Acquired von Willebrand syndrome in patients with overt hypothyroidism: a prospective cohort study.

Numerous case reports have been published on acquired von Willebrand syndrome (aVWS) in patients with hypothyroidism, but no prospective studies have been published. The aim of this study was to investigate laboratory and clinical characteristics of aVWS in patients with newly diagnosed overt hypothyroidism. An observational cohort study was performed between May 2007 and February 2012. Consecutive hypothyroid patients before or within the first 48 h of replacement therapy were enrolled. At inclusion, blood was sampled for coagulation tests and bleeding history was documented by means of a standardized bleeding questionnaire. Repeat samples were obtained after restoration of euthyroidism. The prevalence of aVWS, defined as von Willebrand factor antigen (VWF:Ag) ≤50% and/or VWF ristocetin activity (VWF:RCo) ≤50%, was calculated. Patients with aVWS were subsequently divided into severe (VWF:Ag and/or VWF:RCo ≤10%), moderate (VWF:Ag and/or VWF:RCo between 10 and 30%) or mild (VWF:Ag and/or VWF:RCo between 30 and 50%). A total of 90 patients were included among whom a prevalence of aVWS of 33% was found. There were no patients with severe aVWS. Eight patients (9%) had moderate aVWS and 21 (23%) had mild aVWS. Bleeding score was negatively correlated with both VWF:Ag (ß -0.32, P = 0.03) and VWF:RCo (ß -0.32, P = 0.02). After restoration of euthyroidism, VWF:Ag had significantly increased by 44%, VWF:RCo by 36%, factor VIII by 39%, and endogenous thrombin potential by 10%. aVWS has a high prevalence in hypothyroid patients. Highest bleeding scores in patients with lower VWF levels suggest clinical relevance.

Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia.

BACKGROUND: Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous thrombosis as well as bleeding. In addition to the different therapeutic strategies available, aspirin is often used to prevent platelet aggregation. OBJECTIVES: To quantify the benefit and harm of antiplatelet drugs for long-term primary and secondary prophylaxis of arterial and venous thrombotic events in patients with polycythaemia vera or essential thrombocythaemia. SEARCH STRATEGY: Our searched included the CENTRAL (The Cochrane Library, issue 1 2007), MEDLINE (1966 to 2007) and EMBASE (1980 to 2007) databases, online registers of ongoing trials and conference proceedings. The date of the last search was March 2007. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in patients with polycythaemia vera or essential thrombocythaemia, diagnosed by established international criteria, with data for at least one of the selected outcomes, were included. DATA COLLECTION AND ANALYSIS: Using a predefined extraction form, we collected and analysed the following data where appropriate: mortality from arterial and venous thrombotic events, mortality from bleeding episodes, fatal and non-fatal arterial thrombotic events, fatal and non-fatal venous thrombotic events, micro-circulation events, transient neurological and ocular manifestations, major and minor bleeding episodes, all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel). MAIN RESULTS: Two RCTs that investigated 630 patients with an established diagnosis of polycythaemia vera, with no clear indication or contraindication to aspirin therapy, were included in this review. The use of aspirin, compared with placebo, was associated with a lower risk of fatal thrombotic events (although this benefit was not statistically significant (OR 0.20, 95% CI 0.03 to 1.14)) and did not increase the risk of major bleeding (OR 0.99, 95% CI 0.23 to 4.36). No studies have been published in patients with essential thrombocythaemia or studying other antiplatelet drugs. AUTHORS' CONCLUSIONS: The available evidence suggests that the use of aspirin is associated with a statistically non-significant reduction in the risk of fatal thrombotic events, without an increased risk of major bleeding, when compared with no treatment in patients polycythaemia vera who have no clear indication or contraindication to aspirin therapy.

Clinical review: Thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review.

CONTEXT: Various changes in the coagulation-fibrinolytic system have been described in patients with an excess or deficiency of thyroid hormones. The purpose of this systematic review is to summarize the effects of hyperthyroidism and hypothyroidism on these systems. EVIDENCE ACQUISITION: All published case-control or interventional cohort studies that evaluated the effects of hyperthyroidism and hypothyroidism on the coagulation-fibrinolytic system in vivo were identified by a computer-assisted search of the MEDLINE and EMBASE electronic databases. A scoring system was used to divide studies into three quality categories: high, medium, and low quality. EVIDENCE SYNTHESIS: A total of 36 papers were included. Because in several papers more than one case-control study or both a case-control and intervention study were described, a total of 39 case-control studies and 24 interventional cohort studies were analyzed. No high-quality study was identified. Three (7.7%) case-control and eight (33.3%) cohort studies were of medium quality. A total of 19 tests were investigated in the medium-quality studies. These tests revealed a hypocoagulable state for overt hypothyroidism and a hypercoagulable state for overt hyperthyroidism. CONCLUSIONS: This analysis confirmed that clinically overt hyperthyroidism and hypothyroidism modify the coagulation-fibrinolytic balance, indicating that thyroid hormone excess or deficit is the probable main pathophysiological mechanism. Patients with overt hypothyroidism and overt hyperthyroidism appear to have an increased risk of bleeding and of thrombosis, respectively.

Abdominal obesity and the risk of recurrent deep vein thrombosis.

BACKGROUND: Abdominal obesity has been found to be associated with an increased risk of deep vein thrombosis (DVT). Whether patients with abdominal obesity have an increased risk of recurrence is currently unknown. METHODS: Patients with objective diagnosis of DVT and a life expectancy of greater than 6 months underwent measurement of the circumference of the waist. A waist circumference of greater than 102 cm for men and greater than 88 cm for women defined abdominal obesity. Information on age, gender, and on the presence of risk factors for DVT was collected. At follow-up, all patients underwent serial compression ultrasound of the lower limbs and were clinically evaluated every 6 months. RESULTS: One hundred patients were enrolled, 58 with abdominal obesity and 42 without. Mean age was 64.5 and 57.3 years, respectively (p<0.05). Percentage of male patients was 32.8% and 81.0% (p<0.01). Unprovoked DVT and transient risk factors rates were similar in both groups. Overall, recurrent DVT was documented in 29 patients, 16 in patients with abdominal obesity (27.6%) and 13 in patients without (31.0%). At the multivariate regression analysis HR for VTE recurrence in abdominal obese patients was 1.26 (95% confidence interval=0.47-3.4). CONCLUSIONS: Abdominal obesity does not seem to modify the risk of recurrent DVT.

The metabolic syndrome and the risk of venous thrombosis: a case-control study.

OBJECTIVE: The results of recent studies have suggested that patients with idiopathic venous thromboembolism (VTE) might be at increased risk of asymptomatic atherosclerosis and cardiovascular events. The metabolic syndrome is a cluster of risk factors for atherosclerosis. Its impact on VTE is unknown. METHODS: In a case-control study, consecutive patients with objectively confirmed deep vein thrombosis (DVT) and control subjects with objectively excluded DVT underwent clinical assessment for the presence of the metabolic syndrome according to the National Cholesterol Education Program criteria. The presence of known risk factors for DVT was documented. Patients with DVT secondary to cancer were excluded. The prevalence of the metabolic syndrome was compared between patients with idiopathic DVT and controls. RESULTS: We enrolled 93 patients with a first episode of idiopathic DVT and 107 controls. The mean age was 65.1 and 63.7 years, respectively. The metabolic syndrome was diagnosed in 50.5% of patients with idiopathic DVT and in 34.6% of controls [odds ratio (OR) 1.93; 95% confidence interval (CI) 1.05, 3.56]. After adjustment for age, sex, body mass index, and smoke, the metabolic syndrome remained independently associated with idiopathic DVT (OR 1.94; 95% CI 1.04, 3.63). In patients with secondary DVT, the prevalence of the metabolic syndrome was 27%. CONCLUSIONS: The metabolic syndrome may play a role in the pathogenesis of idiopathic DVT and may act as link between venous thrombosis and atherosclerosis.

Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature.

Venous thromboembolism (VTE) is one of the most relevant causes of maternal death in industrialized countries. Low molecular weight heparin (LMWH), continued throughout the entire pregnancy and puerperium, is currently the preferred treatment for patients with acute VTE occurring during pregnancy. However, information on the efficacy and safety of anticoagulant drugs in this setting is extremely limited. We carried out a systematic review and a meta-analysis of the literature to provide an estimate of the risk of bleeding complications and VTE recurrence in patients with acute VTE during pregnancy treated with antithrombotic therapy. The weight mean incidence (WMI) of bleeding and thromboembolic events and the corresponding 95% confidence interval (CI) were calculated. Eighteen studies, giving a total of 981 pregnant patients with acute VTE, were included. LMWH was prescribed to 822 patients; the remainder were treated with unfractionated heparin. Anticoagulant therapy was associated with WMIs of major bleeding of 1.41% (95% CI 0.60-2.41%; I) antenatally and 1.90% (95% CI 0.80-3.60%) during the first 24 h after delivery. The estimated WMI of recurrent VTE during pregnancy was 1.97% (95% CI 0.88-3.49%; I(2) 39.5%). Anticoagulant therapy appears to be safe and effective for the treatment of pregnancy-related VTE, but the optimal dosing regimens remain uncertain.

Thalassemia trait and arterial thromboembolic events: a systematic review and a meta-analysis of the literature.

BACKGROUND: An increased risk of venous thromboembolic events has been reported in thalassemic patients, in particular in patients with thalassemia intermedia. The association between ß-thalassemia trait and atherothrombotic cardiovascular events is not well established. METHODS: In a systematic review and meta-analysis of the literature, we evaluated the association between ß-thalassemia trait and arterial cardiovascular disease. Studies were identified from the MEDLINE and EMBASE (until July 2010) electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was evaluated with the I(2) statistic. RESULTS: Of the 354 identified articles, eight case-control studies were eligible for the analysis. ß-Thalassemia trait was associated with a reduced risk of arterial cardiovascular disease (OR 0.45; 95% CI 0.45-0.60). Heterogeneity among studies was low (I(2) = 13%). The protective effect of ß-thalassemia trait was confined to male patients (OR 0.39; 95% CI 0.24-0.62), and was not observed in female subjects (OR 0.89; 95% CI 0.52-1.53). CONCLUSIONS: ß-Thalassemia trait may act as a protective factor against the development of arterial cardiovascular and cerebrovascular disease in male subjects. Larger prospective studies are necessary to confirm these preliminary findings and to further investigate the mechanisms underlying this protective effect.