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PubMed2005

Selecting an anticoagulant for recurrent venous thromboembolism in cancer.

PURPOSE: The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population. SUMMARY: The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation. CONCLUSION: Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

Anticoagulants↗
PubMed1998

Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease.

BACKGROUND: Elevated plasma homocysteine (Hcy) levels are implicated in the development of atherosclerotic and venous thromboembolic disease. A meta-analysis of the risk for venous thromboembolism (VTE) in the presence of hyperhomocysteinemia (hyper-Hcy) was performed. METHODS: Studies were identified through MEDLINE (January 1980 to August 1997) using search terms related to both Hcy and VTE. The bibliographies of all review articles and letters were searched for additional relevant articles. English-language studies were selected if they included 10 or more human subjects; a measurement of the plasma, serum, or whole-blood Hcy level; the presence of VTE; and primary data that were not published elsewhere. Seventy-two articles were retrieved, of which 9 met all inclusion criteria. Data were extracted on the study type, subject demographics, methods for matching control subjects with case patients, whether an objective method was used to diagnose VTE, and whether other causes of thrombophilia and elevated Hcy levels were considered. The mean Hcy levels, both in the fasting state and following methionine loading, if done, were recorded, as were the number of patients and control subjects with Hcy levels greater than 2 SDs or greater than the 95th percentile above the mean value of the control group. RESULTS: Nine case-control studies measured fasting plasma Hcy levels, and 5 also measured Hcy values after methionine loading. All 9 studies showed a similar qualitative trend in fasting levels in the associated risk for hyper-Hcy and VTE. The corresponding pooled odds ratio was 2.95 (95% confidence interval, 2.08-4.17; 2-sided P<.001), with no evidence for heterogeneity across the studies (P = .50). Following methionine loading, the trend was also toward increasing the risk of VTE with hyper-Hcy (odds ratio, 2.15; 95% confidence interval, 1.20-3.85; 2-sided P = .01). Again, no evidence of heterogeneity was found (P = .65). The pooled odds ratio for VTE in the presence of hyper-Hcy rose to 4.37 (95% confidence interval, 1.94-9.84) when studies with patients older than 60 years were excluded. Limitations of the individual studies included a lack of proper matching of patients with control subjects, a limited description of subject recruitment, and a failure to test for other hypercoagulable mechanisms and other causes of elevated Hcy levels, such as renal insufficiency or folate deficiency. CONCLUSIONS: A significant risk for VTE in the presence of hyper-Hcy apparently exists among a spectrum of patients with first or recurrent venous thromboembolic events. This risk appears to be most significant for patients with VTE disease before age 60 years. A well-designed prospective study is needed to confirm these findings.

Adolescent↗
PubMed1998

The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Canadian Collaborative Group.

BACKGROUND: Despite low molecular weight heparin prophylaxis, the incidence of venographically detected, residual deep vein thrombosis after hip and knee arthroplasty remains high, at approximately 15% and 30%, respectively. Most of these thrombi are asymptomatic and of unknown clinical significance. Nevertheless, because they have the potential to grow, limiting prophylaxis to the in-hospital period may provide inadequate protection. METHODS: We studied a cohort of 1984 consecutive patients who had hip or knee arthroplasty at 1 of 28 participating hospitals. Patients received enoxaparin prophylaxis, 30 mg subcutaneously every 12 hours for up to 14 days, and underwent predischarge compression ultrasonography. Study end points were symptomatic deep vein thrombosis or pulmonary embolism during and after prophylaxis, asymptomatic venous thrombosis detected by predischarge compression ultrasonography, and major hemorrhage. The duration of follow-up was 84 days. RESULTS: Enoxaparin treatment was started a mean (+/- SD) of 17.9 +/- 10.4 hours after the completion of surgery and was given for a mean of 18.0 +/- 6.9 doses. Eighty-two patients (4.1%; 95% confidence interval, 3.3%-5.0%) developed venous thromboembolism. The rates of thromboembolic events during and after prophylaxis were 2.1% and 2.0%, respectively. Only 3 patients (0.15%) had abnormal predischarge compression ultrasonography. Three patients (0.15%) died of pulmonary embolism. Major hemorrhage occurred in 58 patients (2.9%; 95% confidence interval, 2.2%-3.7%). CONCLUSIONS: Postoperative prophylaxis with enoxaparin for a mean of 9 days is associated with a clinically acceptable rate of symptomatic venous thromboembolism and major hemorrhage. Predischarge compression ultrasonography cannot be justified.

Adult↗
PubMed1999

Economic analysis of low-dose heparin vs the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism after colorectal surgery.

BACKGROUND: Low-dose heparin and low-molecular-weight heparin are effective strategies for preventing venous thromboembolism in colorectal surgery. The economic attractiveness of these 2 strategies in North America is unknown. We conducted an economic analysis of low-dose heparin calcium compared with enoxaparin sodium, a low-molecular-weight heparin, for thromboembolism prophylaxis after colorectal surgery. METHODS: We used decision analysis, with an economic perspective of a third-party payer. Efficacy data were obtained from the Canadian Multicentre Colorectal Deep Vein Thrombosis Prophylaxis Trial and a literature review. Canadian costs for diagnosis and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding were obtained from chart review and a national hospital database of colorectal surgery; American costs were obtained from published literature. The main outcomes were incremental benefits (symptomatic DVTs, symptomatic PEs, and major bleeding events avoided) and incremental costs for every 1000 patients treated. RESULTS: In the Canadian Colorectal Trial, the relative risk of DVT and PE for enoxaparin compared with low-dose heparin was 1.0 (95% confidence interval, 0.7-1.5), and the relative risk of major bleeding was 1.8 (95% confidence interval, 0.8-3.9). With the use of these data in the baseline analysis, a strategy of enoxaparin prophylaxis was associated with equal numbers of symptomatic DVTs and PEs, and an excess of 12 major bleeding episodes for every 1000 patients treated, with an additional cost of $86 050 (Canadian data) or $145 667 (US data). In a sensitivity analysis using optimal assumptions for efficacy and safety of enoxaparin (relative risk of DVT, 0.8; relative risk of PE, 0.4; relative risk of major bleeding, 1.0), a strategy of enoxaparin prophylaxis was associated with 0.8 fewer symptomatic DVT, 3 fewer symptomatic PEs, and equal numbers of major bleeding episodes for every 1000 patients treated, with an additional cost of $15 217 (Canadian data) or $107 614 (US data). CONCLUSION: Although heparin and enoxaparin are equally effective, low-dose heparin is a more economically attractive choice for thromboembolism prophylaxis after colorectal surgery.

Anticoagulants↗
PubMed2000

A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism.

BACKGROUND: There are few population-based data regarding the effectiveness of inferior vena cava filter use in the prevention of symptomatic pulmonary embolism. OBJECTIVE: To determine the 1-year cumulative incidence of rehospitalization for venous thrombosis or pulmonary embolism among patients with thromboembolism treated with a vena cava filter compared with the incidence in a control population with thromboembolism. PATIENTS AND METHODS: Population-based retrospective analysis of linked hospital discharge abstracts in California. From January 1, 1991, through December 30, 1995, 3632 patients were treated with a filter and 64,333 controls were admitted with a principal diagnosis of venous thromboembolism. RESULTS: Filter-treated patients had significantly greater comorbidity, with a higher frequency of previous pulmonary embolism, recent major bleeding, malignant neoplasm, and stroke. Patients who initially manifested pulmonary embolism were significantly more likely to be rehospitalized for pulmonary embolism than patients with an initial diagnosis of venous thrombosis alone, among filter-treated patients (relative risk, 6.72; 95% confidence interval, 3.61-12.49) and controls (relative risk, 5.30; 95% confidence interval, 4.61-6.10). Risk-adjusted proportional hazards modeling showed no significant difference between filter-treated patients and controls in the relative hazard of rehospitalization for pulmonary embolism. However, filter placement was associated with a significantly higher relative hazard of rehospitalization for venous thrombosis among patients who initially manifested pulmonary embolism (relative hazard, 2.62; 95% confidence interval, 2.09-3.29), but not among those who presented with venous thrombosis (relative hazard, 1.14; 95% confidence interval, 0.92-1.43). CONCLUSIONS: Insertion of a vena cava filter was not associated with a significant reduction in the 1-year incidence of rehospitalization for pulmonary embolism. Use of a filter was associated with a higher incidence of rehospitalization for venous thrombosis, but only among patients who initially manifested pulmonary embolism. A prospective clinical study is needed to determine the efficacy of filter use among patients with pulmonary embolism who do not meet strict guidelines for insertion of a vena cava filter.

Adult↗
PubMed2002

Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular-weight heparin with oral anticoagulant.

BACKGROUND: Oral anticoagulants and low-molecular-weight heparin are both recommended for venous thromboembolism prophylaxis after total hip replacement. To date, these regimens have not been compared by means of clinical end points in the extended prophylaxis setting. METHODS: We randomly assigned 1279 patients 3 days after total hip replacement surgery to fixed-dose subcutaneous low-molecular-weight heparin (reviparin sodium, 4200 anti-Xa IU) or adjusted-dose oral anticoagulant (international normalized ratio, 2-3; acenocoumarol) for a 6-week period. The primary end point was the failure rate, defined as the combined clinical events of a confirmed symptomatic thromboembolic event, a major hemorrhage, or death. All patients were followed up throughout the study interval. The primary objective was to compare the observed cumulative failure rate in the low-molecular-weight heparin vs oral anticoagulant group. RESULTS: In the intent-to-treat population, objectively documented symptomatic thromboembolic events occurred in 15 (2.3%) of 643 patients vs 21 (3.3%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.30; 95% confidence interval for the difference, -0.8% to 2.8%). Major bleeding occurred in 9 (1.4%) of 643 patients vs 35 (5.5%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.001). The failure rate was 24 (3.7%) of 643 patients compared with 53 (8.3%) of 636 patients who received low-molecular-weight heparin or oral anticoagulants (P =.001). CONCLUSIONS: A significantly higher benefit-risk ratio was observed for patients undergoing elective hip replacement who received extended out-of-hospital prophylaxis with low-molecular-weight heparin vs acenocoumarol. Low-molecular-weight heparin prophylaxis was at least as effective as oral anticoagulants, but with a marked improvement in safety.

Acenocoumarol↗
PubMed2000

A clinical decision support system for prevention of venous thromboembolism: effect on physician behavior.

CONTEXT: Computer-based clinical decision support systems (CDSSs) have been promoted for their potential to improve quality of health care. However, given the limited range of clinical settings in which they have been tested, such systems must be evaluated rigorously before widespread introduction into clinical practice. OBJECTIVE: To determine whether presentation of venous thromboembolism prophylaxis guidelines using a CDSS increases the proportion of appropriate clinical practice decisions made. DESIGN: Time-series study conducted between December 1997 and July 1999. SETTING: Orthopedic surgery department of a teaching hospital in Paris, France. PARTICIPANTS: A total of 1971 patients who underwent orthopedic surgery. INTERVENTION: A CDSS designed to provide immediate information pertaining to venous thromboembolism prevention among surgical patients was integrated into daily medical practice during three 10-week intervention periods, alternated with four 10-week control periods, with a 4-week washout between each period. MAIN OUTCOME MEASURE: Proportion of appropriate prescriptions ordered for anticoagulation, according to preestablished clinical guidelines, during intervention vs control periods. RESULTS: Physicians complied with guidelines in 82.8% (95% confidence interval [CI], 77.6%-87.1%) of cases during control periods and in 94.9% (95% CI, 92.5%-96.6%) of cases during intervention periods. During each intervention period, the appropriateness of prescription increased significantly (P<.001). Each time the CDSS was removed, physician practice reverted to that observed before initiation of the intervention. The relative risk of inappropriate practice decisions during control periods vs intervention periods was 3.8 (95% CI, 2.7-5.4). CONCLUSIONS: In our study, implementation of clinical guidelines for venous thromboembolism prophylaxis through a CDSS used routinely in an orthopedic surgery department and integrated into the hospital information system changed physician behavior and improved compliance with guidelines. JAMA. 2000;283:2816-2821

Anticoagulants↗
PubMed1991

The incidence and significance of thromboembolic complications in patients with high-grade gliomas.

Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high-grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patient's death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high-grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined.

Adult↗
PubMed1994

Therapy of venous thromboembolism in patients with brain metastases.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are common in patients with brain metastases. Few data exist to help guide the clinician's choice between the two therapeutic options of anticoagulation and inferior vena cava filter placement. METHODS: The authors reviewed their institutions' experience with the treatment of venous thromboembolism in 51 adult patients with known brain metastases since 1980. RESULTS: Ten patients were initially treated with Greenfield filters; four (40%) had recurrent nonfatal thromboembolic events (two PE and two DVT), and three required anticoagulation. Thirty-nine patients were treated initially with anticoagulation; none of these patients later received filters. Two patients with DVT were untreated and both died of PE. Among 42 patients who received anticoagulation, the duration of anticoagulation ranged from 5 to 563 days (mean, 100 days). Two patients who received anticoagulation experienced devastating central nervous system hemorrhage in the setting of supratherapeutic anticoagulation by conventional laboratory criteria. A third patient experienced a minor deterioration, possibly attributable to hemorrhage, for a 7% (3 of 42) incidence of serious central nervous system complications. Three asymptomatic patients developed hyperdensity within metastases on routine follow-up noncontrast computed tomography scan, suggesting possible intratumoral hemorrhage. Three patients taking warfarin had recurrent DVT with prothrombin time between 15.1 and 17.7. Systemic bleeding complications were generally minor and occurred in only eight patients (19%). CONCLUSIONS: Anticoagulation is more effective than Greenfield filters and acceptably safe when maintained in the therapeutic range in most patients with brain metastases and venous thromboembolism.

Adult↗
PubMed2003

Once versus twice daily LMWH for the initial treatment of venous thromboembolism.

BACKGROUND: In the initial treatment of venous thromboembolism (VTE) low molecular weight heparin (LMWH) is administered once or twice daily. A once daily treatment regimen is more convenient for the patient and may optimise home treatment. However it is not clear whether a once daily treatment regimen is as safe and effective as a twice daily treatment regimen. OBJECTIVES: The objective of this review was to compare the efficacy and safety of once daily administration to a twice daily administration of LMWH. SEARCH STRATEGY: Trials were identified through the Specialised Register of the Cochrane Peripheral Vascular Diseases Group (last searched May 2001), the Cochrane Controlled Trials Register (CCTR/CENTRAL) (last searched Issue 1, 2002), by hand-searching other relevant journals, by checking cross-references and through personal communication with experts. SELECTION CRITERIA: Randomised clinical trials in which a once daily treatment regimen with LMWH is compared to a twice daily regimen in the initial treatment of patients with venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trials on criteria for inclusion and extracted the data independently. MAIN RESULTS: Five studies were included with a total of 1508 patients. The pooled data showed a statistically non-significant difference in recurrent venous thromboembolism between the two treatment regimens (OR 0.82; 0.49 - 1.39). A comparison of major haemorrhagic events (OR 0.77; 0.40 - 1.45) and mortality (OR 1.14; 0.62 - 2.08) also showed a statistically non-significant difference between the two treatment regimens. REVIEWER'S CONCLUSIONS: Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH. However, the 95% confidence interval implies that there is a possibility that the risk of recurrent VTE might be higher when patients are treated once daily. Hence the decision to treat the patient with a once daily regimen will depend on the evaluated balance between increased convenience and the potential for a lower efficacy.

Anticoagulants↗
PubMed2005

Once versus twice daily LMWH for the initial treatment of venous thromboembolism.

BACKGROUND: In the initial treatment of venous thromboembolism (VTE) low molecular weight heparin (LMWH) is administered once or twice daily. A once daily treatment regimen is more convenient for the patient and may optimise home treatment. However, it is not clear whether a once daily treatment regimen is as safe and effective as a twice daily treatment regimen. OBJECTIVES: To compare the efficacy and safety of once daily versus twice daily administration of LMWH. SEARCH STRATEGY: We identified trials through searching the Specialised Register of the Cochrane Peripheral Vascular Diseases Group (last searched April 2005), the Cochrane Central Controlled Trials Register (CENTRAL) (last searched Issue 2, 2005), handsearches of relevant journals, checking cross-references and through personal communication with experts. SELECTION CRITERIA: Randomised clinical trials in which LMWH given once daily is compared to LMWH given twice daily for the initial treatment of venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two authors assessed trials for inclusion and extracted data independently. MAIN RESULTS: Five studies were included with a total of 1508 participants. The pooled data showed a statistically non-significant difference in recurrent venous thromboembolism between the two treatment regimens (OR 0.82, 0.49 to 1.39). A comparison of major haemorrhagic events (OR 0.77, 0.40 to 1.45) and mortality (OR 1.14, 0.62 to 2.08) also showed a statistically non-significant difference between the two treatment regimens. AUTHORS' CONCLUSIONS: Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH. However, the 95% confidence interval implies that there is a possibility that the risk of recurrent VTE might be higher when people are treated once daily. Hence, the decision to treat a person with a once daily regimen will depend on the evaluated balance between increased convenience and the potential for a lower efficacy.

Anticoagulants↗
PubMed2002

Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism.

Case-control studies have indicated increased risk of venous thrombosis associated with the prothrombin gene G20210A polymorphism and with elevated plasma prothrombin levels. We sought to confirm these results in a prospective population-based study of 21,690 persons. We measured G20210A and prothrombin antigen on pre-event blood samples of 302 participants who developed venous thromboembolism (VTE) and 626 participants who remained free of VTE. Approximately 4.0% of cases and 2.4% of controls carried the G20210A polymorphism, but only one of 137 African Americans did. The odds ratio in whites was 1.87 (95% CI = 0.85, 4.11)--higher for those who reported a prior history of VTE (OR = 5.44) than those reporting no VTE history (OR = 1.41) and in those with idiopathic VTE (OR = 2.51) than those with secondary VTE (OR = 1.38). There was no association between venous thromboembolism and plasma prothrombin antigen level. We estimated that the G20210A polymorphism may account for approximately 2.5% of venous thromboembolism events in United States whites.

Age Factors↗
PubMed1993

Hereditary thrombophilia among 217 consecutive patients with thromboembolic disease in Jordan.

This is a four-year prospective study on patients admitted or referred with thromboembolic disease to Jordan University Hospital or to the Thrombosis/Haemostasis Laboratory at the University of Jordan. The aim of the study was to find the relative prevalence of hereditary thrombophilia. For the purpose of this work, hereditary thrombophilia was diagnosed in the absence of an acquired cause of thrombophilia in addition to two of the following: 1) positive family history of thrombophilia, 2) confirmed same deficiency in a closely related family member, 3) the deficient protein is constantly below 2 SD of the normal mean on repeated testing. All ages were admitted to the study. Acquired systemic factors or local factors known to cause thrombosis or affect the levels of proteins opposing thrombosis were excluded. There were a total of 217 patients (102 males and 115 females) with confirmed thromboembolic disease. Their mean age was 34 years. A total of 49 patients (26 males and 23 females) fulfilled the criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3 dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. In this group most of the thrombosis was venous. A positive family history was obtained in 65.3% of patients with hereditary thrombophilia. Twenty-seven additional relatives with deficiency were identified upon family studies. The calculated prevalence of hereditary thrombophilia in Jordan is put at 1/25,000. Screening for PC, PS, and ATIII is advocated in young patients who have thromboembolic disease, especially when there is a positive family history of thrombosis.

Adolescent↗
PubMed1981

The effect of dihydroergotamine and heparin on the incidence of thromboembolic complications following total hip replacement: a randomized controlled clinical trial.

A randomized blind clinical trial was carried out to assess the effect of dihydroergotamine (DHE) alone and in combination with heparin on the incidence of thromboembolic complications of total hip replacement. It was found that a combination of DHE 0.5 mg and heparin 5000 units subcutaneously, given 8-hourly in separate injection sites, reduced the incidence of thromboembolic complications from 63 per cent in the untreated controls to 7.4 per cent in the treated group. This difference was highly significant. DHE alone produced a reduction in the incidence of thromboembolism but this reduction was not statistically significant. Blood loss was calculated using pre- and postoperative haemoglobin levels, taking into account the amount of blood transfused. It was found that the blood loss in the DHE/heparin-treated patients was identical to that in the untreated controls. The patients who received DHE alone had a significantly lower mean blood loss than the other two groups. It is concluded that this reduction in blood loss by DHE may be due to its venoconstrictor properties.

Aged↗
PubMed1989

Effect of blood gases and pH on thromboembolic reactions in rabbit mesenteric microvessels.

The influence of changes in systemic blood gas and pH values on the thromboembolic reaction following wall puncture was studied in rabbit mesenteric arterioles and venules (diameter 20-40 microns), using intravital video-microscopy. Under normal circumstances the number of emboli produced was higher in arterioles than in venules (6 and 1, respectively). The initial thrombus growth, the number of emboli produced per vessel and the total duration of the embolisation period were not significantly influenced by changes in blood gas and pH values in both arterioles and venules. Therefore, the observed difference in thromboembolic reaction between arterioles and venules cannot be explained by differences in blood gas and pH values in these microvessels. Since reduced velocity, as a measure of wall shear rate, did not correlate with the thromboembolic reaction in arterioles or venules, fluid dynamics can also not explain the difference, indicating that the thrombogenic or antithrombogenic activity of arteriolar and venular walls differs following injury. A combination of hypercapnia and hypoxia was found to result in a prolongation of the average time period needed to produce a new embolus in both vessel types. This prolongation in embolus production time was largely due to the occurrence of periods, in which the thrombus did not grow, reflecting hampering of the adhesion and aggregation of blood platelets to a growing thrombus under hypercapnic/hypoxic conditions.

Animals↗
PubMed1994

Prevention of postoperative venous thromboembolism following laparoscopic cholecystectomy.

Advantages of laparoscopic cholecystectomy are less patient discomfort and shorter hospital stay than with the traditional open approach. Nevertheless, this operation is performed under general anesthesia, using muscle relaxants and pneumoperitoneum, with most patients in the reverse Trendelenburg position. It has been shown that this procedure is associated with significant hypercoagulability and dilation of the veins of the leg. We review the role of these factors as potential risk factors for the development of postoperative venous thromboembolism and also report the rate of thromboembolic complications following laparoscopic cholecystectomy. Based on the available evidence, it is concluded that laparoscopic cholecystectomy, despite being a "minimally invasive procedure," may be associated with a definite risk of developing postoperative venous thromboembolism that could extend beyond hospital discharge. Accordingly, thrombosis prophylaxis should be considered for these patients.

Cholecystectomy, Laparoscopic↗
PubMed1994

Treatment of thromboembolic complications in patients with brain tumors.

Thromboembolic disease is common in patients with malignant brain tumors and represents a major cause of morbidity and mortality in these patients. The presenting signs and symptoms of deep venous thrombosis and pulmonary emboli can be subtle; thus, a high index of suspicion is required to ensure a timely diagnosis. The accuracy of non-invasive studies of the lower extremities and lungs have significant limitations. Venography and pulmonary angiography remain the best diagnostic techniques when difficult decisions arise regarding the need for anticoagulants in these patients. Patients with malignant brain tumors can be safely anticoagulated with heparin and warfarin, if these agents are monitored carefully. Continuous intravenous infusions of heparin are associated with lower risks of bleeding than intermittent boluses. Clinicians may wish to modify the recommended initial bolus dose of heparin in patients without life-threatening thromboembolic disease. Warfarin reduces the incidence of recurrent thromboembolic events. The incidence of warfarin-related bleeding can be lowered without compromising efficacy by maintaining the PT ratio at 1.3. Potential warfarin drug interactions must be considered, aspirin containing medications and NSAIDS should be avoided, and the platelet count should be kept above 50,000 using transfusions if required to prevent potentially life-threatening bleeding in anticoagulated patients. Thrombolytics are contraindicated in this patient population. Vena caval filters and thrombectomy are rarely required. Additional research is needed to determine the best techniques to prevent deep venous thrombosis and pulmonary embolism in patients with brain tumors.

Brain Neoplasms↗
PubMed2001

[Anticoagulation in primary prevention of thromboembolism in advanced left ventricular dysfunction].

BACKGROUND: Patients with heart failure have an increased risk for thromboembolic events. In clinical practice the physician is often confronted with the decision to establish a prophylactic anticoagulation. DATA: The incidence for clinical embolization is 1.5 to 3.5% per year. It seems that patients with a lower peak oxygen uptake and with a lower ejection fraction are at higher risk for embolic events. There is no evidence for a correlation of such events with the clinical classification (NYHA) or with the genesis of heart failure. Concerning a prophylactic anticoagulation, the results of the published studies and meta-analyses are inhomogenous with a benefit in some, no difference in others and a significant disadvantage for the patients with anticoagulation in a part of them compared to a non-treated control group. None of these data is established by a prospective, randomized, controlled study with the primary endpoint thromboembolic event in patients with or without anticoagulation. The incidence for a hemorrhage under anticoagulation is 0.6-5.3% per year for life-threatening and 0.04-0.64% for fatal bleeding. CONCLUSION: Because of similar incidences for thromboembolic events and for the bleeding complication of anticoagulation, there is no evidence for a general indication for anticoagulation of patients with heart failure, persistent sinus rhythm and lack of risk factors. In patients with high-grade heart failure (e.g. VO2max < 14 ml/min/kg body weight or left ventricular ejection fraction < 20-30%), who belong to a high-risk population, anticoagulation should be considered and may be acceptable in individual cases.

Anticoagulants↗