Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy

BACKGROUND: In patients with venous thromboembolism (VTE), identifying clinical risk factors for recurrence during the initial 3 months of anticoagulant therapy and knowledge of the time course of recurrence may help clinicians decide about the frequency of clinical surveillance and the appropriateness of outpatient treatment. METHODS: Analysis of a randomized controlled trial database involving 1021 patients with VTE (750 with deep vein thrombosis [DVT] and 271 with pulmonary embolism [PE]) who were followed up for 3 months after the start of anticoagulant therapy. All patients received initial treatment with unfractionated heparin or a low-molecular-weight heparin (reviparin) and a coumarin derivative starting the first or second day of treatment, with a target international normalized ratio of 2.0 to 3.0. RESULTS: Four independent clinical risk factors for recurrent VTE were identified: (1) cancer (odds ratio [OR], 2.72; 95% confidence interval [CI], 1. 39-5.32), (2) chronic cardiovascular disease (OR, 2.27; 95% CI, 1. 08-4.97), (3) chronic respiratory disease (OR, 1.91; 95% CI, 0.85-4. 26), and (4) other clinically significant medical disease (OR, 1.79; 95% CI, 1.00-3.21). Older age was associated with a decreased risk for recurrent VTE (OR, 0.76; 95% CI, 0.64-0.92). Previous VTE, sex, and idiopathic VTE were not risk factors for recurrence. In patients with DVT or PE, there was no significant difference in the rates of recurrent nonfatal VTE (4.8% vs 4.1%; P =.62), major bleeding (2.9% vs 2.2%; P =.53), and non-VTE death (6.4% vs 7.8%; P =.45), but recurrent fatal PE was more frequent in patients with PE than DVT (2. 2% vs 0%; P<.01). There was a clustering of recurrent VTE episodes during the initial 2 to 3 weeks after the start of treatment. CONCLUSIONS: During the initial 3 months of anticoagulant therapy, recurrent VTE is more likely to occur in patients with cancer, chronic cardiovascular disease, chronic respiratory disease, or other clinically significant medical disease. Patients with PE are as likely to develop recurrent VTE as those with DVT; however, recurrence is more likely to be fatal in patients who initially present with PE. Arch Intern Med. 2000;160:3431-3436.     

Low-molecular-weight and unfractionated heparin for prevention of venous thromboembolism in neurosurgery: a meta-analysis

BACKGROUND: Venous thromboembolism is a common, life-threatening complication in neurosurgery, but prophylaxis with anticoagulant agents has not gained wide acceptance because of concern about intracranial bleeding. We performed a meta-analysis of controlled randomized trials on the efficacy and safety of heparin in the prophylaxis of venous thromboembolism in neurosurgery. OBJECTIVE: To review the clinical benefit of prophylaxis of venous thromboembolism with heparin in the controversial setting of neurosurgery. METHODS: Relevant trials evaluating heparin for prophylaxis of venous thromboembolism in neurosurgery were identified by a MEDLINE search, scan of meeting abstracts, and scrutiny of the references of original articles and reviews. Four controlled randomized studies, 3 of which involved low-molecular-weight heparin, were included in the analysis, and 4 uncontrolled studies are commented on in the article. The outcome measure (observed minus expected number of events) and its variance were calculated for each single trial and then summed. Two-tailed P values and 95% confidence intervals (CIs) were calculated. Efficacy was assessed per protocol and safety by intention-to-treat analysis. The homogeneity of the studies was tested with the chi(2) statistic. The results were also expressed as number needed for 1 extra event. RESULTS: A total of 187 thromboembolic events were recorded in 827 patients (22.6%). Heparin prophylaxis resulted in a 45% relative risk reduction of venous thromboembolic events (odds ratio [OR], 0.48; 95% CI, 0.35-0.66; P<. 001). Nineteen major bleedings were recorded in 1022 patients. None were fatal. Heparin treatment resulted in a 71% relative risk increase of major bleeding (OR, 1.72; 95% CI, 0.69-4.27; P =.24). The number needed to treat was 7.7 for venous thromboembolism and 16 for proximal deep vein thrombosis. The number needed to harm was 102 (115 for low-molecular-weight heparin). CONCLUSIONS: Low-molecular-weight and unfractionated heparin have been shown to be effective for prophylaxis of venous thromboembolism in elective neurosurgery without excessive bleeding risk.     

Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?

PURPOSE: To determine if the location of deep vein thrombosis is a predictor of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy.METHODS: The study population consisted of 1,149 consecutive patients with symptomatic proximal deep vein thrombosis. In all patients, deep vein thrombosis was confirmed by Duplex ultrasound or venography and was classified as popliteal, femoral, or iliofemoral. Patients received initial treatment with unfractionated heparin, enoxaparin, or reviparin for least 4 days, as well as a coumarin derivative, with a target international normalized ratio of 2.0 to 3.0, starting on the 1st or 2nd day of treatment. All patients were followed for 3 months, and all episodes of recurrent venous thromboembolism were confirmed with objective diagnostic tests.RESULTS: The overall rate of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy was 5.5% (63/1,149). The rate of recurrence in patients with popliteal vein thrombosis was 5.1% (23/453); in patients with femoral vein thrombosis, it was 5.3% (34/645); and in patients with iliofemoral vein thrombosis, it was 11.8% (6/51). Two clinical risk factors were associated with an increased risk of recurrent venous thromboembolism: iliofemoral vein thrombosis (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 0.95, 5.9), and cancer (OR = 2.6; 95% CI: 1.5, 4.4).CONCLUSIONS: Patients with extensive iliofemoral vein thrombosis who receive conventional anticoagulant therapy have a greater than twofold higher risk of developing recurrent venous thromboembolism than patients without iliac vein involvement (i.e., 11.8% vs. 5.2%). Prospective studies are needed to determine whether alternative antithrombotic strategies are warranted in such patients.     

Effectiveness and Safety of Rivaroxaban Versus Warfarin in Frail Patients with Venous Thromboembolism

Purpose

Frailty predicts poorer outcomes in patients receiving anticoagulation. We assessed the effectiveness and safety of rivaroxaban vs warfarin in frail patients experiencing venous thromboembolism.

Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism

In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied proportion of included cancer patients (6% to 22.7%) on the incidence of outcome events (recurrence of venous thromboembolism, bleeding, and mortality) and on the estimated treatment effect. Low molecular weight heparin has been extensively investigated in patients with deep vein thrombosis, but few trials have included patients with pulmonary embolism. The risk of recurrence of venous thromboembolism (odds ratio, 0.77; 95% CI, 0.56-1.04), major bleeding (odds ratio, 0.60; 95% CI, 0.38-0.95), and mortality (odds ratio, 0.72; 95% CI, 0.55-0.96) was less with low molecular weight heparins compared with unfractionated heparin. The proportion of cancer patients in these studies had a statistically significant effect on the incidence of recurrent venous thromboembolism (P = 0.03) and mortality (P = 0.002), but no influence on the estimated treatment effects of low molecular weight heparins. Low molecular weight heparin is effective and safe in the initial treatment of venous thromboembolism.     

Heparin and low-molecular-weight heparin therapy for venous thromboembolism. The twilight of anticoagulant monitoring.

Recent improvements in the methods of clinical trials and the use of accurate objective tests to detect venous thromboembolism have made possible a series of randomized trials to evaluate various treatments for venous thromboembolism. The results of these trials have resolved many of the uncertainties a clinician confronts in selecting an appropriate course of anticoagulant therapy. These trials have shown that the intensity of both initial heparin treatment and long-term anticoagulant therapy must be sufficient to prevent unacceptable rates of recurrence of venous thromboembolism. Patients with proximal deep vein thrombosis who receive inadequate anticoagulant therapy have a risk of clinically evident, objectively documented recurrent venous thromboembolism that approaches 20% to 25%. The need for therapy with heparin and the importance of monitoring blood levels of the effect of heparin have been established. The importance of achieving adequate heparinization was suggested by a nonrandomized trial in 1972 and randomized trials in the 1980s have confirmed this finding. Furthermore, randomized trials have demonstrated the importance of achieving adequate heparinization early in the course of therapy. Unfractionated intravenous heparin has provided an effective therapy for more than half a century, but the need to monitor therapy and establish therapeutic levels is a fundamental problem. It is evident that validated heparin protocols are more successful in establishing adequate heparinization than intuitive ordering by the clinician. However, even with the best of care using a heparin protocol, some patients treated with intravenous heparin will receive subtherapy. In this context, subtherapy reflects a practical limitation of the use of unfractionated heparin, rather than a poor standard of care. Furthermore, it is recognized that the practical difficulties associated with heparin administration are compounded by the substantive practical difficulties of standardizing APTT testing and the therapeutic range. Our findings emphasize the confounding effect that initial heparin treatment has on long-term outcome. In future trials of longterm therapy, it is imperative that the initial therapy is of adequate intensity and duration; failure to administer adequate initial treatment may lead to a poor outcome that is falsely attributed to the long-term therapy under evaluation. Therapy with low-molecular-weight heparin, which does not require monitoring and dose finding, is the likely practical solution to these dilemmas. Based on the experience of difficulties achieving adequate therapy with subcutaneous unfractionated heparin dosing, we administered a low-molecular-weight heparin formulation in a single daily dose, rather than splitting the treatment into 2 equal doses. The initial intensity of therapy was thereby maximized. Therapy with low-molecular-weight heparin proved to be better than therapy with unfractionated heparin.     

Dual versus triple antithrombotic therapy in patients undergoing percutaneous coronary intervention-meta-analysis and meta-regression

BackgroundAnti-thrombotic regimen in patients on long term anticoagulation requiring coronary intervention remains a clinical challenge.MethodsWe performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (P2Y12 inhibitor and anticoagulant) in patients on long-term anticoagulants after percutaneous coronary intervention (PCI). Major bleeding was the primary outcome.ResultsThree observational studies and 3 randomized controlled trials with a total of 6654 patients met our selection criteria. At a mean follow up of 12.5 months major bleeding was lower in dual therapy cohort compared to triple therapy (2.2% vs 5.2%, RR 0.60, 95% CI 0.44–0.81, P = 0.001). No difference was observed between the two groups for major adverse cardiac events (11.8% vs 13.0%, RR 1.03, CI 0.79–1.34, P = 0.85), all-cause mortality (3.9% vs 5.6%, RR 0.94, CI 0.65–1.36, P = 0.76), myocardial infarction (3.7% vs 3.9%, RR 1.12, CI 0.83–1.50, P = 0.47), target vessel revascularization (6.8% vs 7.1%, RR 1.12, CI 0.72–1.74, P = 0.60), thromboembolic events (1.3% vs 1.6%, RR 0.95, CI 0.55–1.64, P = 0.85) and stent thrombosis (1.3% vs 1.4%, RR1.36, CI 0.84–2.21, P = 0.21).ConclusionFor patients undergoing PCI and requiring long term anticoagulation, a strategy of P2Y12 inhibitor plus anticoagulant confers a benefit of less major bleeding with no difference in major adverse cardiac events, mortality, myocardial infarction, target vessel revascularization, stent thrombosis or thromboembolism compared with triple therapy.     

Heparin therapy for venous thrombosis and pulmonary embolism

Intravenous heparin is the initial treatment of choice for most patients with acute pulmonary embolism or proximal deep vein thrombosis. The primary objective of initial heparin therapy in such patients is to prevent recurrent venous thromboembolism. The efficacy of intravenous heparin for this purpose has been established by randomized clinical trials in patients with pulmonary embolism, and more recently, in patients with proximal vein thrombosis. Heparin is given as an initial intravenous bolus of 5000 units, followed by a maintenance dose of 30,000-40,000 units per 24 h by continuous intravenous infusion. A recent randomized trial in patients with proximal vein thrombosis indicates that failure to achieve an adequate anticoagulant response (APTT greater than 1.5 times control) is associated with a high risk (25%) of recurrent venous thromboembolism. Intravenous heparin administered in doses that prolong the activated partial thromboplastin time (APTT) to 1.5 or more times the control value is highly effective, and associated with a low frequency (2%) of recurrent venous thromboembolism. Heparin is continued for 7-10 days, overlapped with warfarin sodium during the last 4-5 days. Multiple randomized clinical trials indicate that this approach is highly effective. An alternative approach is to commence heparin and oral anticoagulants together at the time of diagnosis, and to discontinue heparin on the fourth or fifth day. A recent randomized trial in patients with submassive venous thrombosis or pulmonary embolism suggests that 4-5 days of initial heparin therapy is effective and safe, but this approach must be evaluated by further randomized trials before it is recommended for patients with extensive proximal vein thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study

BACKGROUND: The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate. OBJECTIVE: To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism. METHODS: In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer. MAIN OUTCOME MEASURE: A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months. RESULTS: Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P =.09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P =.07). No difference was observed regarding the progression of the underlying cancer or cancer-related death. CONCLUSIONS: These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.     

Noninvasive diagnosis of deep vein thrombosis in postoperative patients

The accuracy of noninvasive testing for the diagnosis of deep vein thrombosis (DVT) generally is less in asymptomatic patients than it is in those with symptoms suggestive of thrombosis. This is because asymptomatic DVT often is confined to the distal veins and, when it involves the proximal veins, the thrombi usually are smaller than in symptomatic patients with proximal thrombosis. Because the positive predictive value of noninvasive tests for asymptomatic DVT generally is 80% or less, abnormal results should be confirmed by venography. There are two main reasons why asymptomatic DVT is sought in the postoperative period: (1) to identify the need for full-dose anticoagulant therapy to prevent symptomatic episodes of venous thromboembolism (VTE), including fatal pulmonary embolism (this represents a form of secondary prophylaxis), and (2) to use this outcome as a surrogate for episodes of clinically important VTE in studies that are designed to evaluate methods of venous thrombosis prophylaxis. In relation to the first of these indications, evidence suggests that routine surveillance of high-risk patients to detect asymptomatic postoperative DVT does not result in improved clinical outcomes in patients who received appropriate VTE prophylaxis. In relation to the second indication, there is concern that asymptomatic VTE may not be a reliable surrogate for clinically important VTE, particularly if the effectiveness of different antithrombotic agents is being compared. Coupled with the comparatively low accuracy of noninvasive testing for asymptomatic DVT, this suggests that the results of such testing are unsuitable for the evaluation of new methods of prophylaxis in clinical trials.     

Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants?

PURPOSES: To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs for patients treated with long-term low-molecular-weight heparin (LMWH) or oral anticoagulant therapy (OAT). METHODS: All randomized studies were searched through computerized queries of MEDLINE, the Cochrane Controlled Trials Register, the American Society of Hematology abstract database, and the American Society of Clinical Oncology abstract database. RESULTS: Eleven studies including 2,907 patients were identified. Seven studies evaluated a period of 3 to 9 months after cessation of the allocated treatment: 5.4% of patients in the LMWH group vs 4% in the arm allocated to OAT had an episode of recurrent symptomatic VTE. Combined analysis showed a nonsignificant trend in lowering recurrent symptomatic VTE in favor of OAT (relative risk [RR], 1.29; 95% confidence interval [CI], 0.82 to 2.02; p = 0.27). By contrast, during active treatment, a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT was registered (RR, 0.63; 95% CI, 0.47 to 0.83; p = 0.001). Regarding cancer patients only, 37 of 569 patients (6.5%) in the LMWH group had recurrent symptomatic VTE vs 69 of 546 patients (12.6%) in the OAT group, with a statistically significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH (RR, 0.52; 95% CI, 0.35 to 0.76; p = 0.001). CONCLUSIONS: Despite the significant reduction of the risk of recurrent symptomatic VTE in favor of LMWH over OAT during treatment, patients treated with long-term LMWH do not seem to have more frequently recurrent VTE events compared with OAT after cessation of therapy. The significant difference favoring LMWH over OAT among all patients receiving treatment comes mostly from studies enrolling cancer patients.     

Reduction in thrombus extension and clinical end points in patients after initial treatment for deep vein thrombosis with the fixed-dose body weight-independent low molecular weight heparin certoparin.

Low molecular weight heparin (LMWH) is effective in the treatment of acute deep vein thrombosis (DVT) in adults. This has not been demonstrated for one LMWH alone. The relationship between venographic changes due to LMWH therapy and clinical outcome in the initial treatment period has not been reported. A pooled analysis of two clinical trials was performed. The trials compared a fixed-dose, body weight-independent, subcutaneous LMWH, certoparin (8000 antifactor Xa [aXa] U twice a day [b.i.d.]), with an adjusted-dose intravenous unfractionated heparin (UFH) with respect to venographic changes expressed as Marder score and occurrence of recurrent venous thromboembolism, major bleeding, and mortality. The Marder score was 23.2 +/- 8.4 in patients randomized to LMWH (n = 299 paired phlebograms) and 23.9 +/- 8.9 in patients allocated to UFH (n = 297 paired phlebograms) at entry (2p = 0.23) and 18.9 +/- 9.7 and 20.5 +/- 9.9 at the end of the initial therapy (2p = 0.04), respectively. The composite outcome of recurrent venous thromboembolism, major bleeding, and mortality occurred less frequently during treatment with LMWH (n = 393) than it did with UFH (n = 404, 1.3% versus 5.0%, risk reduction [RR] 0.26, 95% confidence interval [CI] 0.11 to 0.63, 2p = 0.004). Single events of recurrent thromboembolism (2p = 0.12), major bleeding (2p = 0.03), and mortality (2p = 0.12) were observed less frequently with LMWH. A trend toward a lack of regression of thrombus size was observed in recurrent venous thromboembolism (2p = 0.08). Body weight-independent LMWH significantly reduces thrombus size and the incidence of composite outcome during the initial treatment of acute proximal venous thrombosis compared with adjusted dose intravenous UFH. The data indicate a relation between an unimproved Marder score and a recurrent venous thromboembolism.     

Risk of thromboembolism with short-term interruption of warfarin therapy

BACKGROUND: Significant uncertainty surrounds the treatment of patients who must discontinue warfarin sodium therapy before an invasive procedure. In part, the uncertainty results from the lack of published information about the risk of thromboembolism associated with short-term warfarin therapy interruption. We aimed to assess the frequency of thromboembolism and bleeding within a large cohort of patients whose warfarin therapy was temporarily withheld for an outpatient invasive procedure. METHODS: This prospective, observational cohort study was performed at 101 sites (primarily community-based physician office practices) in the United States. Enrollment was conducted from April 4, 2000, to March 6, 2002. The main outcome measures were thromboembolism or clinically significant hemorrhage within 30 days of warfarin therapy interruption. RESULTS: A total of 1293 episodes of warfarin therapy interruption in 1024 individuals were included. The mean (SD) patient age was 71.9 (10.6) years; 438 (42.8%) were female. The most common indications for anticoagulant therapy were atrial fibrillation (n=550), venous thromboembolism (n=144), and mechanical heart valve (n=132). The most common procedures were colonoscopy and oral and ophthalmic surgery. Perioperative heparin or low-molecular-weight heparin was used in only 8.3% of cases overall. Seven patients (0.7%; 95% confidence interval [CI], 0.3%-1.4%) experienced postprocedure thromboembolism within 30 days. None of the 7 patients who experienced thromboembolism received periprocedural bridging therapy. Six patients (0.6%; 95% CI, 0.2%-1.3%) experienced major bleeding, whereas an additional 17 patients (1.7%; 95% CI, 1.0%-2.6%) experienced a clinically significant, nonmajor bleeding episode. Of these 23 patients who had bleeding episodes, 14 received periprocedural heparin or low-molecular-weight heparin. The duration of warfarin therapy interruption was variable; however, more than 80% of patients had warfarin therapy withheld for 5 days or fewer. CONCLUSIONS: For many patients receiving long-term anticoagulation who need to undergo a minor outpatient intervention, a brief (< or =5 days) periprocedural interruption of warfarin therapy is associated with a low risk of thromboembolism. The risk of clinically significant bleeding, even among outpatients undergoing minor procedures, should be weighed against the thromboembolic risk of an individual patient before the administration of bridging anticoagulant therapy.     

Evaluating the efficacy and safety of apixaban, a new oral anticoagulant, using Bayesian meta-analysis

Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. This study sought to evaluate the efficacy and safety of apixaban versus enoxaparin. A systematic search of the literature for randomized controlled trials of apixaban thromboprophylaxis versus enoxaparin was conducted using three databases: PubMed, EMBASE, and the Cochrane library. Five studies that included a total of 12,938 patients were analyzed using Bayesian random-effects meta-analysis. To evaluate efficacy, a composite of venous thromboembolism and death during follow-up was measured. To evaluate safety, major and total bleeding events were considered. The odds ratio (OR) for the composite outcome of efficacy was 0.66 (95 % CI 0.33–1.29) for apixaban compared to enoxaparin, while there was a similar risk of major bleeding (OR 1.03, 95 % CI 0.36–3.73) and total bleeding (OR 0.92, 95 % CI 0.64–1.20). These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.     

急性肺血栓栓塞症患者溶栓治疗后的远期预后分析

目的　分析急性大面积肺血栓栓塞症 (PTE)患者溶栓治疗后的远期预后。方法　对2 60例急性PTE患者进行溶栓治疗并随访 ,分析其临床资料及引起远期临床事件 [死亡、再发深静脉血栓形成、再发PTE、慢性血栓栓塞性肺动脉高压和 (或 )右心衰竭、抗凝治疗出现大出血、依赖家庭氧疗 ]的危险因素。结果　 2 60例PTE患者在住院期间死亡 2 2例 (8 5 % ) ,其中 1 5例 (62 8% )死于PTE。随访 2 2 7例患者 ,为期 3 9～ 8 4年 ,死亡 72例 (31 7% ) ,其中有 2 1例患者死于再发PTE。对随访资料完整的 1 65例患者进行远期临床事件的危险因素分析 ,单因素分析显示 ,既往有血栓栓塞病史、抗凝治疗不足 6个月、植入下腔静脉滤器、溶栓后超声心动图仍显示右室功能障碍和 (或 )扩大、溶栓后超声多普勒仍测得肺动脉收缩压 >50mmHg、出院前核素肺通气 /灌注扫描显示肺血管床阻塞 >30 %与远期临床事件的发生相关 ;多变量分析显示 ,溶栓后超声心动图仍显示右室功能障碍和 (或 )扩大、溶栓后超声多普勒仍测得肺动脉收缩压 >50mmHg、出院前核素肺通气 /灌注扫描显示肺血管床阻塞 >30 %是PTE远期预后的独立危险因素。结论　通过高危因素的确立 ,可予患者更积极的治疗 ,改善患者的预后     

Low-molecular-weight heparin for the treatment of venous thromboembolism in the elderly.

Venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) is a common problem in the elderly population. Indeed, increasing age is a significant risk factor for venous thromboembolism. The treatment of venous thromboembolism in the elderly population presents certain unique problems related to aging, such as decreasing body weight, increasing renal insufficiency and numerous comorbid conditions, which complicate therapy. Treatment of venous thromboembolism in the elderly has been complicated by an increased incidence of bleeding, particularly with the use of warfarin. The risk of bleeding may be substantially reduced by carefully adjusting the warfarin dose to maintain a therapeutic INR and for this purpose anticoagulant management clinics have been shown to be useful. The low-molecular-weight heparins have been shown to be efficacious and safe for the treatment of venous thromboembolism in several clinical trials, including many patients in the older age brackets. Furthermore, these agents can safely be used in the out-of-hospital setting. Long-term use of low-molecular-weight heparin is an alternative to the use of oral anticoagulant therapy, particularly in patients with cancer or recurrent venous thromboembolism.     

Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis

A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included patients, 181 had known cancer at entry. The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7% (95% CI, 15.6%-25.8%) versus 6.8% (95% CI, 3.9%- 9.7%) in patients without cancer, for a hazard ratio of 3.2 (95% CI, 1.9-5.4) The 12-month cumulative incidence of major bleeding was 12.4% (95% CI, 6.5%-18.2%) in patients with cancer and 4.9% (95% CI, 2.5%-7.4%) in patients without cancer, for a hazard ratio of 2.2 (95% CI, 1.2-4.1). Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation. Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy. These risks correlate with the extent of cancer. Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed.     

Gemcitabine-based combination therapy com-pared with gemcitabine alone for advanced pancreatic cancer: a meta-analysis of nine randomized controlled trials

BACKGROUND: Pancreatic cancer is one of the most aggres-sive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine (GEM) is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer.DATA SOURCES: A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Co-chrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival (OS), 6-month survival, 1-year survival, progression-free survival/time-to-progression (PFS/TTP), and toxicities.RESULTS: A total of nine randomized controlled trials involv-ing 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS (HR=0.85, 95% CI: 0.76-0.95, P=0.003), PFS (HR=0.76, 95% CI: 0.65-0.90, P=0.002), 6-month survival (RR=1.09, 95% CI: 1.01-1.17, P=0.03), and the overall toxicity (RR=1.68, 95% CI: 1.52-1.86, P<0.01). However, there was no significant difference in the 1-year survival.CONCLUSIONS: GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pan-creatic cancer. However, combined therapy also added toxicity.     

Treatment of deep vein thrombosis

Most patients who present with deep vein thrombosis (DVT) can be treated with weight-adjusted, fixed-dose, low molecular heparin as an outpatient. The subsequent duration of oral anticoagulant therapy should be individualized according to the risk of recurrent venous thromboembolism and the risk of anticoagulant-induced bleeding. The risk of recurrence is low if thrombosis was provoked by a major reversible risk factor such as surgery; 3 months of treatment is usually adequate for such patients. The risk of recurrence is high if thrombosis was unprovoked ("idiopathic") or associated with a nonreversible risk factor such as active cancer; at least 6 months, and sometimes indefinite, anticoagulant therapy is indicated for such patients. The presence of an antiphospholipid antibody, and other selected thrombophilic states, favors more prolonged therapy within each of the categories noted previously. Systemic thrombolytic therapy helps to restore venous patency and probably reduces the risk of the postthrombotic syndrome; however, it is associated with an unacceptable risk of bleeding. Catheter-directed thromboylsis, particularly for isolated iliofemoral thrombosis, may be beneficial and needs further evaluation in controlled trials.     

Vitamin K Antagonists After 6 Months of Low-Molecular-Weight Heparin in Cancer Patients with Venous Thromboembolism

Background

Low-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond 6 months remain scanty.