Obesity as a risk factor in venous thromboembolism

PURPOSE: Whether obesity is an independent risk factor for pulmonary embolism or deep venous thrombosis has not been fully determined. METHODS: We used the database of the National Hospital Discharge Survey to further investigate the potential risk of obesity in venous thromboembolic disease. RESULTS: The relative risk of deep venous thrombosis, comparing obese patients with non-obese patients, was 2.50 (95% confidence interval [CI] = 2.49-2.51). The relative risk of pulmonary embolism was 2.21 (95% CI = 2.20-2.23). Obese females had a greater relative risk for deep venous thrombosis than obese males, 2.75 (95% CI = 2.74-2.76) versus 2.02 (95% CI = 2.01-2.04). Obesity had the greatest impact on both men and women aged less than 40 years. CONCLUSION: The data indicate that obesity is a risk factor for venous thromboembolic disease in men as well as women.     

Hyperlipidaemia and venous thromboembolism in patients lacking thrombophilic risk factors

To ascertain the potential contribution of serum lipids to the development of deep vein thrombosis (DVT), a case-control study was conducted in 143 DVT patients lacking thrombophilic risk factors and in 194 age- and sex-matched controls. DVT patients showed significantly higher body mass indices (BMI), and triglyceride levels than did controls (P < 0.001 and P = 0.045 respectively). Using multivariate analysis, BMI was the only variable which remained statistically different, thus the risk of DVT was associated with obesity (odds ratio = 2.49). These results were confirmed when additional control for fibrinogen and plasminogen activator inhibitor type 1 (PAI-1) was carried out in a subgroup of cases and controls. When idiopathic (n = 39) and secondary (n = 104) patients with DVT were compared, the former showed a higher mean age, a higher proportion of men, and higher cholesterol levels. Age, sex and total cholesterol were statistically different by multivariate analysis. After age was dichotomized as >or= 50 years and cholesterol >or= 5.69 mmol/l, all three variables constituted independent risk factors for idiopathic DVT, with odds ratios of 2.73 for ages >or= 50 years; 3.72 for men and 2.67 for cholesterolaemia >or= 5.69 mmol/l. Obesity thus constitutes an independent risk factor for DVT, possibly in part mediated through triglyceride, fibrinogen and PAI-1 effects on haemostasis. In addition, cholesterolaemia levels of >or= 5.69 mmol/l constitute an independent risk factor for idiopathic DVT.     

The risk of recurrent venous thromboembolism among heterozygous carriers of the G20210A prothrombin gene mutation

The G20210A mutation in the prothrombin gene is associated with an increased risk of a first venous thromboembolic episode; few data are available about the long-term risk for recurrent venous thromboembolism and it is not known whether or not carriers of the mutation should be recommended lifelong anticoagulant treatment after the first thrombosis. We investigated 624 patients, referred for previous objectively documented deep venous thrombosis of the legs or pulmonary embolism, to determine the risk of recurrent thromboembolism in heterozygous carriers of the G20210A mutation in the prothrombin gene after the first episode of venous thromboembolism. After exclusion of other inherited (anti-thrombin, protein C, protein S deficiency and factor V Leiden) or acquired (anti-phospholipid antibody syndrome) causes of thrombophilia, 52 heterozygous carriers of the prothrombin mutation were compared with 283 patients with normal genotype. The relative risk for recurrent venous thromboembolism was calculated between groups using a Cox's proportional hazard model. The patients with the prothrombin mutation had a risk for spontaneous recurrent venous thromboembolism similar to that of patients with normal genotype (hazard ratio 1.3; 95% CI, 0.7-2.3). The circumstances of the first event (spontaneous or secondary) did not produce any substantial variation in the risk for recurrence. In conclusion, the carriers of the prothrombin mutation should be treated with oral anticoagulants after a first deep venous thrombosis for a similar length of time as patients with a normal genotype.     

The prevention of pregnancy‐related venous thromboembolism

Pregnancy‐related venous thromboembolism (VTE) remains one of the leading causes of maternal mortality and morbidity in the developed world. There is a lack of high‐level data surrounding the use of thromboprophylaxis in pregnancy. In the UK, following the publication of the first Royal College of Obstetricians and Gynaecologists (RCOG) guideline for VTE prophylaxis during pregnancy and the puerperium in 2004, a fall in maternal deaths secondary to VTE was observed during the subsequent triennium (2006–2008). For the first time since 1985, VTE was no longer the most common cause of maternal death. Low‐molecular‐weight‐heparin (LMWH) is generally the agent of choice for thromboprophylaxis in this setting, and is considered safe and efficacious. The accurate risk stratification of women in order to allow the targeted provision of thromboprophylaxis is challenging. A number of international guidelines support risk assessment for pregnancy‐related VTE and the provision of LMWH for those who are deemed at sufficiently high risk. This review describes the importance of VTE in pregnancy and the puerperium, the part played by different risk factors and the role of thromboprophylaxis in this group of patients.     

FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian population

The absolute rate of recurrence of venous thromboembolism (VTE) is approximately 5% per year. There is a lower rate of recurrence in provoked VTE, and higher in idiopathic one. So far, there is no consensus whether hereditary thrombophilia should be considered as a persistent risk factor, and whether it requires long-term anticoagulant therapy. The aim of our study was to estimate the risk of recurrent VTE in patients carrying FV Leiden mutation in Serbian population.In retrospective study (1994-2006), we have evaluated the risk of recurrent VTE in 56 patients who are carriers of FV Leiden mutation, in comparison to group consisting of 56 patients non-carriers of FV Leiden mutation. Patients with FII G20210A and MTHFR C677T mutations, antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, malignancies and diabetes were excluded from the study.Recurrent VTE occurred in 44.6% of the patients, carriers of the FV Leiden mutations, vs. 26.7% in non-carriers group (P<0.05). The incidence rate was 3.7 and 2.2% per year, respectively. The estimated relative risk of recurrence for FV Leiden carriers was 1.67 (95% CI 0.99-2.81, P=0.049). The 60% of patients with mutation and only 13% without mutation develop rethrombosis during first year after discontinuance of therapy (P<0.01).In our study patients with symptomatic VTE who are carriers of the FV Leiden gene mutations have a higher risk of recurrent VTE than non-carriers. Our data suggest the importance of the FV Leiden mutation detection and the estimation of the clinical condition for successful secondary prophylaxis of VTE.     

The prevention of hospital-acquired venous thromboembolism in the United Kingdom

Hospital-acquired venous thromboembolism (VTE) remains the number one safety issue in hospitals and is estimated to cause more preventable deaths than the more publicized hospital-acquired infection. There has been a failure of implementation of thromboprophylaxis (TP), mainly because of lack of awareness among health professionals, despite the large number of evidence-based studies available. The situation in the UK is gradually changing because of tireless campaigning by politicians, a charity and key opinion leaders. In response, the Department of Health has issued a national risk assessment tool, and National Institute of Clinical Excellence (NICE) guidelines for the prevention of VTE in all hospitalised patients, which will be available in August 2009. Although NICE guidelines are only applicable in England, it is to be hoped Northern Ireland, Wales and Scotland will also follow. Despite this, the consensus of expert opinion is that TP needs mandating to prevent pockets of non-adherence. Low molecular weight heparins are currently the gold standard pharmacological agent for TP; but are likely to be superseded within the next 5 years by new classes of oral anticoagulants, such as dabigatran and rivaroxiban, which are already licensed for TP after orthopaedic surgery.     

Polymorphisms of the Z protein protease inhibitor and risk of venous thromboembolism: a meta-analysis

Two nonsense polymorphisms of Z-dependent protease inhibitor (ZPI; Serpina10) have been identified. To assess the risk of venous thromboembolism (VTE) associated with W303x and R67X Serpina10 mutations, we performed a meta-analysis of studies comparing the prevalence of these two mutations in VTE patients and in controls Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a random-effects model. Five studies involving 5000 patients were included. R67X and W303X mutations of Serpina10 were not associated with increased VTE risk (OR 1.63; 95% CI 0.84, 3.16 and OR 1.21; 95% CI 0.29, 4.98 respectively).     

Elevated albuminuria associated with increased risk of recurrent venous thromboembolism: results of a population-based cohort study

This study examined the risk of recurrent venous thromboembolism (VTE) in patients with elevated albuminuria. In 1997-1998, inhabitants of Groningen, the Netherlands, aged 28-75 years (n=85,421), were invited to participate in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study, an observational, population-based cohort study. Albuminuria was measured and VTE occurrence was monitored in responding subjects (n=40,856). Patients with first VTE between study entry and January 2009, identified through databases of the national registry of hospital discharge diagnoses, death certificates, regional anticoagulation clinic and medical records, were used for analysis. Of 351 subjects with first VTE, 37 subjects developed a recurrence during a median follow-up period of 3.3 (interquartile range, 1.1-6.4) years. The annual incidence of recurrence in subjects with elevated albuminuria (≥ 20 mg/l) was 5.00% [95% confidence interval (CI); 2.16-9.85], compared to 2.38% (95%CI; 1.59-3.41) in subjects with normal albuminuria (<20 mg/l). Hazard ratio for recurrence was 1.95 (95%CI; 0.89-4.30) after adjustment for age and sex. This hazard ratio was 3.35 (95%CI; 1.18-9.47) in patients with first unprovoked, and 1.12 (95%CI; 0.25-5.01) in those with a first provoked event. This study showed that subjects with elevated albuminuria who experience an unprovoked VTE are at an increased risk of recurrence, independent of age and sex.     

Treatment of venous thromboembolism with low-molecular-weight heparin

Summary There is now ample evidence to indicate that certain low-molecular-weight heparins given subcutaneously can replace continuous intravenous unfractionated heparin for the initial treatment of venous thromboembolism. The low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and a prolonged duration of action, permitting them to be given by a once or twice daily injection for the prevention or treatment of venous thrombosis. Furthermore, treatment does not require laboratory monitoring, thus eliminating the need for continuous IV infusion and permitting the early discharge of patients with venous thromboembolism. This should eventually lead to the outpatient treatment of venous thromboembolism. Studies to date indicate that low-molecular-weight heparin is more cost-effective than unfractionated heparin in the treatment of venous thromboembolism and the cost effectiveness will be increased by out-of-hospital treatment. At the present time, the findings associated with any individual lowmolecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins, and therefore each must be evaluated in separate clinical trials. The information to date is that low-molecular-weight heparin is safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. The decreased mortality rate seen in two clinical trials, particularly in patients with metastatic cancer, was quite unexpected. This requires further confirmation in larger prospective randomized trials.     

Prevention and treatment of venous thromboembolism in the elderly patient

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.     

The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis

Whether or not pregnant women with a previous episode of venous thromboembolism (VTE) should receive antithrombotic prophylaxis is a matter of debate. In order to estimate the rate of recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE) during pregnancy and puerperium we retrospectively investigated a cohort of 1104 women with previous VTE; after a single DVT or isolated PE, 88 of them became pregnant at least once without receiving antithrombotic prophylaxis. Overall, 155 pregnancies and 120 puerperium periods without prophylaxis were recorded. There were nine recurrences during pregnancy and 10 during puerperium, with a rate of 5.8% [95% confidence interval (CI) 3.0-10.6] and 8.3% (95%CI 4.5-14.6) respectively. In pregnancy, the rate of recurrence was 7.5% (95%CI 4.0-13.7) if the first VTE was unprovoked, related to pregnancy or to oral contraceptive use, whereas no recurrence occurred if the first VTE was related to other transient risk factors. In puerperium, the rate of recurrence was 15.5% (95%CI 7.7-28.7) in women with a pregnancy-related first VTE, with a risk 3.9-times higher than in the remaining women. Inherited thrombophilia was not associated with a statistically significant increase in risk of recurrence in pregnancy or in puerperium, yet the rate of recurrence in puerperium was 14.2% (95%CI 5.7-31.4) in overall carriers of factor V Leiden and 30% (95%CI 10.7-60.3) in carriers with a pregnancy-related first VTE, with a risk 6.8 times higher than in women without thrombophilia and with a non pregnancy-related first VTE.     

Current risk factors for asymptomatic venous thromboembolism in patients undergoing total hip arthroplasty

Abstract

Objective: A history of venous thromboembolism (VTE) is a risk factor for newly formed VTE after total hip arthroplasty (THA). However, its morbidity and association with postoperative VTE are not clear and, therefore, were investigated in this study.

Methods: Four-hundred and nineteen patients scheduled for primary THA were included. We preoperatively identified any VTE factors such as obesity, age, and history of VTE by interviewing and duplex ultrasonography for all patients, and the patients were assigned into ‘high-’ or ‘low-risk’ groups, that were the indication whether chemoprophylaxis was administered after surgery. Postoperative VTE was also examined on the day 7 by enhanced computed tomography (CT) for all patients.

Results: Preoperative VTE were detected in 48 patients (11.4%), and postoperative VTE were found in 44 (10.5%). Linear and multivariate logistic regression analysis revealed osteonecrosis and preoperative VTE were the independent factors associated with postoperative VTE (Odds ratio (OR) 1.0 e-7 and 5.00, respectively). In the survey of each risk group, only preoperative VTE was recognized as a risk factor for high-risk group, and longer operation time for low-risk group.

Conclusion: The present study confirmed high frequency of preoperative VTE which was still the strongest risk factor for postoperative asymptomatic VTE     

系统性红斑狼疮合并静脉血栓栓塞症临床相关危险因素分析

目的探讨系统性红斑狼疮（SLE）合并发生静脉血栓栓塞症（VTE）的临床相关危险因素。方法回顾性连续收集2008年1月至2012年2月期间在解放军总医院住院治疗的27例SLE并发VTE的患者入血栓组,并募集同期27例与血栓组性别、年龄、体质量指数（BMI）、生活方式等环境因素相匹配的不伴有VTE的SLE患者作为对照组,利用单因素统计学分析两组患者的静脉血栓形成相关临床危险因素（血小板计数、免疫功能、补体、合并低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征、肾性高血压、蛋白尿、血尿等）及实验室诊断指标[C-反应蛋白（CRP）、D-二聚体,白细胞计数、活化部分凝血活酶时间（APTT）、血浆凝血酶原时间（PT）、血浆纤维蛋白原（FIB）1的差异。结果与对照组相比,血栓组合并低蛋白血症（70．37％）、狼疮肾炎（74．07％）、肾功能不全（70．37％）、肾病综合征（55．56％）、肾性高血压（66．67％）的发生率均显著升高（P值分别为0．003,0．000,0．000,0．027,O．029）。血栓组患者的实验室检测指标CRP（7．19±9．23）mg／L和D．二聚体（6．32±5．75）mg／L均显著高于对照组（P值分别为0．004,0．000）。结论低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征及肾性高血压可能是SLE合并VTE的临床相关危险因素;CRP及D-二聚体可能成为SLE合并VTE的实验室诊断指标。     

慢性阻塞性肺病并发静脉血栓栓塞危险因素分析

目的 探讨COPD发生静脉血栓栓塞症（VTE）的高危因素与预防对策.方法 分析我院呼吸内科诊断为COPD并发VTE的65例住院患者的临床资料,实验组（COPD合并VTE组）和对照组（COPD无VTE组）就年龄、长期卧床、其他合并症、长期吸烟、低氧血症、长期口服或静脉糖皮质激素、COPD急性加重频繁、深静脉置管等多种因素进行组间比较,采用χ2检验两组间的差异性.结果 实验组与对照组比较,长期卧床（〉7天）、COPD急性加重频繁（〉3次/年）、长期口服或静脉应用激素和深静脉置管,经χ2检验,P〈0.05,差异具有统计学意义.结论 长期卧床、COPD急性加重次数频繁、长期口服和静脉应用激素和深静脉置管是COPD并发VTE的高危因素.     

恶性肿瘤并发静脉血栓栓塞症的临床分析

目的分析并发静脉血栓栓塞症(VTE)恶性肿瘤患者的原发肿瘤种类、分期、分化程度等,以识别高危患者,提高防治意识,减少VTE的发生。方法回顾性分析北京医院2003年1月至2013年1月期间并发静脉血栓栓塞症的恶性肿瘤患者的年龄、性别、基础疾病、原发肿瘤种类、病理类型、分化程度、TNM分期、化疗方案及预后等临床信息。结果在所有18 531例恶性肿瘤患者中,280例并发VTE,其中男性157例,女性123例,年龄(66.60±12.60)岁。包括单纯肺栓塞(PTE)41例,单纯下肢深静脉血栓形成(DVT)189例,PTE合并DVT 50例。肺癌82例,消化道肿瘤78例,泌尿系肿瘤32例,妇科肿瘤27例,血液科肿瘤27例,乳腺癌12例,其他部位肿瘤22例。相比未并发VTE肿瘤患者,并发VTE多见于肺癌、妇科肿瘤和其他肿瘤患者,差异有统计学意义(P0.05)。151例(53.9%)并发VTE肿瘤患者病理类型为腺癌;206例(73.6%)患者发生VTE时,肿瘤处于进展期;247例有明确TNM分期患者中Ⅲ~Ⅳ期患者187例(66.8%);144例有明确病理组织分化程度报告,中、低度分化程度者120例(85.4%)。至随访结束,共有130例患者死亡,中位生存时间为(24.0±7.8)个月,明确诊断VTE后3,6,9,12个月的累积死亡率分别为46.9%、69.2%、80.0%和82.3%。导致死亡的主要原因是肿瘤本身、肺栓塞和感染。结论肿瘤与VTE密切相关,腺癌、进展期肿瘤、分化程度低的肿瘤患者和化疗方案中含铂类药物者更易发生VTE,临床医师应注意对这部分患者进行VTE风险评估,采取必要的预防措施,减少VTE的发生。     

The VITA Project: C677T mutation in the methylene-tetrahydrofolate reductase gene and risk of venous thromboembolism

We evaluated the hypothesis that a common polymorphism of the methylenetetrahydrofolate reductase gene (C677T), which results in increased levels of plasma homocysteine, may be a putative risk factor for venous thromboembolism (VT). Sixty-five cases of VT and 130 controls, both identified within the framework of an epidemiologic survey on thrombophilia, the Vicenza Thrombophilia and Arteriosclerosis (VITA) Project, were genotyped for the mutation. No increased risk of VT was found in carriers of the mutation. We conclude that screening for the C677T mutation of the methylenetetrahydrofolate reductase gene should not be recommended in unselected patients with VT.