Inherited and acquired risk factors for venous thromboembolism

Venous thrombosis, or venous thromboembolism, comprises deep vein thrombosis with or without symptomatic pulmonary embolus. The development of symptomatic venous thrombosis is highly dependent on gene-environment interaction. In most instances this interaction results in hypercoagulability (the intermediate phenotype) sufficient to result in intraluminal clot formation (the disease phenotype). The genetic framework underlying venous thrombosis is complex, and there is a large material contribution from disease and interaction with environmental factors. For example, venous thrombosis is related to recent hospitalization in approximately half of all adult cases. After a first episode of venous thrombosis patients are 40 times more likely to suffer a further event compared with previously unaffected individuals. However, the risk differs between patients. Duration of anticoagulation (lifelong or not) should be made with reference to whether an episode of thrombosis was provoked and the presence of other risk factors. The results of testing for heritable thrombophilia rarely influence duration of treatment.     

Genetic risk factors of venous thromboembolism

Up to date several hereditary disorders have been identified as prothrombic risk factors. The most common inherited thrombotic disorders include activated protein C resistance (factor V Leiden), prothrombin G20210A mutation, hyperhomocysteinemia, deficiencies of protein C, protein S, antithrombin III, and thrombomodulin. This article focuses on the clinical and the laboratory aspects of some of the inherited venous thrombotic disorders including the factor V Leiden, prothrombin G20210A mutation and protein S deficiency.     

Epidemiology and risk factors of venous thromboembolism

Venous thromboembolism (VTE) is a common disorder that can affect apparently healthy as well as hospitalized patients. The actual incidence and prevalence of this disease are difficult to estimate because of its often silent nature. The clinical relevance of VTE is highlighted by the important rates of recurrence and mortality. The individual risk of VTE varies as a result of a complex interaction between congenital and transient or permanent acquired risk factors. Risk factors can be either intrinsic (e.g., age, obesity, history of VTE, or thrombophilia) or disease related (e.g., surgical procedures and medical disorders such as cancer, heart failure, or acute respiratory failure). The presence or absence of specific risk factors may play an important role in decisions about the type (and duration) of thromboprophylaxis/anticoagulation to be used.     

Mechanistic view of risk factors for venous thromboembolism

Venous thromboembolism is an episodic disease with an annual incidence of 2 to 3/1000 per year that is associated with a high morbidity and mortality. Risk factors for venous thromboembolism come in many guises. They fit into an extended version of Virchow's triad and they tilt the hemostatic balance toward clot formation. This can be achieved by decreasing blood flow and lowering oxygen tension, by activating the endothelium, by activating innate or acquired immune responses, by activating blood platelets, or by increasing the number of platelets and red blood cells or modifying the concentrations of pro- and anticoagulant proteins in the blood. In this narrative review we will discuss the known common risk factors within this pathophysiological framework.     

超声心动图诊断急性肺动脉栓塞的价值

目的 :分析评价床旁超声心动图 (ECHO)在急性肺动脉栓塞 (APE)诊断中的实用价值。方法 :采用经胸ECHO对临床怀疑APE的 5 8例患者在 4～ 6h内行床旁ECHO检查。结果 :超声直接检出主肺动脉及左右肺动脉主干近端血栓者 4例 ,均被外科手术或肺动脉造影证实。本组具有典型右心负荷过重超声征象者 15例 (其中包括具有超声直接征象的 4例 ) ,核素肺灌注 通气扫描提示为双肺多发性大面积栓塞。仅右房、右室轻度增大或肺动脉轻度增宽者 19例 ,ECHO无改变者 2 4例 ,但核素肺灌注 通气扫描均提示为肺段或亚段栓塞。结论 :ECHO能够发现主肺动脉、左右肺动脉干内附壁血栓直接提示肺动脉栓塞 ,或根据右室负荷过重表现间接提示肺栓塞的可能 ,但对肺段或亚段栓塞者超声不能作出或排除诊断。     

Digital venous angiography in the diagnosis of pulmonary thromboembolism

Twenty-five patients with the clinical suspicion of pulmonary thromboembolism underwent venous digital subtraction angiography (DSA) concurrently with selective conventional pulmonary angiography and the results were compared by two independent observers. Our conclusion is that venous DSA lacks adequate specificity and sensitivity for the diagnosis of pulmonary thromboembolism in subsegmental pulmonary arteries. Any benefit derived from this slightly less invasive technique is far outweighed by the decrease in technical detail when compared to the selective film screen method.     

Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism

BACKGROUND: In patients with a first symptomatic pulmonary embolism (PE), the risk of recurrence is unknown. We therefore investigated the risk of recurrence among patients with spontaneous symptomatic PE and among those with deep vein thrombosis (DVT) without symptoms of PE. METHODS: After discontinuation of secondary thromboprophylaxis for a first venous thromboembolism (VTE), we prospectively observed 436 patients for an average of 30 months. Patients with secondary VTE, natural inhibitor deficiencies, lupus anticoagulant, cancer, long-term antithrombotic therapy, vena cava filters, or pregnancy were excluded. The study outcome was objectively documented recurrent symptomatic VTE. RESULTS: Recurrent VTE was seen among 28 (17.3%) of 162 patients with symptomatic PE and among 26 (9.5%) of 274 patients with DVT without symptoms of PE. Compared with patients with DVT, the relative risk of recurrent VTE among patients with symptomatic PE was 2.2 (95% confidence interval, 1.3-3.7; P =.005). The relative risk was not affected by age, sex, presence of factor V Leiden or prothrombin G20210A, hyperhomocysteinemia, or high factor VIII levels. Compared with patients with DVT without symptoms of PE, patients with symptomatic PE had an adjusted relative risk of PE at recurrence of 4.0 (95% confidence interval, 1.3-12.3; P =.03). CONCLUSION: Patients with a first symptomatic PE not only have a higher risk of recurrent VTE than those with DVT without symptoms of PE, but are also at high risk of symptomatic PE at recurrence.     

肺血栓栓塞症延迟诊断相关因素概述

肺血栓栓塞症(PTE)发病率和病死率较高,早期诊断和治疗是改善其预后的关键,但PTE临床表现多样化,缺乏特异性,导致漏诊、误诊情况严重。本文从患者、临床医师、医院三个层面对PTE延迟诊断的发生及原因做一梳理,重点阐述PTE与易混淆疾病(冠心病、肺炎、慢性阻塞性肺疾病)的鉴别思路,以期提高PTE早期诊断率。     

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.     

Epidemiology, risk factors and sequelae of venous thromboembolism

The aim of this review was to discuss the epidemiology, risk factors and sequelae of venous thromboembolism (VTE). VTE has an incidence of 1-2 per 1000 people annually. The risk of VTE increases with age and is highest in Caucasians and African Americans. Combined oral contraceptives (COC), especially the third-generation COCs, have been strongly implicated in VTE. Hospitalized patients, especially patients with underlying malignancy and undergoing surgery, have a host of risk factors for VTE. Thrombophilia can predispose an individual to VTE but indiscriminate testing for thrombophilia in patients presenting with VTE is not indicated. VTE can have serious chronic sequelae in the form of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTPH). The risk of PTS and CTPH is increased with recurrent deep vein thrombosis and pulmonary embolism, respectively. Mortality from VTE can be as high as 21.6% at one year. Patients who had an episode of VTE have a high risk of subsequent VTE and this risk is highest in patients who had a first VTE event associated with malignancy. A good understanding of the epidemiology and risk factors of VTE will enable the treating medical practitioners to identify patients at risk and administer appropriate VTE prophylaxis to prevent the long-term consequences of VTE.     

Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism

STUDY OBJECTIVES: To investigate whether the FII A(20210) mutation is associated with isolated pulmonary embolism (PE). DESIGN: Case-control study. SETTING: Five thrombosis centers in southern Italy. PATIENTS: Six hundred forty-seven consecutive referred patients with objectively documented venous thrombosis and 1,329 control subjects. Measurements and results: Medical histories were collected. The G-to-A transition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to-A transition at nucleotide position 20210 within the prothrombin gene locus (FII A(20210)), levels of anticoagulant factors, and levels of antiphospholipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with additional PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% and 16.6%, respectively) and FII A(20210) mutation (14.2% and 12.6%, respectively), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, respectively). In both groups, the frequencies of FV Leiden and/or FII A(20210) mutation were higher than those observed among 1,329 apparently healthy control subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients with isolated PE (n = 126), prevalences of FV Leiden (7.1%) and FII A(20210) mutation (8.7%) were similar to those of control subjects. Inherited thrombophilic abnormalities were less frequent among patients with PE only (15.6%) than among those with DVT only (37.0%; p < 0.001) or whose conditions were complicated by PE (28. 0%; p = 0.020). Adjusting for age and sex, FV Leiden mutation, FII A(20210) mutation, or both mutations were associated with DVT with PE (FV Leiden mutation: odds ratio [OR], 3.0; 95% confidence interval [CI], 1.6 to 5.5; FII A(20210) mutation: OR, 2.6; 95% CI, 1. 3 to 5.2; and both mutations: OR, 82.1; 95% CI, 7.5 to 901.2) or without PE (FV Leiden mutation: OR, 6.1; 95% CI, 4.0 to 9.3; FII A(20210) mutation: OR, 2.8; 95% CI, 1.7 to 4.8; and both mutations: OR, 167.5; 95% CI, 21.6 to 1,297.7), but not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FII A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 22.1; 95% CI, 1. 3 to 370.2). CONCLUSIONS: FII A(20210) mutation is associated with DVT in the lower extremities alone or when complicated by PE, but it is not associated with isolated PE.     

Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology

BACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies. METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998. RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95% CI, 1.0-2.1]). CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.     

非高危急性肺血栓栓塞症相关危险因素及临床指标分析

目的 探讨非高危急性肺血栓栓塞症(简称肺栓塞)的危险因素及临床指标分析.方法 回顾性分析2010年1月～ 2012年1月我院收治的95例急性肺栓塞患者的临床资料,其中低危组37例,中危组58例.应用Logistic回归模型分析中危肺栓塞的独立相关因素.结果 中危组患者呼吸困难、心慌、D-二聚体、心率、SⅠQⅢTⅢ、V1～4导联T波倒置以及CT检查示解剖学大范围肺栓塞均明显高于低危组(P均＜0.01);中危组患者胸痛、血气分析PaO2水平均低于低危组.应用Logistic回归分析确定中危肺栓塞的独立相关因素包括CT检查示解剖学大范围肺栓塞、就诊时心率快以及就诊时高水平D-二聚体.结论 与低危组相比,CT提示解剖学大范围肺栓塞、就诊时心率快以及就诊时高水平D-二聚体与中危肺栓塞的独立相关.