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PubMed1996

Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

OBJECTIVE: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism. DESIGN: Matched case-control study. SETTING: 10 centres in Germany and United Kingdom. SUBJECTS: Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. RESULTS: Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year. CONCLUSIONS: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Adolescent↗
PubMed1997

Hormone replacement therapy and risk of venous thromboembolism: population based case-control study.

OBJECTIVE: To evaluate the association between use of hormone replacement therapy and the risk of idiopathic venous thromboembolism. DESIGN: Population based case-control study. SETTING: Population enrolled in the General Practice Research Database, United Kingdom. SUBJECTS: A cohort of 347,253 women aged 50 to 79 without major risk factors for venous thromboembolism was identified. Cases were 292 women admitted to hospital for a first episode of pulmonary embolism or deep venous thrombosis; 10,000 controls were randomly selected from the source cohort. MAIN OUTCOME MEASURES: Adjusted relative risks estimated from unconditional logistic regression. RESULTS: The adjusted odds ratio of venous thromboembolism for current use of hormone replacement therapy compared with non-users was 2.1 (95% confidence interval 1.4 to 3.2). This increased risk was restricted to first year users, with odds ratios of 4.6 (2.5 to 8.4) during the first six months and 3.0 (1.4 to 6.5) 6-12 months after starting treatment. No major risk differences were observed between users of low and high doses of oestrogens, unopposed and opposed treatment, and oral and transdermal preparations. The risk of idiopathic venous thromboembolism among non-users of replacement therapy was estimated to be 1.3 per 10,000 women per year. Among current users, idiopathic venous thromboembolism occurs at two to three times the rate in non-users, resulting in one to two additional cases per 10,000 women per year. CONCLUSIONS: Current use of hormone replacement therapy was associated with a higher risk of venous thromboembolism, although the risk seemed to be restricted to the first year of use.

Aged↗
PubMed2000

Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis.

OBJECTIVE: To compare the risk of idiopathic venous thromboembolism among women taking third generation oral contraceptives (with gestodene or desogestrel) with that among women taking oral contraceptives with levonorgestrel. DESIGN: Cohort and case-control analyses derived from the General Practice Research Database. SETTING: UK general practices, January 1993 to December 1999. PARTICIPANTS: Women aged 15-39 taking third generation oral contraceptives or oral contraceptives with levonorgestrel. MAIN OUTCOME MEASURES: Relative incidence (cohort study) and odds ratios (case-control study) as measures of the relative risk of venous thromboembolism. RESULTS: The adjusted estimates of relative risk for venous thromboembolism associated with third generation oral contraceptives compared with oral contraceptives with levonorgestrel was 1.9 (95% confidence interval 1.3 to 2.8) in the cohort analysis and 2.3 (1.3 to 3.9) in the case-control study. The estimates for the two types of oral contraceptives were similar before and after the warning issued by the Committee on Safety of Medicines in October 1995. A shift away from the use of third generation oral contraceptives after the scare was more pronounced among younger women (who have a lower risk of venous thromboembolism) than among older women. Fewer cases of venous thromboembolism occurred in 1996 and later than would have been expected if the use of oral contraceptives had remained unchanged. CONCLUSIONS: These findings are consistent with previously reported studies, which found that compared with oral contraceptives with levonorgestrel, third generation oral contraceptives are associated with around twice the risk of venous thromboembolism.

Adolescent↗
PubMed2004

Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy.

PURPOSE: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death. EXPERIMENTAL DESIGN: Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter. RESULTS: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy. CONCLUSIONS: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.

Administration, Oral↗
PubMed2006

Racial and gender differences in the incidence of recurrent venous thromboembolism.

Men have been reported to have a higher incidence of recurrent venous thromboembolism than women. However, it is not known if this gender effect holds among different racial/ethnic groups and for both venous thrombosis and pulmonary embolism. We conducted a retrospective analysis of 18- to 65-year-old Caucasian, African-American and Hispanic cases hospitalized in California with unprovoked venous thromboembolism. The principal outcome was recurrent venous thromboembolism 7-60 months after the index event. Among 11,514 cases that were followed for a mean of 3.0 years, men had a significantly higher rate (events/100 patient-years) of recurrent venous thromboembolism than women for both venous thrombosis [rate ratio (RR) = 1.5, 95% confidence interval (CI):1.3-1.8] and pulmonary embolism [RR = 1.3, 95%CI:1.0-1.6]. Among men the recurrence rate did not vary significantly between the racial/ethnic groups (p > 0.05). However, the recurrence rate among Hispanic women with venous thrombosis was significantly higher than in Caucasian women (p < 0.001) and was comparable to the rate in men. Both Hispanic and African-American women with pulmonary embolism had a higher recurrence rate compared with Caucasian women (p < 0.02) that was comparable to the rate in men. We conclude that women in California had a 40% lower risk of recurrent venous thromboembolism compared to men. Rates were comparable among men of different races, but there were significant inter-racial differences among women, which also varied with the type of initial event. The effect of gender on the risk of recurrent venous thromboembolism can not be generalized because it varies between racial/ethnic groups and with the type of index event.

Adolescent↗
PubMed1999

Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood.

BACKGROUND: Serum levels of lipoprotein(a) [Lp(a)] are determined largely by genetic variation in the gene encoding for apolipoprotein(a) [apo(a)], the specific protein component of Lp(a) that is very homologous to plasminogen. High plasma levels of Lp(a) increase the risk for premature atherosclerotic vessel diseases. We investigated the little-characterized role of Lp(a) as a risk factor for venous thromboembolic diseases, alone and in conjunction with established thrombophilic risk factors of proteins regulating blood coagulation and fibrinolysis. METHODS AND RESULTS: Serum levels of Lp(a) and lipids, protein C, protein S, and antithrombin, as well as the size of apo(a) isoforms and the presence of the factor V:Q(506) mutation, were determined in 186 consecutively admitted children from neonates to 18 years old with a history of venous thrombosis and in 186 age- and disease-matched control subjects. Children with a history of venous thrombosis had a significantly higher median Lp(a) level (19 versus 4.4 mg/dL) than control subjects. The risk for thromboembolic events in children with Lp(a) levels in the upper quartile, ie, >30 mg/dL, was 7.2 (95% CI, 3.7 to 14.5). The size of apo(a) isoforms was inversely related to Lp(a) levels and to the risk for thromboembolic events. Compared with the highest quartile of the apo(a) size distribution, the lowest quartile was associated with a risk of 8.2. In addition, multivariate statistical analysis gives evidence that the factor V:Q(506) mutation (OR/CI, 2.8/1.6 to 4.9), protein C (OR/CI, 6.5/2.1 to 19), and antithrombin deficiency (OR/CI, 10.4/1.2 to 90) were independent risk factors of childhood venous thrombosis. Coincidence of elevated Lp(a) with factor V:Q(506) mutation or deficiencies of protein C or antithrombin further increased the risk for thromboembolic events to 8.4. CONCLUSIONS: Lp(a) >30 mg/dL is a risk factor for venous thromboembolism in childhood. Lp(a) measurements should be included in the screening of causal factors in children with venous thromboembolic events.

Activated Protein C Resistance↗
PubMed1995

Thromboembolic complications after Fontan operations.

BACKGROUND: Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed. METHODS AND RESULTS: We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1 +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery. CONCLUSIONS: Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.

Adolescent↗
PubMedDate not supplied

Cumulative incidence of venous thromboembolism during pregnancy and puerperium: a hospital-based study.

Pregnancy is associated with an increased risk of venous thromboembolism. The rate of occurrence of this complication has not been reported from this area previously. The aim of this study was to establish the incidence of venous thromboembolism in pregnancy and puerperium by using objective diagnostic methods. From January 1986 to December 1998, 39,757 deliveries were registered at King Fahad Hospital, Al Baha, and 59 of these were referred to hematology services with a clinical suspicion of venous thromboembolism. The majority (86%) of these underwent objective diagnostic methods such as ascending venogram (AV) and color Doppler imaging (CDI) of the venous system for the diagnosis of deep venous thrombosis (DVT). Pulmonary scintigraphy was performed when available and echocardiography was included towards the end of the study. Fifty-nine patients with suspicion of pregnancy-associated venous thromboembolism (PAVTE) were studied. The diagnosis was confirmed in 50 patients, who received anticoagulation therapy. DVT was diagnosed in 35 (70%) cases and pulmonary embolism in 27 (54%) cases. The cumulative incidence of PAVTE was 1.25 cases per 1,000 deliveries (95% confidence interval = 0.89-1.16). One patient died during the study period (0.025 case per 1,000 deliveries). There was a predominance of venous thromboembolism during the postpartum period (66%), and DVT occurred more frequently in the left leg (77%). The risk of pregnancy-associated venous thromboembolism is low and a resulting death rare. Proximal or whole-limb DVT occurs more frequently and there is a predilection for the left leg. The majority of events occur in the postpartum period. A hypercoagulable state probably exists and needs further evaluation.

Adult↗
PubMed1994

Conformance of clinical practice to established recommendations for the diagnosis and treatment of venous thromboembolic disease: Robin revisited.

Over a decade ago, Dr. Robin expressed concern regarding overdiagnosis and overtreatment of pulmonary embolism. Since that time, significant advances have been forthcoming in the diagnosis and treatment of venous thromboembolic disease. Using Continuous Quality Improvement concepts, this study revisits Robin's concerns and assesses the conformance of clinical practice at one institution with established requirements for the diagnosis and treatment of venous thromboembolic disease to identify remaining opportunities to improve care. The study design is a retrospective chart review. Medical records of all patients (N = 63) discharged from a university-affiliated teaching hospital from 7/1/89 to 6/30/90 with a diagnosis of primary venous thromboembolic disease were studied. Requirements for the diagnosis and treatment were established through review of the medical literature. Conformance to these requirements was assessed and described. Descriptive statistics were used. Only 7 of 63 charts (11%) met all requirements for the diagnosis and treatment of venous thromboembolic disease. Fifty-six charts (89%) failed to meet at least one criterion. There was no evidence of overdiagnosis of venous thromboembolic disease in patients with a discharge diagnosis of pulmonary embolism (N = 17). Eight of 62 patients (13%) demonstrated potential overdiagnosis of venous thromboembolic disease involving the lower extremities. Nine of 60 (15%) heparin therapies demonstrated significant nonconformance to recommendations. Fifty-four of 59 (91%) warfarin therapies failed to conform to recommendations. Eighty-three percent of these warfarin errors were considered to be technical. However, 17% were determined to be clinically significant. Of 5 patients treated with a transvenous filter device, 1 failed to meet therapeutic requirements. No patients received thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

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

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

Aged↗
PubMed2001

Anticardiolipin antibodies and risk of thromboembolic disease in young Jamaican women.

BACKGROUND: Anticardiolipin antibodies (aCL) are a heterogeneous group of antiphospholipid antibodies that are associated with arterial and venous thrombosis. We measured aCL in women, aged 15-49 years, to determine if they are an independent risk factor for thromboembolic disease. STUDY DESIGN: Case--control study METHODS: Fifty cases were studied including venous thromboembolism (n=29), stroke and myocardial infarction (n=21), along with 148 age-matched controls. Serum samples were assayed for aCL and anti-beta2 glycoprotein 1 antibodies using the enzyme-linked immunosorbent assay (ELISA). Information on other risk factors was obtained by a standardized questionnaire. RESULTS: aCL were present in 16/50 (32%) of cases compared with 25/148 (17%) of controls (P[?]=[?]0.02). Unadjusted odds ratio (OR) and 95% confidence interval (95% CI) for thromboembolic disease associated with aCL was 2.32 (1.10--4.87). Other risk factors were hypertension, 2.93 (1.20--7.17) and a history of other heart diseases, 12.78 (1.32--123.60). Adjustment for hypertension, diabetes, oral contraceptive use, smoking, alcohol use, varicose veins, a family history of cardiovascular disease and a history of other heart diseases yielded OR (95%CI) 2.99 (1.32--6.80). beta2 glycoprotein 1-dependent aCL were also an independent risk factor, OR 4.56 (1.76--17.83). Subgroup analysis was carried out separately for cases of MI and stroke and for venous thrombosis. Adjusted OR (95% CI) associated with aCL in cases of MI and stroke was 1.76 (0.46--6.73) and 3.32 (1.15--9.54) for venous thromboembolism. CONCLUSION: aCL are a risk factor for thromboembolic disease in young Jamaican women. They confer a strong independent risk for venous thromboembolism.

Adolescent↗
PubMed2000

Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature.

PURPOSE: To evaluate the risk of major thromboembolic complications in male germ cell cancer patients receiving cisplatin-based chemotherapy and to review the literature on this subject. PATIENTS AND METHODS: One hundred seventy-nine germ cell cancer patients treated between January 1979 and May 1997 in our hospital were analyzed with respect to risk factors for developing thromboembolic events, such as baseline tumor characteristics, prior tumor therapy, administration of cytostatic agents, and the use of antiemetic drugs. The patients were treated with a variety of combination chemotherapy regimens, primarily cisplatin-containing combination regimens. RESULTS: Of the 179 patients, 15 patients (8.4%) were identified who developed a total of 18 major thromboembolic complications in the time period between the start of chemotherapy and 6 weeks after administration of the last cytostatic drug in first-line treatment. Of these 18 events, three (16.7%) were arterial events, including two cerebral ischemic strokes, and 15 (83. 3%) were venous thromboembolic events, including 11 pulmonary embolisms. One (5.6%) of the 18 events was fatal. Liver metastases (odds ratio, 4.9; 95% confidence interval, 1.1 to 20.8) and the administration of high doses of corticosteroids (>/= 80 mg dexamethasone per cycle; odds ratio, 3.5; 95% confidence interval, 1. 2 to 10.3) as antiemetic therapy were identified as risk factors for the development of major thromboembolic complications. CONCLUSION: Germ cell cancer patients who receive chemotherapy, in particular those who have liver metastases or receive high doses of corticosteroids, are at considerable risk of developing thromboembolic complications.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Strategies for the management of intraprocedural thromboembolic complications with abciximab (ReoPro).

OBJECTIVE: Most complications related to endovascular neurointerventional procedures are thromboembolic. The objective of this study was to determine whether abciximab, a glycoprotein IIb/IIIa inhibitor, is a safe and effective agent for the treatment of thromboembolic complications encountered during interventional neuroradiological procedures. METHODS: A search of a prospectively maintained database identified 13 patients who were treated for intraprocedural thromboembolic complications with abciximab, either alone or in combination with tissue plasminogen activator, during a 22-month period. RESULTS: Of the 13 patients in our series (10 with aneurysms, 3 with arteriovenous malformations), 12 presented with unsecured vascular lesions, and in 9 cases the lesions were either acutely (<10 d) or subacutely (<6 mo) hemorrhagic. After the identification of a thromboembolic complication, each patient was treated with either intra-arterial (n = 5) or intravenous (n = 8) abciximab. Abciximab was administered intravenously as a 0.25-mg/kg bolus (n = 2), a 0.25-mg/kg bolus followed by a 12-hour 0.125-microg/kg/min infusion (n = 5), or a 12-hour 0.125-microg/kg/min infusion alone (n = 1). Intra-arterial abciximab (3.5-10 mg) was administered directly through a microcatheter positioned in the vicinity of the thrombus (n = 5). Five patients also were administered alteplase. Complete (n = 7) or partial (n = 6) resolution of thrombus was observed in all cases. Five patients had small infarcts in the distribution of the thromboembolic complication. In no case was new or increased hemorrhaging observed after thrombolysis. CONCLUSION: Abciximab (ReoPro), administered either intravenously or intra-arterially, is a viable option for the management of thromboembolic complications encountered during endovascular therapeutic procedures.

Abciximab↗
PubMed2003

Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines.

To assess the contribution of antipsychotic medication in Japanese patients suffering acute massive pulmonary thromboembolism, records of patients with idiopathic pulmonary thromboembolism associated with antipsychotic medication who were seen in a Japanese Emergency Center from January 1996 to December 2000 were reviewed. Age, gender, physical status, clinical presentation, antiphospholipid antibody, outcome, psychiatric profile, and antipsychotic medication use were examined. Seven patients had acute pulmonary thromboembolism associated with antipsychotic drug use, representing 44% of all patients with idiopathic pulmonary thromboembolism. The 7 patients developed symptoms in the early morning. More women than men were affected. In 5 cases, chlorpromazine and other phenothiazines had been prescribed, whereas in 2 cases, risperidone, a mixed serotonin 5HT(2A) and dopamine D(2) receptor antagonist, had been taken for 40 days and 6 days, respectively. In 4 cases, including the patients taking risperidone, antiphospholipid antibodies were not present. Although statistically significant conclusions can not be drawn from this study, the data suggest that patients receiving risperidone, as well as conventional phenothiazines, are at risk for acute pulmonary thromboembolism, even if otherwise healthy. Strong affinity for the 5HT(2A) receptor of the novel antipsychotic may increase coagulability and the risk of thromboembolism.

Adult↗
PubMed1998

Thromboembolic complication in atrial fibrillation in a long-term follow-up--the relationship with underlying disease, type of atrial fibrillation, and antithrombotic therapy.

The incidence of thromboembolic complications among 288 patients with atrial fibrillation (AF) who were followed up during an average period of 7.2 years was examined retrospectively. The annual incidence of thromboembolic complications was 1.6% in total, 1.7% in valvular heart disease (n=128), and 2.1% in non-valvular heart disease (n=117). No thromboembolism occurred in lone AF (n=43), defined as the complete absence of any underlying disease. The type of AF before embolic attack was chronic in 26 cases and paroxysmal in 6 cases. The cardiac rhythm at the time of the embolic attack was AF, except in 2 cases in which ECG was not recorded. In all patients with thromboembolic complications who were receiving antithrombotic therapy during the follow-up, the anticoagulant effect just before the embolic attack was found to be insufficient. Major bleeding was not observed in the patients receiving antithrombotic therapy. Thromboembolism in AF in long-term follow-up tends to occur more frequently in patients with underlying heart disease and in those with chronic AF compared rather than paroxysmal AF; it rarely occurs in lone AF. We should not hesitate to administer sufficient anticoagulant therapy in AF patients who are at high risk of developing thromboembolic complications.

Adult↗
PubMed2001

Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation.

To determine whether treatment with antiarrhythmic drugs could be cost-effective in preventing thromboembolic events in patients with paroxysmal atrial fibrillation (AF), 4 groups of patients without prior thromboembolism were studied. Group A: 193 patients with paroxysmal AF receiving antiarrhythmic drugs, but not antiplatelets or warfarin; Group B: 228 patients with paroxysmal AF not receiving antiarrhythmics, antiplatelets or warfarin; Group C: 284 patients with chronic AF receiving warfarin; Group D: 394 patients with chronic AF not receiving antiplatelets or warfarin. Direct costs for treatment of AF were determined. During a follow-up period of 4.6 years, the prevalence of thromboembolic episodes was lower by 70% in Group A and by 47% in Group C than in each control group. To prevent one thromboembolic event annually with antiarrhythmic drugs in patients with paroxysmal AF, an extra cost of 6.16 million yen was required. This less favorable cost-effectiveness was mainly because of physician's preference for new antiarrhythmic drugs. In contrast, treatment with warfarin required an extra cost of 1.09 million yen to prevent one thromboembolic event annually in patients with chronic AF. Antiarrhythmic drugs are less cost-effective in preventing thromboembolic events in patients with paroxysmal AF when new, expensive drugs are preferentially selected.

Anti-Arrhythmia Agents↗
PubMed1997

Symptomatic venous thromboembolism after total knee replacement.

Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis. We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis. One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40). Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.

Aged↗
PubMed2006

Fondaparinux for thromboembolic treatment and prophylaxis of heparin-induced thrombocytopenia.

OBJECTIVE: To review literature evaluating the use of fondaparinux for thromboembolic treatment and prophylaxis in patients with heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted using the search terms fondaparinux, heparin, low-molecular-weight heparin, and thrombocytopenia to identify English-language articles. Additional sources were identified from bibliographies of select articles and the manufacturer. DATA SYNTHESIS: Fondaparinux, a pentasaccharide that selectively inhibits factor Xa, has been reported to have negligible or no cross-reactivity in vitro with HIT antibodies. Thromboembolic treatment and prophylaxis with fondaparinux in patients with HIT has been described. Three cases reported patients who were successfully treated for thromboembolic events with fondaparinux after developing HIT during therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Another report showed positive outcomes using fondaparinux for prophylaxis in a patient who had previously developed HIT after receiving UFH. Moreover, 2 case series, one using fondaparinux for prophylaxis in patients with a previous diagnosis of HIT and the other using fondaparinux for treatment in patients who developed HIT while receiving UFH or LMWH, reported normal platelet counts during fondaparinux treatment. Finally, results of a retrospective review demonstrated that fondaparinux prevented thromboembolic events or recurrent thrombocytopenia in patients with a prior HIT diagnosis. CONCLUSIONS: Limited data support the use of fondaparinux for thromboembolic treatment or prophylaxis in patients with antibody assay-confirmed HIT who do not have a contraindication for fondaparinux use. Randomized controlled trials have not been published; therefore, questions remain regarding efficacy, safety, optimal doses, treatment duration, and incidence of thromboembolic events when fondaparinux is used in this setting. Prospective trials evaluating the efficacy and safety of fondaparinux in this patient population need to be conducted to answer these questions.

Anticoagulants↗