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PubMed2002

Prophylaxis of thromboembolism in spinal injuries--survey of practice in spinal units in the British Isles.

AIM: Survey and discussion of the current thromboembolic prophylaxis practice in spinal injury units within the British Isles. BACKGROUND: Deep vein thrombosis and pulmonary embolism are major causes of morbidity and mortality in patients with spinal injuries. A wide range of thromboprophylactic measures have been proposed. The optimum treatment and duration for thromboprophylaxis in spinal injuries is unknown. Different spinal units within the British Isles use different measures despite similar training backgrounds. The present study was performed to review practice and make suggestions on best practice using literature review. METHODS: All the 13 regional and national spinal injury referral centres within the British Isles were contacted to find out their protocols for thromboembolic prophylaxis in patients with acute spinal injuries. RESULTS: All units replied. A wide variation in methods used was found in different spinal units ranging from no chemical prophylaxis to oral anticoagulation with warfarin and contrasting views on the use of antithromboembolic stockings. CONCLUSION: All units recognised the risk of thromboembolism after spinal injuries. A wide variety of thromboprophylactic measures are used.

Anticoagulants↗
PubMed1987

Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults.

Eleven of 204 children with nephrotic syndrome had thrombotic complications: arterial thrombosis in five, venous thrombosis in four, and pulmonary embolism in two. Fifty-one episodes of thromboembolism were recognized in 116 adult patients with nephrotic syndrome. Despite the lower incidence, thromboembolic complications tended to be more severe in children. In vitro indices of hemostasis and clinical evidence of thromboembolic complications were compared in children and adults. Antithrombin III concentrations and activities were abnormal in seven of 10 children, but in only two of 32 adults. In both groups, alpha 2-macroglobulin was elevated, but more markedly so in children. No evidence for circulating granulocyte-derived proteases (elastase/antielastase complexes) was noted in either group. Protein C was significantly elevated in children with nephrotic syndrome, but was normal in adults. Children also differed from adults with nephrotic syndrome in laboratory evidence of subthreshold disseminated intravascular coagulation (i.e., elevated soluble fibrinogen monomeric complexes and fibrin degradation products) and indicators of in vivo platelet activation (elevated beta-thromboglobulin). The more severe coagulation abnormalities in children may be linked to the more pronounced hypoalbuminemia.

Adolescent↗
PubMed1995

Effects of dipyridamole in combination with anticoagulant therapy on survival and thromboembolic events in patients with prosthetic heart valves. A meta-analysis of the randomized trials.

The addition of dipyridamole, an antiplatelet agent, to conventional anticoagulant regimens has been shown to reduce the frequency of embolization after valve replacement with a mechanical prosthesis. The purpose of this meta-analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence from all randomized clinical trials. Summary data were extracted from the application to the Food and Drug Administration. Six randomized clinical trials had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and 559 received additional dipyridamole at dosages ranging from 225 to 400 mg per day. The events analyzed were all thromboembolic events, both fatal and nonfatal; hemorrhagic events, both fatal and nonfatal; and the overall mortality. The combination of dipyridamole with anticoagulants reduced the risk of thromboembolic events (fatal or nonfatal) by 56% when compared with the use of anticoagulants alone (p = 0.0001). The risk reduction was seen in fatal and in nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008; for nonfatal events, 50%, p = 0.005). The overall mortality rate was also significantly reduced by 40% in the group receiving dipyridamole (p = 0.013). There was no difference between treatment groups with respect to hemorrhagic events (risk reduction, -1%, p = 0.94). This meta-analysis supports the use of dipyridamole in this setting and warrants further trials with new antiplatelet agents.

Anticoagulants↗
PubMed1986

Thromboembolic splenic infarction.

Splenic infarction occurs as a consequence of systemic thromboembolization in association with several cardiovascular disorders. We describe a case of splenic infarction in a patient who had paroxysmal atrial fibrillation after aortic valve replacement. In an autopsy series of 96 consecutive cases of splenic infarction, only 10% had been suspected clinically even though the splenic infarctions had contributed substantially to morbidity and mortality in 44% of the cases. Thromboembolic causes were responsible for the splenic infarcts in 67% of the cases, and concomitant infarcts in other organ systems were found in 62%. Embolization of atheromatous debris from the aorta, thrombotic elements from the left ventricle (in dilated cardiomyopathy and acute myocardial infarction), and vegetations from infected valves are the most common settings in which thromboembolic splenic infarcts are noted. The clinical picture associated with splenic infarction is typically nonspecific; manifestations may include fever, tachycardia, and left-upper-quadrant tenderness. Computed tomographic scanning and, to a lesser degree, ultrasonography are the imaging techniques of choice for diagnosing splenic infarction.

Aortic Valve Stenosis↗
PubMed1997

Third-generation oral contraceptives and thromboembolism risk.

Recently, observational studies have suggested an increased risk of nonfatal venous thromboembolic complications in women using oral contraceptives (OCs) containing the third-generation progestins, gestodene and desogestrel. Because of the observational, rather than randomized, nature of these trials, the clinical relevance of these findings is difficult to interpret. Each study included one or more potential sources of bias. In particular, cases came almost exclusively from hospitalized patients with nonfatal venous thromboembolism, which represents only a minority of patients diagnosed with this condition according to current clinical practice. In the absence of a sound biologic rationale to explain the increased risk with third-generation OCs, and considering the potential sources of bias within the current studies, an alternative view argues against causality. Oral contraceptives remain safe and effective. Clearly, additional research is needed to determine the relationship between thromboembolic disease and the use of third-generation OCs. In the interim, women should be informed thoroughly with objective data on all risks associated with the use of OCs.

Contraceptives, Oral, Combined↗
PubMedDate not supplied

Stratification of thromboembolic risk of atrial fibrillation by transthoracic echocardiography and transesophageal echocardiography: the relative role of left atrial appendage function, mitral valve disease, and spontaneous echocardiographic contrast.

The role of transesophageal echocardiography (TEE) in thromboembolic risk stratification in atrial fibrillation (AF) has not been established. Left atrial appendage contractile dysfunction in patients with AF predisposes to thrombus formation. The extent of blood stasis and propensity for thrombus can be assessed during TEE by measurement of the peak Doppler velocity of blood outflow from the appendage. Spontaneous echocardiographic contrast (SEC) is a swirling pattern of blood echogenicity that may be detected by TEE in the left atrium in patients with AF. The presence of SEC reflects left atrial blood stasis and a prothrombotic state. SEC is associated with an increased risk of systemic thromboembolic events. Parameters derived from TEE may provide additional prognostic data to clinical history and transthoracic echocardiography in thromboembolic risk stratification in AF.

Atrial Fibrillation↗
PubMed2002

CT for thromboembolic disease.

CTPA has dramatically changed the diagnostic approach to PE in the last decade. The addition of CTV has created a single diagnostic test that can evaluate for both important components of venous thromboembolic disease. Newer, multislice scanners will provide thinner images and more complete anatomic coverage. Shorter scan times will minimize motion artifacts. These improvements may continue to improve the diagnostic yield of CTPA. The availability of an accurate noninvasive diagnostic tool to evaluate for PE and DVT should lead to a better understanding of the wide range of presentations of thromboembolic disease. The next decade may produce improvements in understanding of the epidemiology of PE and perhaps to a more tailored approach to treatment for thromboembolic disease.

Acute Disease↗
PubMed2000

For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same?

Low-molecular-weight heparin compounds have been used in the treatment of patients with venous thromboembolism for approximately 15 years. Ever since their introduction, there has been discussion about whether low-molecular-weight heparin compounds differ in their efficacy and safety. The best answer would be provided by direct comparison of different low-molecular-weight heparin preparations; however, these trials have not been conducted. Classical meta-analysis has its limitations for such a comparison since only a very small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been the use of meta-regression to compare the efficacy and safety of different low-molecular-weight heparin compounds in the initial treatment of patients with venous thromboembolism. We used computerized literature searches to identify studies that compared dose-adjusted unfractionated heparin treatment with fixed dose subcutaneous low-molecular-weight heparin treatment in patients with established venous thromboembolism. The individual odds ratios of the studies were plotted against the absolute percentage of the major outcomes in the unfractionated heparin control group. Linear regression was used to find differences between different low-molecular-weight heparin compounds. There appears to be some variation in efficacy and safety among the currently available low-molecular-weight heparin preparations.

Anticoagulants↗
PubMed2000

The pre-, peri-, and postsurgical activation of coagulation and the thromboembolic risk for different risk groups.

Patients after surgery stand at high risk of developing thromboembolic complications. Nevertheless, there is at present no universal and valid guideline on the duration of heparin prophylaxis. This study aims to assess the thromboembolic risk after the different surgical treatments for different risk groups, based on the activation of the plasmatic coagulation and fibrinolysis system. This is measured by estimating the levels of the fibrin monomers (FM) and fibrin-D-dimers (FD) in plasma during the pre-, peri-, and postsurgical periods in patients from the different clinical risk categories (i. e., posttraumatic or elective hip replacement and osteosynthesis and abdominal surgery: conventional or minimal invasive in malignant and non malignant diseases). During an observation period of 14 days the FM and FD levels were found to be significantly elevated in patients from all risk groups. Underlying malignant diseases lead to an elevation of the procoagulatory risk, whereas age itself does not. Patients who underwent hip surgery seemed to be especially at risk. Even after 14 days or at the date of discharge the FM and FD levels were elevated to maximum showing sustained precoagulatory conditions and increased thromboembolic risk. For these patients the long-term prophylaxis, lasting possibly longer than the average hospitalization period, seems evident. Clinical trials to prove this hypothesis are nevertheless urgently recommended. A corresponding clinical trial that compares long-term against standard heparinization was therefore initiated and is now in progress.

Adult↗
PubMed1997

Delayed adjuvant therapy with the 21-aminosteroid U74006F and the anion channel blocker L644-711 does not improve outcome following thrombolytic therapy in a rabbit model of thromboembolic stroke.

BACKGROUND: Both the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, and L644-711, an anion channel blocker that inhibits both neutrophil and astrocyte function, have been previously shown to reduce brain injury in pretreatment paradigms of cerebral ischemia. It was therefore of interest to examine the effect of these agents in combination, when given on a delayed basis as adjuvants to thrombolytic therapy in a rabbit model of thromboembolic stroke. METHODS: Animals were mechanically ventilated and arterial blood gases controlled. Core and brain temperature, intracranial pressure, and mean arterial pressure were continuously monitored. Regional cerebral blood flow and hematocrit were measured hourly. Blood samples were taken to measure neutrophil (aggregation and chemiluminescence) and platelet (aggregation) activity. Following delivery of an autologous clot via the carotid artery, all experiments were continued for an 8-hour period. U74006F (3 mg/kg I.V.) and L644,711 (12 mg/kg I.V.) or their vehicle control (n = 8, each group) were given 3.5 hours following autologous clot embolization. Both groups received tissue-type plasminogen activator (t-PA) (6.3 mg/kg I.V.), beginning 4 hours following thromboembolic stroke and continuing over a 2-hour infusion period. Infarct size was determined following staining and image analysis. RESULTS: In the L644,711/U74006F group, neutrophil chemiluminescence was reduced following drug therapy; however, there were no significant differences between groups regarding infarct size (50.3 +/- 8.7 vs. 49.9 +/- 10.6, treatment vs. t-PA control, mean +/- SEM), or in regional cerebral blood flow or intracranial pressure over time. CONCLUSIONS: It is concluded that prolonged (3.5 hours) delay of the initiation of therapy with the anion channel blocker L644,711 and the 21-aminosteroid U74006F fails to further reduce brain injury when given in combination with tissue plasminogen activator in a rabbit model of thromboembolic stroke.

Animals↗
PubMed1994

Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer.

Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.

Antineoplastic Agents↗
PubMed1999

Primary prevention of arterial thromboembolism in nonrheumatic atrial fibrillation: the PATAF trial study design.

Patients with nonrheumatic atrial fibrillation (NRAF) have a higher risk of thromboembolism than patients in sinus rhythm. Several trials have been conducted to establish the best preventive regimen in patients with NRAF, but not in the primary-care setting. The Primary Prevention of Arterial Thromboembolism in Nonrheumatic Atrial Fibrillation (PATAF) study, a primary-care-based trial, was set up to compare the preventive efficacy of low-intensity anticoagulation (AC), target range International Normalized Ratio (INR) 1.1 < INR < 1.6 and regular-intensity AC (2.5 < INR < 3.5) therapies with that of aspirin 150 mg/d for the occurrence of thromboembolism in NRAF patients. Patients eligible for regular-intensity AC were randomly assigned to aspirin at 150 mg/d, low-intensity AC, or regular AC in group I. In cases of noneligibility for regular AC, the trial randomized patients between aspirin and low-intensity AC (assigned to group II). Primary outcome events were stroke (including intracranial hemorrhage), systemic embolism, major hemorrhage, or vascular death. Analysis of the data was based on Cox regression to compute the hazard ratio (HR) with a 95% confidence interval, using the likelihood ratio test. The trial randomized 729 patients. Patient enrollment and follow-up has been stopped, and the final analysis is now complete. We shall publish the main results as soon as possible.

Aged↗
PubMed2000

[Prevention of thromboembolic disease in patients with heart disease].

OBJECTIVE: To evaluate the adequacy to thromboembolic disease prophylaxis protocol in patients with heart disease. DESIGN: Cross-sectional study. SUBJECTS: Patients older than 14 years affected of heart disease in a semi-urban health primary-care clinic with a population of 10,610 persons and 5582 clinical records. METHODS: Data about age, sex, cardiovascular risk factors, heart disease, prophylactic treatment and its adequacy to the protocol of the "thromboembolic disease commission" of the reference hospital were analysed. RESULTS: Age 67 +/- 13 years (mean +/- SD). Cardiovascular risk factors: hypertension 40%, diabetes 33%, dyslipemia 15%, smoking 21%. Heart disease: ischemic cardiopathy 48%, atrial fibrillation 15%, valvulopathy 19%, dilated myocardiopathy 4% and other 14%. In 20% of cases had two different affections (80% with atrial fibrillation). Prophylactic therapy: 52% of patients were under prophylactic treatment (35% antiaggregation, 18% anticoagulation). Among antiaggregants, drugs used were acetylsalicylic acid 73.5%, triflusal 14.7%, dipyridamole, 8.8% and ticlopidine 3%. In 53% of people without prophylactic treatment antiaggregation criteria were present. 15% of patient under antiaggregation therapy did not meet antiaggregation criteria, and 6% fulfilled anticoagulation criteria. 67% treatments accorded the reference protocol, without significant differences between kind of heart disease or sex. The only statistically significant difference was found in age: 46% of patients older than 80 year were correctly treated, in front 75% adequacy in younger people. CONCLUSION: Prophylactic antithrombotic therapy was according the reference protocol in 67% of cases. In older patients, with greater risk of thromboembolic disease, the adequacy is worse.

Age Factors↗
PubMed2004

[How suitable is thromboembolism prophylaxis for patients with chronic auricular fibrillation at 3 primary care centers].

OBJECTIVE: To find just how suitable thromboembolism prophylaxis (TEP) is in a group of patients with chronic auricular fibrillation belonging to the primary care environment. DESIGN: Cross-sectional and descriptive multi-centre study. SETTING: The study was performed at 3 urban primary care centres in Madrid. PARTICIPANTS: All the patients recorded up to April 2001 with the diagnosis of chronic auricular fibrillation (n=274) were included. Patients with no clinical history or who had a valve prosthesis were excluded. MAIN MEASUREMENTS: Demographic variables, existence of factors of risk of embolism, presence of counter-indications for oral anti-coagulants, and the kind of thromboembolic prophylaxis taken were collected. RESULTS: A total of 274 patients were evaluated. Average age was 75 (SD, 9) and 52% were women. 82% of patients had at least one factor of risk of thromboembolism. The most commonly used kind of TEP was oral anti-coagulants. 45% of patients did not receive suitable TEP. 13.5% of patients at risk of embolism and who had no kind of TEP were found. CONCLUSIONS: There is a high percentage of patients with chronic auricular fibrillation and a high risk of embolism, who do not receive adequate TEP, in the absence of counter-indications to taking oral anticoagulants. There is great scope for improvement, which is within professionals' possibilities.

Age Distribution↗
PubMed1999

[Improvement in prevention of venous thromboembolism in medical environment. Mission impossible?].

PURPOSE: In France, low molecular weight heparins are widely used for prophylaxis of venous thromboembolism. This practice is not based on strong evidence supporting the use of this technique, thus leading to important difficulties in defining accurate guidelines. Improvement in the prophylaxis must focus on the process leading to prescription or non-prescription. Our primary objective was to identify and describe this process. We also analyzed the causes for dysfunction and implemented corrective actions. METHODS: Basic tools and methods specific to improvement of quality were used including: flow charting for process description, causes-effect diagram for updating and analysis of dysfunction, weighted vote for decisions regarding corrective actions, and agenda and designation of leaders for the implementation of corrective actions. RESULTS: The theoretical process beginning with the recognition of a risk and ending with the adequate treatment or prevention of this risk was demonstrated. The most important dysfunction was the lack of epidemiological and clinical trials. Key corrective actions were the following: standardization of practices where evidence was available; if not, collaborative efforts to collect valid epidemiological data through multicenter surveys and clinical trials; systematic appraisal of the quality of published data; assessment of the risk for venous thromboembolism during hospitalization. To achieve real improvement in practice, priority was given to repeated measures of the risk for thromboembolism. The use of low molecular weight heparins has been so wide however, that it has led to some difficulties. We must draw lessons from this experience. CONCLUSION: Improvement of quality in terms of healthcare is not only based on auditing the practices or modifying the defective processes, but also on our ability not to use new drugs before fully assessing their validity.

Anticoagulants↗
PubMed2001

[Duration of oral anticoagulant therapy in venous thromboembolism].

PURPOSE: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. It is essential to balance the desired effect of the anticoagulants in reducing recurrences against the risk of major bleeding. The aims of this paper are to describe the current concepts in this field. CURRENT KNOWLEDGE AND KEY POINTS: Recent data, based on randomised controlled trials, suggest that it is necessary to tailor the duration of anticoagulation individually according to the topography of venous thromboembolism and the presence of risk factors. A 6-week treatment for patients with isolated calf vein thrombosis is sufficient. For proximal thrombosis and/or pulmonary embolism, a short anticoagulant course seems sufficient in patients with temporary risk factors (3 months) and a longer anticoagulant course (6 months at least) is recommended for cases with permanent risk factors or idiopathic venous thromboembolism. The inherited or acquired hypercoagulable states can be divided into those that are common and associated with a modest risk of recurrence (i.e., isolated factor V Leiden or G20210A prothrombin gene) and those that are uncommon but associated with a high risk of recurrence (i.e., antithrombin, protein C or S deficiencies and anticardiolipin antibodies). Thus, the presence of one of these last abnormalities favours more prolonged anticoagulant therapy. FUTURE PROSPECTS AND PROJECTS: 1) For patients at high risk of recurrence, there is a paucity of evidence-based medicine, particularly for patients with biological thrombophilia, and randomised controlled trials in this population are required. An assessment of low- or fixed-dose oral anticoagulation is also necessary in order to reduce the bleeding risk. 2) It is not always possible to precisely determine the optimal duration with the available data. We have performed a meta-analysis on summary data which suggests that a long course of oral anticoagulant therapy is superior to a short course. An individual meta-analytic approach is needed to draw more precise conclusions on an interesting and important clinical topic and we propose to perform this analysis in a international collaborative group.

Administration, Oral↗
PubMed2001

G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism.

OBJECTIVES: The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden. BACKGROUND: Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial. METHODS: A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years. RESULTS: A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9-12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0-14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up. CONCLUSIONS: In a prospective evaluation of 218 men, the presence ofprothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.

Adult↗
PubMed1986

Thromboembolism and antithrombotic therapy in peripheral arterial disease.

Atherosclerosis complicated by thromboembolism is the main cause of obstructive arterial disease in the legs. Two studies from West Germany suggest that antiplatelet drugs may slow the progress of atherosclerosis in leg arteries and prevent occlusive thrombosis under some circumstances. The same agents may also reduce the risk of rethrombosis after successful vascular repair in the femoropopliteal region; in one trial, aspirin decreased the incidence of reocclusion after thromboendarterectomy and, in another, the combination of aspirin and dipyridamole was effective after bypass with synthetic material. Antithrombotic drugs are used in most centers after percutaneous transluminal angioplasty, but there is no definite evidence for their need. Thus, it appears that in contrast to cardiac and cerebrovascular disease, few efforts have been made to determine the true value of antithrombotic therapy in peripheral arterial disease. The management of acute thromboembolism in the legs requires a multidisciplinary approach. Depending on the type (embolic or thrombotic), length and localization of the arterial occlusion, surgical (embolectomy, thromboendarterectomy, peripheral bypass surgery) or nonsurgical (systemic fibrinolysis or local thrombolytic therapy with or without balloon angioplasty) treatment is preferred. The importance of nonsurgical therapeutic approaches may become even greater in elderly patients with a poor operative risk. This review discusses the available therapeutic modalities in acute and chronic peripheral thromboembolic arterial disease.

Angioplasty, Balloon↗