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Cost-effectiveness of prophylactic low molecular weight heparin in pregnant women with a prior history of venous thromboembolism.

PURPOSE: Women with a history of prior venous thromboembolism have an increased risk for recurrence during pregnancy. Although thromboprophylaxis reduces this risk, recent evidence suggests that, in many cases, prophylaxis can be safely withheld because the estimated recurrence risk is very low. The balance of risks and benefits in women with different recurrence risks has not been examined. METHODS: We developed a Markov state transition decision analytic model to compare prophylactic low molecular weight heparin to expectant management for pregnant women with a single prior venous thromboembolism. A lifetime time horizon and societal perspective were assumed. Input data were obtained by literature review. Outcomes were expressed as U.S. dollars per quality-adjusted life-year (QALY). RESULTS: For "low-risk" women with a prior venous thromboembolism associated with a transient risk factor and no known thrombophilic condition (recurrence risk 0.5%), expectant management was both more effective and less costly than prophylaxis. For "high-risk" women with prior idiopathic venous thromboembolism or known thrombophilic condition (recurrence risk 5.9%), prophylaxis was associated with a reasonable cost-effectiveness ratio (USD 38,700 per QALY) given a risk of bleeding complications <1.0% (base case 0.5%). CONCLUSION: For low-risk women with prior venous thromboembolism, expectant management during pregnancy leads to better outcomes than administration of prophylactic low molecular weight heparin. For high-risk women, antepartum thromboprophylaxis is a cost-effective use of resources.

Anticoagulants↗

[Prophylaxis of thromboembolic complications in obstetrics and gynaecology].

Venous thromboembolism is a leading cause of maternal mortality in many countries, including France. Most enquiries have repeatedly demonstrated that many deaths could be avoided, suggesting the need to update and ensure a wider diffusion of recommendations. Although thromboembolism-induced maternal death plays a major role, the absolute incidence of events remains low, reducing the ability to perform well-designed research and the level of recommendations presented. Many personal or pregnancy-related factors have been identified as increasing the risk of thromboembolism in pregnant patients but few of them have been associated with a significantly increased risk. A history of thromboembolic event and some thrombophilic factors (including antithrombin deficiency and antiphospholipid syndrome) carry the greatest risk. Pregnancy itself, caesarean delivery and the postpartum period, although associated with an increased risk play a minor role when not combined with other risk factors. Prophylactic treatment relies mainly on low molecular weight heparins which safety is now well established in pregnant patients. Dose and duration of treatment should be adapted to the perceived level of risk. The occurrence of a thromboembolic event is also increased after gynaecological surgery but major and cancer surgery carry the greatest risk. Here also, low molecular weight heparins play a leading role, although non pharmacologic means are useful. Dose and duration should be dependent on the level of risk.

Adult↗

Venous thromboembolism among United States soldiers deployed to Southwest Asia.

INTRODUCTION: Military operations may represent a high-risk environment for venous thromboembolism (VTE). We sought to identify and describe cases of venous thromboembolism among US military personnel serving in Southwest Asia, and estimate relative disease rates compared to non-deployed personnel. MATERIALS AND METHODS: Retrospective review of imaging archives, hospital discharge codes, case logs and autopsy records for the diagnosis of deep vein thrombosis or pulmonary embolism occurring from 1 March 2003 through 29 February 2004 among U.S. military personnel deployed to Southwest Asia. Rates of disease in deployed and non-deployed active-duty soldiers were estimated using personnel data and deployment experience obtained from automated rosters. RESULTS: Forty cases of venous thromboembolism were identified. The case-fatality rate was 16% (3/19) among those with pulmonary embolism. Antecedent trauma followed by prolonged air evacuation was present in 55% (22/40). Compared to trauma-associated cases, non-trauma cases were more commonly over 40 years old (44% vs. 5%; p<0.05), assigned to a transportation or quartermaster company (56% vs. 14%; p<0.05), or had a history of remote venous thromboembolism (31% vs. 0%; p<0.05). The overall incidence among deployed active-duty soldiers was 22.1/100,000 person-years. Compared to non-deployed active-duty soldiers, the age-adjusted incidence rate ratio was 1.06 (CI(0.95) 0.68-1.67). CONCLUSIONS: VTE rates among deployed soldiers are relatively low compared to the general population, and are comparable to non-deployed soldiers. Fatalities from PE are not uncommon, and vigilance among clinicians remains warranted. Trauma followed by prolonged air evacuation or ground transport during military operations may represent unique interactive risk factors for venous thromboembolism.

Adult↗

Arterial thromboembolic complications in patients with Starr-Edwards aortic ball valve prostheses.

Aterial thromboembolic complications were studied in 253 patients who had a single aortic Starr-Edwards ball valve implanted. During the first postoperative month, six patients died from myocardial infarction, one was reoperated because of leakage caused by thrombus on the valve, and five others suffered six thromboembolic episodes. Forty-six late thromboembolic complications occurred in 40 of the 216 patients who survived the postoperative period. Seven died, four from cerebral emboli and three from myocardial infarction. The late incidence was 7 episodes per 100 patients per year. Valves of series 1200 carried a significantly higher risk of arterial thromboembolism than did those of series 2300, and most episodes occurred in patients with cell controlled anticoagulant treatment. The incidence was not influenced by time since operation, continuous arrhythmia, concomitant mitral valve disease, heart size, or the degree of intravascular hemolysis. It is concluded that arterial thromboembolic complications represent a major threat to patients with aortic ball valves even several years after operation and in spite of intense anticoagulant therapy.

Aortic Valve↗

Risk of thromboembolic events in patients with atrial flutter.

Based on multiple studies, clear, guided anticoagulation therapy is recommended for patients with atrial fibrillation. The value of anticoagulation therapy in patients with atrial flutter, however, is less well established. Little is known about the incidence of thromboembolism in patients with atrial flutter. We evaluated the risk of thromboembolism in 191 consecutive unselected patients referred for treatment of atrial flutter. A history of embolic events was noted in 11 patients. Acute embolism (<48 hours) occurred in 4 patients (3 after direct current cardioversion, 1 after catheter ablation). During follow-up of 26+/-18 months, 9 patients experienced thromboembolic events. During the follow-up, the overall embolic event rate (including acute embolism and thromboembolic events during follow-up) was 7 % in this patient population. Risk indicators for an embolic event in an univariate analysis were organic heart disease (p = 0.037), depressed left ventricular function (p = 0.02), history of systemic hypertension (p = 0.004), and diabetes mellitus (p = 0.0038). Using multivariate analysis, a history of hypertension was the only independent predictor for elevated embolic risk in this patient population (odds ratio = 6.5; 95% confidence intervals 1.5 to 45). Thus, the thromboembolic risk is higher than previously recognized for patients with atrial flutter. Anticoagulation therapy may decrease this risk.

Aged↗

Thromboembolism in patients with aortic porcine bioprostheses.

Thromboembolism was prospectively studied in 215 patients who survived aortic valve replacement with porcine bioprostheses. All patients were anticoagulated with warfarin sodium during the first 3 postoperative months. Thereafter, 80 patients received aspirin (325 or 650 mg per day) and 135 received no antiplatelet or anticoagulant drugs. The two groups of patients were similar. Thromboembolic complications were carefully searched for during the follow-up interviews. Patients were removed from the study after a thromboembolic event unless there was no change in their management. The follow-up ranged from 6 to 80 months (mean, 36 months). The linearized thromboembolic rate in patients on a regimen of aspirin was 1.3% per patient-year and in patients not taking aspirin, 5.2% per patient-year (p less than 0.02). Replacement of the ascending aorta and patch enlargement of the aortic annulus with a Teflon graft were identified as significant risk factors for thromboembolism in patients with aortic porcine bioprostheses. These findings indicate that patients with aortic porcine bioprostheses should receive aspirin, especially if they also had replacement of the ascending aorta or patch enlargement of the aortic annulus with a Teflon graft.

Adolescent↗

Preference and compliance in postoperative thromboembolism prophylaxis among gynecologic oncology patients.

OBJECTIVE: To compare low molecular weight heparin and external pneumatic compression in terms of patient preference and compliance to determine if either of these two methods is superior in postoperative thromboembolism prophylaxis of gynecologic oncology patients. METHODS: A total of 211 patients undergoing major surgery for a suspected gynecologic malignancy were randomized to receive thromboembolism prophylaxis with either external pneumatic compression or low molecular weight heparin. Surveys regarding thromboembolism prophylaxis were completed by patients before surgery and approximately 7 days postoperatively. Patient preferences as well as reasons for patient dissatisfaction with prophylactic methods were elicited in the questionnaires. In addition, patient compliance with prophylaxis was recorded twice a day during hospitalization. Patients were not considered to be compliant with prophylaxis if the external pneumatic compression device was not functioning properly or if the administration of low molecular weight heparin was not given in a timely manner. RESULTS: The majority of patients were satisfied with the prophylactic method that they received to the extent that they would prefer the treatment they received to one they had not necessarily experienced. The postoperative preferences of 78% of patients receiving low molecular weight heparin and 74% of those wearing external pneumatic compression corresponded to what the patients actually received as a method of thromboembolism prevention. Patient compliance with prophylaxis was noted to be inadequate in ten of 104 (9.6%) patients receiving external pneumatic compression and seven of 103 (6.8%) patients receiving low molecular weight heparin. CONCLUSION: Pneumatic compression and low molecular weight heparin are similar both in terms of patient preference and compliance among gynecologic oncology patients receiving postoperative thromboembolism prophylaxis.

Adult↗

Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy.

OBJECTIVE: To estimate the incidence, timing, and associated clinical characteristics of objectively diagnosed pregnancy-associated venous thromboembolism. METHODS: We retrospectively reviewed venous thromboembolism cases (deep venous thrombosis and pulmonary embolism) that occurred between 1978 and 1996. Study inclusion criteria required the objective diagnosis with either Doppler ultrasound, venography, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or computed tomography or magnetic resonance imaging. RESULTS: Among 268,525 deliveries there were 165 (0.06%) episodes of venous thromboembolism (one per 1627 births). There were 127 cases of deep venous thrombosis and 38 cases of pulmonary embolism. Only 14% (23 of 165 patients) had a history of venous thromboembolism. Most cases of deep venous thrombosis were in the left leg (104 of 127, 81.9%), with nearly three quarters of them (94 of 127, 74.8%) occurring during the antepartum period. Among cases of antepartum deep venous thrombosis, half were detected before 15 weeks' gestation (47 of 95, 49.5%), and only 28 cases occurred after 20 weeks (P < .001). Most of the pulmonary embolisms occurred in the postpartum period (23 of 38, 60.5%) and were strongly associated with cesarean delivery (19 of 36,470 compared with four of 232,032, P < .001). CONCLUSION: The incidence of venous thromboembolism during pregnancy is lower than has been previously described. Most cases occurred in the antepartum period, with the risk of deep venous thrombosis appearing to begin even before the second trimester.

Adolescent↗

Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study.

BACKGROUND: The frequency and role of risk factors for venous thromboembolism related to air travel is uncertain. We aimed to establish the frequency of this disorder in a group of long distance air travellers and to investigate the role of potential risk factors. METHODS: We designed a prospective study into which we recruited individuals aged between 18 and 70 years, travelling for 4 h or more by aircraft. D-dimer measurement was done before and after travel. Participants with a negative D-dimer (<500 ng/L) before travel were included in the study. Those who became D-dimer positive or developed high clinical probability symptoms during the 3 months after travel were investigated with bilateral compression ultrasonography and CT pulmonary angiography. Suspected clinical and thrombophilic risk factors, and use of prophylactic measures, were assessed. FINDINGS: 1000 individuals were recruited, with 878 meeting inclusion criteria and completing the study. All participants travelled at least 10 h, with a mean total duration of air travel of 39 h (SD 12.5). 112 patients underwent radiological assessment on return. Frequency of venous thromboembolism associated with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of pulmonary embolism and five of deep venous thrombosis. Six patients with venous thromboembolism had pre-existing clinical risk factors, two had a recognised thrombophilic risk factor, two travelled exclusively in business class, five used aspirin, and four wore compression stockings. INTERPRETATION: Our results suggest an association between multiple long distance air flights and venous thromboembolism, even in individuals at low to moderate risk. The role of traditional risk factors and prophylactic measures in air travel-related venous thromboembolism needs further investigation.

Adolescent↗

[Venous thromboembolism and cancer].

INTRODUCTION: Thromboembolic venous disease, which includes both peripheral venous thrombosis and pulmonary embolism, is a frequent disorder in patients with cancer. Although thromboembolic manifestations may precede the diagnosis of cancer, the value of extensive clinical search for potential underlying cancer when faced with venous thromboembolic manifestations has not been demonstrated. CURRENT KNOWLEDGE AND KEY POINTS: Clinical and biological studies have demonstrated that acquired abnormalities in blood hemostasis, especially procoagulant factors, account for the onset of thromboembolic manifestations in patients with cancer. Classical anticoagulant therapy is associated with low efficacy and tolerance in patience with cancer who are at high risk for hemorrhagic complications and recurrence of thromboembolic disease. FUTURE PROSPECTS AND PROJECTS: Recent data suggest the value of anticoagulant therapy using either low molecular weight heparin or warfarin at low doses (INR < 2) according to the specific surgical or medical context.

Anticoagulants↗

[Diagnosis and treatment of thromboembolic events in pediatrics].

Thromboembolic events are an increasingly commonly recognized secondary complications in children treated for serious, life-threatening primary diseases. Nevertheless the incidence of venous thromboembolic disease remains 100 times less frequent in hospitalized children than hospitalized adults, as recent data suggest an incidence of 5,3/10.000 pediatric patients compared to an incidence of 2,5-5/100 in adult patients. Diseases usually associated with thromboembolic events in children are neoplasia, autoimmune or cardiac malformative disease. Contrarily to what is observed in the adult, the majority of deep vein thrombosis events occur at the upper limbs veins, usually at the place where devices for venous access like port-a-cath or central venous lines are inserted. Because of the relatively low incidence of venous thromboembolic events in children, the diagnostic approach used are largely extrapolated from guidelines obtained from adult studies. However, the diagnostic performances of some diagnostic tools like Doppler-Ultrasound are probably diminished in children. Moreover, the concept of developmental hemostasis, which stresses the point that the hemostatic system in children is quite different from the adult one, is widely accepted and clearly suggests that the diagnostic and therapeutic approach in pediatric patients may not be simply extrapolated from data obtained in adult studies. From a more practical point of view, the fact that the hemostatic system in children is a dynamic and evolving system, renders the therapeutic approach quite complex. In particular, doses of anticoagulants vary markedly across the pediatric age. The absence of adapted formulations of commonly used anticoagulants, for example the absence of liquid formulations of anti-vitamin K drugs, further complicates the administration and the correct monitoring of anticoagulation in children, and may diminish observance in adolescent patients. Even though the concept that "children are not little adults" is nowadays widely accepted, there is an urgent need for prospective studies to better assess the modalities of diagnosis and treatment of venous thromboembolic disease in this particular population.

Adult↗

Effect of high dose platelet inhibitor treatment on thromboembolism in Novacor patients.

BACKGROUND: Thromboembolism and bleeding are among the most hazardous complications following implantation of long-term left ventricular support systems. This report focuses on the effect of high dose platelet inhibitor treatment in patients with the Novacor system to prevent thromboembolic events. METHODS: Thirty-eight (out of 58) Novacor patients (43+/-11 years old) were studied in a non-randomized manner. Postimplantation: 20 patients were treated with heparin only (control group), whereas in the other 18 patients aspirin (3x330 mg/day) and dipyridamol (3x75 mg/day) were added to the treatment protocol (aspirin group). RESULTS: Age, body size, underlying heart disease and support interval were comparable among both groups, however, patients in the aspirin group were much sicker with regard to urgency status, postoperative right heart failure and hematologic disorders. Cerebral thromboembolic complications were lower in the aspirin group (33% of patients, 0.4+/-0.7 events) as compared to the control group (55% (P=0.18), 1.4+/-2.3 events (P=0. 048)). Non-cerebral thromboembolism of surgical relevance was rare. The incidence of bleeding complications was mildly increased in the aspirin group. CONCLUSION: The addition of high dose platelet inhibitors seems to lower the incidence of thromboembolism in Novacor patients.

Adult↗

Thromboembolism in heart failure: who should be treated?

The risk of thromboembolic complications in patients with heart failure and/or chronic left-ventricular systolic dysfunction is increased. Nevertheless, anticoagulant therapy in these patients is still a subject of debate. Atrial fibrillation is the only prospectively evaluated, proven thromboembolic risk factor and patients with atrial fibrillation benefit from long term anticoagulant therapy. The significance of other proposed thromboembolic risk factors in heart failure and/or chronic left-ventricular dysfunction such as gender, cause of myocardial disease, severity of heart failure, left-ventricular ejection fraction, left-ventricular thrombus, left ventricular aneurysm and history of previous thromboembolic event is less clear. This article summarizes key studies, assesses the incidence of thromboembolism, evaluates risk factors and proposes guidelines for anticoagulation of patients with heart failure and/or left ventricular systolic dysfunction.

Adult↗

Cancer and venous thromboembolism.

Venous thromboembolism occurs commonly in patients with cancer. The pathogenetic mechanisms of thrombosis involve a complex interaction between tumour cells, the haemostatic system, and characteristics of the patient. Among risk factors for thromboembolism are long-term immobilisation, especially in hospital, surgery, and chemotherapy with or without adjuvant hormone therapy. Although prophylaxis and treatment of thromboembolism in patients with cancer draw on the agents that are commonly used in those without cancer, there are many special features of patients with cancer that make use of these drugs more challenging. Low-molecular-weight heparins are the cornerstone of prophylaxis and treatment of venous thromboembolism in patients with cancer. These drugs have the potential to increase survival, at least in patients with more favourable outlook. About 10% of patients with idiopathic venous thromboembolism have an underlying malignant disorder that can be detected by extensive diagnostic investigation. However, the issue of whether screening for occult malignant disease ultimately improves prognosis and survival remains to be resolved.

Anticoagulants↗

Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden.

INTRODUCTION: To evaluate the pregnancy-associated risk of venous thromboembolism and the risk of stillbirth and miscarriage a multicenter, retrospective and controlled study was conducted in women carrying the homozygous factor V Leiden mutation and in an agematched control group of women from the normal population. PATIENTS AND METHODS: In 64 homozygous (median age 44 years, range 21-75 years) and in 52 control women from five different centers data on venous thromboembolism and pregnancy outcome were obtained. RESULTS: The 64 homozygous women had in total 212 pregnancies, the 52 control women had 118 pregnancies. In homozygous women 65% of pregnancies ended with delivery of a viable infant, 15% with fetal loss (3.3% stillbirth, 12% miscarriage) and 20% by pregnancy termination. In the control women 75% of pregnancies ended with delivery of a viable infant, 12% with fetal loss (1.7% stillbirth, 10% miscarriage) and 13% by pregnancy termination. The differences were statistically not significant. Venous thromboembolism occurred significantly more often in the homozygous women, in 4.2% (9/212) during pregnancy and in 4.7% (10/212) after delivery or pregnancy termination. None of the control women had a thromboembolic episode. CONCLUSION: Our data indicate that women with homozygous factor V Leiden have a high probability for a favorable pregnancy outcome. The increased risk for venous thromboembolism during pregnancy and after delivery would favor heparin prophylaxis during and after pregnancy in women homozygous for factor V Leiden.

Adult↗

Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriers.

A mutation in factor XIII (Val34Leu) was reported to protect against venous thromboembolism. We evaluated the effect of Val34Leu on thrombotic risk in 352 factor V Leiden carriers who were first-degree relatives of 132 thrombotic propositi carrying factor V Leiden. The total observation period was 2,594 years in 92 Val34Leu carriers and 7,444 years in 260 non-carriers. The annual incidence of a first episode of venous thromboembolism was 0.31% in Val34Leu carriers and 0.44% in non-carriers [relative risk (RR) for venous thromboembolism: 0.7, 95% CI 0.3-1.5]. Age-specific RR for venous thromboembolism were (for Val34Leu carriers and non-carriers respectively): 1.0 (95% CI 0.3-3.2) in the age group of 15-30 years, 0.4 (95%, CI 0.05-3.0) in the age group of 30-45 years, 0.6 (95% CI 0.1-2.9) in the group aged 45-60 years and 0.5 (95% CI 0.06-4.5) in relatives older than 60 years. In conclusion, the impact of FXIII Val34Leu on the venous thromboembolic risk is modest, suggesting that screening for this mutation in factor V Leiden carriers is not justified.

Adolescent↗

The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both.

Factor V Leiden and the G20210A mutation in the prothrombin gene are the most frequent abnormalities associated with venous thromboembolism. It is unknown whether the risks due to the presence of either mutation are of the same magnitude. We compared the prevalence and incidence rate of venous thromboembolism in relatives with either mutation or both. The finding of different rates might influence the strategies for primary prevention of thrombosis in carriers of these mutations. The study population included 1076 relatives of probands with the prothrombin gene mutation, factor V Leiden or both who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were non-carriers. The prevalence of venous thromboembolism was 5.7% in relatives with the prothrombin gene mutation, 7.8% in those with factor V Leiden, 17.1% in those with both mutations and 2.5% in non-carriers. Annual incidences of thrombosis were 0.13% [95% confidence interval (CI) 0.06-0.24], 0.19% (0.13-0.25), 0.42% (0.15-0.83) and 0.066% (0.03-0.11), respectively, and the relative risk of thrombosis was two times higher in carriers of the prothrombin gene mutation, three times higher in those with factor V Leiden and six times higher in double carriers than in non-carriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation is slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it is two or three times higher. These findings suggest that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations.

Adolescent↗

Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study.

Anticardiolipin antibodies, one of the family of 'antiphospholipid' antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.

Aged↗