慢性阻塞性肺疾病与凝血-纤溶功能异常

慢性阻塞性肺疾病（COPD）是以气道、肺实质和肺血管的慢性炎症为特征。因肺内通气血流比例失调致慢性缺氧，可继发红细胞增多和血黏滞度增高，引起血流高黏、高聚、高凝及微血栓形成。COPD急性加重期凝血-纤溶功能异常进一步恶化，对病情进展的影响已经为临床高度关注。研究同时发现COPD与静脉血栓栓塞症（VTE）关系密切，其合并深静脉血栓（DVT）甚至肺血栓栓塞症（PTE）已成为重要的医疗保健问题。  

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.  

Low Intensity Warfarin Anticoagulation is Safe and Effective as a Long-Term Venous Thromboembolism Prevention Strategy

Longitudinal studies indicate a high rate of recurrence of venous thromboembolism after an episode of deep venous thrombosis or pulmonary embolism. Extended anticoagulant therapy will decrease the recurrence rate, but there is controversy as to the optimal intensity of therapy that will be effective, yet safe. The PREVENT trial addresses the question of whether long-term low intensity therapy (INR 1.5–2.0) will effectively prevent recurrence compared to placebo treatment, yet be safe without a significant increase in major bleeding. The results of this trial show a significant reduction in recurrent venous thromboembolism with a major bleeding rate that is no different than the placebo arm of the study (0.9 vs 0.4 per 100 patient years; p = 0.25). Although the ELATE trial showed greater effectiveness with no increase in bleeding in the standard intensity arm vs the low intensity arm, the question remains whether such safety can be obtained in the real world management of oral anticoagulation.  

The risk of venous thromboembolism is markedly elevated in patients with diabetes

Aims/hypothesis Diabetes mellitus is associated with several changes in coagulation and fibrinolysis that may lead to a thrombogenic propensity. However, it is not known whether these perturbations actually cause increased risk of venous thromboembolism.Methods In a retrospective population-based study we evaluated the medical records of all 302 adult patients who were admitted to the Umeå University Hospital with verified deep vein thrombosis or pulmonary embolism during the years 1997 to 1999. The patients were classified as diabetic (n=56) and non-diabetic (n=246) according to clinical information. The total number of diagnosed diabetic patients in different age groups in the catchment area was obtained from computerised registries in the primary health care centres and the Umeå University Hospital, and data on the background population were collected from the Swedish population registry.Results The annual incidence rate of venous thromboembolism among diabetic patients in the population was 432 per 100,000 individuals (95% CI 375–496). In non-diabetic individuals it was 78 (95% CI 68–88). The age-adjusted incidence rate among the diabetic population was 274 (95% CI 262–286). The annual incidence rate of venous thromboembolism was elevated in type 1 and type 2 diabetic patients and the incidence rates were 704 (95% CI 314–1,566) and 412 (95% CI 312–544) respectively. The overall standardised morbidity ratio was 2.27 (95% CI 1.75–2.95), i.e. diabetic patients were more prone to venous thromboembolism after adjustment for age differences.Conclusions/interpretation These results suggest that the age-adjusted risk for venous thromboembolism is more than two-fold higher among diabetic patients than in the non-diabetic background population.  

Prevalence and risk of pulmonary embolism in patients with intracardiac thrombosis: a population-based study of 23 796 consecutive autopsies.

AIMS: While right intracardiac thrombosis (IT) is a potential cause of pulmonary embolism (PE) similar to that of stroke in left-sided IT, its prevalence and prognostic significance has not been studied in the general population. The aim of this study was to assess the age- and gender-specific prevalence of IT and its relation to PE in a population-based autopsy cohort. METHODS AND RESULTS: Between 1970 and 1982, 23 796 autopsies, representing 84% of all in-hospital deaths in the Malm? city population, were performed, using a standardized procedure. The relationship between IT and PE was evaluated by cohort analyses and nested case-control studies. IT was present in 1706 (7.2%) patients, 727 and 747 of whom had right and left atrial IT, respectively. PE prevalence in patients with isolated left IT, isolated right IT, and combined IT was 28.5, 35.6, and 48.9%, with RR (95% CI) of 1.5 (1.3-1.8), 2.0 (1.6-2.5), and 3.5 (2.7-4.7), respectively, compared with age- and gender-matched controls. Patients dying from ischaemic heart disease had a 3.2 (2.7-3.6) times higher risk of right IT, which was associated with 43% PE prevalence. Of all patients with PE at autopsy, right IT was found in 354 (6.5%), and the only detected source of PE in 220 (4.0%). CONCLUSION: Right cardiac thrombosis, though difficult to assess clinically, is as common as left cardiac thrombosis and is associated with an increased risk of PE. The diagnosis should be considered in all cases of PE, especially in patients with atrial fibrillation or myocardial infarction and in the absence of confirmed deep vein thrombosis.  

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.  

Factor V Leiden: the venous thrombotic risk in thrombophilic families

Factor V Leiden (FVL) leads to a sevenfold increased risk of venous thrombosis and is present in 50% of individuals from families referred because of unexplained familial thrombophilia. We assessed the association of FVL with venous thromboembolism (VTE) in 12 thrombophilic families of symptomatic probands with FVL in a retrospective follow-up study. We screened 182 first- and second-degree relatives of the 12 unrelated propositi for the FVL mutation and the occurrence of VTE. The incidence rate of VTE in carriers of FVL (0.56%/year) was about six times the incidence for the Dutch population (0.1%/year). The incidence rate in non-carriers also appeared to be higher (0.15% per year). At the age of 50 years, the probability of not being affected by VTE was reduced to 75% for carriers and to 93% for non-carriers (P = 0.009). Identification of carriers of FV Leiden may be worthwhile in young symptomatic individuals and their relatives with a strong positive family history of venous thromboembolism or a history of recurrent venous thrombosis who may be at risk (e.g. pregnancy, use of oral contraceptives). After adjustment for prothrombin G20210A (present in two families), even higher thrombotic incidence rates were found in carriers and non-carriers of FVL. This makes the presence of other unknown prothrombotic risk factors more probable in these families.  

Catheter-directed thrombolysis (intrathrombus injection) in treatment of deep venous thrombosis: a systematic review.

Methods of delivery of thrombolytic agents for massive or limb threatening deep venous thrombosis (DVT) include a systemic infusion, local-regional administration, and catheter-directed therapy (tip of catheter placed inside the thrombus). We evaluated the effectiveness of catheter-directed therapy and compared the results with randomized clinical trials of systemic and local-regional thrombolytic therapy. Many who used catheter-directed thrombolysis used balloon angioplasty, stents, or thrombectomy in addition. Pooled data showed higher rates of complete early opening of occluded veins with catheter-directed thrombolysis alone, 90%, or with catheter-directed thrombolysis often followed by adjunct therapy, 76%, than with a systemic infusion, 28%, or local-regional administration, 20%. The prevalence of postthrombotic syndrome was lower with catheter-directed combined with adjunct therapy, 26%, compared with 56% and 69%, respectively. Rates of any bleeding were higher with catheter-directed thrombolytic therapy, but bleeding was usually minor. In conclusion, the data suggest that catheter-directed thrombolytic therapy may be more beneficial than systemic or local regional administration. An advantage is that it lends itself to adjunct treatment following the administration of thrombolytic agents if the thrombolysis is inadequate.  

The Epidemiology of Venous Thromboembolism in the Community: Implications for Prevention and Management

The epidemiology of venous thromboembolism (VTE) in the community has important implications for VTE prevention and management. This review describes the incidence, survival, recurrence, complications and risk factors for deep vein thrombosis and pulmonary embolism occurring in the community. VTE incidence among whites of European origin exceeds 1 per 1000; the incidence among persons of African and Asian origin may be higher and lower, respectively. VTE incidence over recent time remains unchanged. Survival after VTE is worse than expected, especially for pulmonary embolism where one-quarter of patients present as sudden death. Of those patients who survive, 30% develop VTE recurrence and venous stasis syndrome within 10 and 20 years, respectively. Common independent VTE risk factors include surgery, hospitalization for acute medical illness, nursing home confinement, trauma, active cancer, neurologic disease with extremity paresis, superficial vein thrombosis, central venous catheter/transvenous pacemaker, and among women, oral contraceptives, pregnancy and the puerperium, and hormone and SERM therapy. Exposures can identify populations at risk but have a low predictive value for the individual person. An acquired or familial thrombophilia may predict the subset of exposed persons who actually develop symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs frequently and causes serious long-term complications. To improve survival and prevent complications, VTE occurrence must be reduced. Better individual risk stratification is needed in order to modify exposures and target primary and secondary prophylaxis to the person who would benefit most. Funded, in part, by grants from the National Institutes of Health (HL-60279, HL-66216, AR-30582) and Centers for Disease Control and Prevention (TS-326), U.S. Public Health Service; and by Mayo Foundation