness of the cutoff levels used in DULCIS.
Behçet’s disease (BD) is a chronic inflammatory disease of unknown aetiology characterized by recurrent oral, genital aphthous ulcerations, uveitis, skin lesions and other multisystem affections associated with vasculitis. Different types of vessels, predominantly veins, can be affected in BD. The frequency of vascular lesions in BD, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%. In this review, various factors of thrombogenesis in BD, particularly pro- and antithrombotic endothelial and non-endothelial factors, factors of coagulation, platelet activation and rheological changes are presented and discussed from positions of Virchow’s triad of venous thrombosis. Despite advances in understanding of thrombogenesis in BD, still many issues of diagnosis and targeted preventive and therapeutic measures remain unresolved. Further studies are needed to clarify the pathobiology of BD-related thrombosis and to provide the clinicians with recommendations over the utility, safety and effectiveness of the antithrombotic therapy in BD.
Objective-Behçet disease (BD) is a vasculitis of unknown etiology, characterized by oral or genital aphtosis and uveitis.Homocysteine (hcy) is an independent risk factor for venous and arterial thrombosis. The association between hyperhomocysteinemia and thrombosis has been investigated in some studies in BD patients. However, information on this association is based only on the results of small studies with conflicting results. To overcome such limitations, we performed a metaanalysis comparing the plasma levels of hcy in BD patients with and without history of thrombosis. Methods and Results-We searched for all published studies using the Medline and Embase databases. Two reviewers performed study selection independently. Studies were included if hcy was measured in adult BD patients with and without thrombosis. Two reviewers independently extracted data on study and population characteristics. The mean value of hcy in BD patients and the presence of hyperhomocysteinemia in patients with and without thrombosis were collected. Association between thrombosis and hyperhomocysteinemia, and the mean difference of hcy levels in BD patients with and without thrombosis were calculated. Sixteen studies, for a total of 979 patients, were included. Hyperhomocysteinemia was more prevalent in patients with thrombosis than in those without (odds ratio 3.14; 95% CI 1.26 to 7.80) Mean levels of hcy were significantly higher in patients with thrombosis in comparison with patients without (mean difference 3.30 mol/L; 95% CI 2.09 to 4.51). This high prevalence of thromboses, known since the 1950s, 3 promoted several studies aimed at investigating their pathobiology. Endothelial injury itself, common to other vasculitis, cannot clearly account for thrombosis development, so a hypercoagulable state was early hypothesized and investigated. 4 In the last several years, several inherited or acquired factors causing hypercoagulability have been studied in patients with venous and arterial thromboembolic events. 5-7 These thrombophilic factors have also been studied in patients with BD with a history of thrombosis, and conflicting results were obtained. 8 -11 Recently, Ricart et al performed a metaanalysis evaluating the role of FV Leiden, prothrombin G2021A mutation, and the homozygous 677TT mutation of the methyltetrahydrofolate reductase as risk factors for venous thrombosis in BD patients. 12 In this study, FV Leiden and G2021A prothrombin mutation were found to increase the risk of thrombosis in these patients, whereas 677TT mutation of methyltetrahydrofolate reductase did not. Conclusion-OurThese findings are consistent with the results of recent studies performed in general populations in which the presence of 677TT mutation of methyltetrahydrofolate reductase is not a risk factor for venous thromboembolism in the absence of hyperhomocysteinemia. 13 On the other hand, in the general population, increased levels of homocysteine (hcy) have been reported to be an independent risk factor for venous thromboembolism in addition to c...
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