Acquired risk factors for venous thromboembolism in medical patients.
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Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder, which often complicates the course of hospitalized patients, but may also affect ambulatory and otherwise healthy people. While the introduction of thromboprophylactic measures is expected to have reduced the occurrence of postoperative VTE, there is an increasing awareness of the importance of medical conditions in determining thromboembolic events. Among the conditions that predispose patients to VTE are increasing age, cancer and its treatment, prolonged immobility, stroke or paralysis, previous VTE, congestive heart failure, acute infection, pregnancy or puerperium, dehydration, hormonal treatment, varicose veins, long air travel, acute inflammatory bowel disease, rheumatologic disease, and nephrotic syndrome. Other factors that have recently been associated with an increased risk of VTE disorders include persistent elevation of D-dimer and atherosclerotic disease. Recognition of the incidence and clinical importance of thrombosis will most likely encourage more widespread use of antithrombotic prophylaxis in medical patients. (+info)
Thrombosis and the antiphospholipid syndrome.
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The antiphospholipid syndrome is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. Several studies have determined that the frequency of antiphospholipid syndrome in patients presenting with a venous thromboembolic event is between 4% and 14%. Because of the high risk for recurrent thromboembolism in these patients, current recommendations suggest a longer, potentially lifelong, course of antithrombotic therapy following an initial event. Although most authorities agree on an extended course of therapy, considerable controversy surrounds the optimal target therapeutic INR for patients with antiphospholipid syndrome. For an initial venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two prospective, randomized clinical trials. In contrast, relatively limited data exist for an initial arterial thromboembolic event in patients who have the antiphospholipid syndrome, and therapeutic recommendations range from aspirin to warfarin with a high target INR. Recurrent thromboembolic events can be extremely difficult to treat, and some patients may benefit from the addition of immunosuppressive therapies. Importantly, as many as 50% of the initial thromboembolic events sustained by patients with antiphospholipid antibodies occur in the setting of additional, coincident prothrombotic risk factors, indicating the importance of addressing any additional risk factors, such as hypercholesterolemia, in these patients. Prospective studies are needed to address the role of thromboprophylactic strategies in asymptomatic individuals with antiphospholipid antibodies in the absence of additional risk factors. (+info)
Prophylaxis of venous thrombosis in medical patients: A real-world perspective.
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BACKGROUND: Although low-molecular weight heparins (LMWH) have been proven to be efficacious for prophylaxis of venous thrombo-embolism (VTE) in non-surgical patients, their use and safety outside the setting of a clinical trial has not been investigated. OBJECTIVE: The objective of this survey was to determine the efficacy and safety of LMWH (enoxaparin) in the prevention of VTE in a study population comprising general medical patients. METHODS: The study involved an open-label, non-controlled, multicentre survey of any patient confined to bed due to medical illness, where the physician had made an independent decision to prescribe LMWH as prophylaxis for VTE. The demographic information and risk factors for venous thrombosis and dose of enoxaparin were recorded. Patients were assessed for clinical evidence of VTE. Only if this was present were further invasive investigations performed. Adverse events relating to the use of LMWH were recorded. RESULTS: Four hundred and seventy-one patients were enrolled from 53 centres. Five per cent of the patients were treated for up to and including three days, 4.4% for four days or less, 49.6% for six days or less, and a further 45.5 % for seven to 21 days. The most frequently prescribed dose was enoxaparin 40 mg once daily (86%). Of the enrolled patients, 28.2% had one risk factor and 69.8% had two or more risk factors for the development of VTE. The incidence of clinically suspected deep-vein thrombosis (DVT) or pulmonary embolism (PE) in this survey was three out of 457 patients at risk, ie, 0.66%. One serious adverse event occurred in an incorrectly enrolled surgical patient and 22 minor adverse events occurred that were thought by the enrolling physician to be related to the study drug. CONCLUSION: This survey was not designed to test for efficacy in DVT prevention. However the incidence of clinically identified DVT was low and there were no deaths from PE. This probably represents a considerable reduction in morbidity and mortality from that described in studies comparing LMWH with placebo. Enoxaparin may be used with confidence in a 'real-world' situation out of the confines of a study in which exclusions, inclusions and therapy are rigorously controlled. (+info)
The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study.
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INTRODUCTION: The alpha-fibrinogen Thr312Ala variant has been shown to influence clot structure through increased factor XIII cross-linking and formation of thicker fibrin fibers. However, the effect of this common variant on risk of venous thromboembolism (VTE) is unclear. This paper reports the association between the Thr312Ala variant and VTE in the LITE study. MATERIALS AND METHODS: 506 cases and 1014 controls frequency matched on age, sex, race, and study were drawn from two prospective studies and included in the analysis. Logistic regression was used to examine the association between Thr312Ala and VTE. RESULTS: In a logistic regression model minimally adjusted for the matching variables, the Thr312Ala TA and AA genotypes were associated with a significantly higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27 [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE and DVT considered separately and across racial and study subgroups. The association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected by an additive or multiplicative model of individual risk factors. CONCLUSIONS: These results suggest that alpha-fibrinogen Thr312Ala is involved in the pathogenesis of VTE and that its action may be modified by other VTE risk factors. (+info)
Fondaparinux prevents venous thromboembolism after joint replacement surgery in Japanese patients.
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Venous thromboembolism (VTE) is an important complication of major orthopaedic surgery of the lower limbs. Fondaparinux, a synthetic pentasaccharide and highly selective inhibitor of activated Factor Xa, is the first in a new class of antithrombotic agents. To determine the optimal dose in Japanese patients, double-blind, placebo-controlled, dose-ranging studies of fondaparinux were conducted in patients undergoing total knee replacement (TKR) or total hip replacement (THR) surgery. Patients were randomly assigned to receive a once-daily subcutaneous injection of fondaparinux (0.75, 1.5, 2.5, or 3.0 mg) or placebo in Study 1 (TKR) and Study 2 (THR). In Study 1, the incidence of VTE was 65.3% in the placebo group and was 34.2%, 21.3%, 16.2%, and 9.5% in the groups receiving 0.75, 1.5, 2.5, and 3.0 mg fondaparinux respectively. In Study 2, the incidence of VTE was 33.8% in the placebo group and was 24.2%, 4.6%, 7.4%, and 14.4% in the 0.75, 1.5, 2.5, and 3.0 mg fondaparinux groups respectively. Dose-response effects were observed in both studies; however, no statistically significant differences in major bleeding events were found among any groups. Fondaparinux proved to be a potent anticoagulant with a favourable benefit-to-risk ratio in the prevention of VTE in these study patients. (+info)
Detection of venous thromboembolism by proteomic serum biomarkers.
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BACKGROUND: Available blood assays for venous thromboembolism (VTE) suffer from diminished specificity. Compared with single marker tests, such as D-dimer, a multi-marker strategy may improve diagnostic ability. We used direct mass spectrometry (MS) analysis of serum from patients with VTE to determine whether protein expression profiles would predict diagnosis. METHODS AND RESULTS: We developed a direct MS and computational approach to the proteomic analysis of serum. Using this new method, we analyzed serum from inpatients undergoing radiographic evaluation for VTE. In a balanced cohort of 76 patients, a neural network-based prediction model was built using a training subset of the cohort to first identify proteomic patterns of VTE. The proteomic patterns were then validated in a separate group of patients within the cohort. The model yielded a sensitivity of 68% and specificity of 89%, which exceeded the specificity of D-dimer assay tested by latex agglutination, ELISA, and immunoturbimetric methods (sensitivity/specificity of 63.2%/60.5%, 97.4%/21.1%, 97.4%/15.8%, respectively). We validated differences in protein expression between patients with and without VTE using more traditional gel-based analysis of the same serum samples. CONCLUSION: Protein expression analysis of serum using direct MS demonstrates potential diagnostic utility for VTE. This pilot study is the first such direct MS study to be applied to a cardiovascular disease. Differences in protein expression were identified and subsequently validated in a separate group of patients. The findings in this initial cohort can be evaluated in other independent cohorts, including patients with inflammatory conditions and chronic (but not acute) VTE, for the diagnosis of VTE. (+info)
The use of enoxaparin to prevent venous thromboembolism in patients undergoing radical retropubic prostatectomy: feasibility and utility.
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OBJECTIVE: To assess the utility of enoxaparin in prevention of venous thromboembolism (VTE) in men poorly compliant with pneumatic compression stockings (PCS) in the immediate postoperative period after a radical retropubic prostatectomy (RP). MATERIALS AND METHODS: This retrospective study included 47 men who underwent RP at an inner-city tertiary care hospital. All patients were started on enoxaparin 40 mg subcutaneously 6-8 hours postoperatively and daily while hospitalized. Preoperative, operative, and postoperative data were collected and analyzed. Median follow-up was 18 months. RESULTS: Median patient age was 64 +/- 7 years, median prostate-specific antigen level was 4.9 ng/mL and median prostate biopsy-determined Gleason score was 6. Forty-one men (87%) underwent a pelvic lymph node dissection. Median operative time was 181 minutes (range 164-450 minutes). Median estimated blood loss was 700 mL. Approximately 36% of the men wore PCS the recommended > 19 hours/day. On average PCS were worn 10.3 +/- 7.5 hours/day. Postoperative complications were not increased in this cohort. Two patients developed pulmonary embolism requiring long-term anticoagulation. There were no mortalities. CONCLUSIONS: In men non-compliant with PCS, initiation of enoxaparin in the immediate postoperative setting was well-tolerated and maintained a low (4%) rate of VTE. Thus, enoxaparin may be useful in adjunct with PCS in these patients. (+info)
Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.
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BACKGROUND: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis. (+info)