Hormone replacement therapy and risk for venous thromboembolism: what's new and how do these findings influence clinical practice?

PURPOSE OF REVIEW: Although an association between hormone replacement therapy and venous thromboembolism has been established, several unanswered questions remain. This review will address additional questions relating to hormone replacement therapy and venous thromboembolism. Does the risk for venous thromboembolism differ according to the type of hormone replacement therapy? Does the presence of thrombophilia influence the risk for venous thromboembolism in hormone replacement therapy users? Should hormone replacement therapy be temporarily interrupted around the time of surgery? RECENT FINDINGS: The risk for venous thromboembolism seems to be less in users of estrogen-only hormone replacement therapy (odds ratio = 1.2; 95% confidence interval: 0.6-2.6) than in users of estrogen-progestin hormone replacement therapy (odds ratio = 2.7; 95% confidence interval: 1.4-5.1), and there may be no increased risk for venous thromboembolism with transdermal hormone replacement therapy (odds ratio = 1.0; 95% confidence interval: 0.3-3.3). The presence of a prothrombotic blood abnormality, such as the factor V Leiden mutation, seems to further increase the risk for venous thromboembolism in hormone replacement therapy users (odds ratio = 17.1; 95% confidence interval: 3.7-78). Continued use of hormone replacement therapy in the perioperative period does not seem to have an impact on the overall risk for postoperative venous thromboembolism (odds ratio = 0.66; 95% confidence interval: 0.35-1.18). SUMMARY: Recent studies have extended our understanding regarding the association between hormone replacement therapy and venous thromboembolism. The implications of these findings on clinical practice are discussed.     

Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives

BACKGROUND: Conflicting data are available on air travel as a risk factor for venous thromboembolism. To our knowledge, there are no studies investigating whether individuals with thrombophilia and those taking oral contraceptives are more likely to develop venous thromboembolism during flights than those without these risk factors. PARTICIPANTS AND METHODS: The study sample consisted of 210 patients with venous thromboembolism and 210 healthy controls. DNA analysis for mutations in factor V and prothrombin genes and plasma measurements of antithrombin, protein C, protein S, total homocysteine levels, and antiphsopholipid antibodies were performed. RESULTS: In the month preceding thrombosis for patients, or the visit for controls, air travel was reported by 31 patients (15%) and 16 controls (8%), with an oddsratio of 2.1 (95% confidence interval, 1.1-4.0). Thrombophilia was present in 102 patients (49%) and 26 controls (12%), and oral contraceptives were used by 48 patients and 19 controls (61% and 27% of those of reproductive age, respectively). After stratification for the presence of air travel and thrombophilia, the odds ratio for thrombosis in individuals with both risk factors was 16.1 (95% confidence interval, 3.6-70.9). Stratification for the presence of air travel and oral contraceptive use gave an odds ratio of 13.9 (95% confidence interval, 1.7-117.5) in women with both risk factors. CONCLUSIONS: Air travel is a mild risk factor for venous thromboembolism, doubling the risk of the disease. When thrombophilia or oral contraceptive use is present, the risk increases to 16-fold and 14-fold, respectively, indicating a multiplicative interaction.     

Deep vein thrombosis in elderly patients hospitalized in subacute care facilities: a multicenter cross-sectional study of risk factors, prophylaxis, and prevalence

BACKGROUND: The efficacy of venous thromboembolism prophylaxis has not been established, to our knowledge, in elderly patients hospitalized in subacute care facilities. OBJECTIVES: To describe risk factors and physician practices in the prevention of venous thromboembolism and to estimate the prevalence of deep vein thrombosis. METHODS: A multicenter cross-sectional study was conducted in the subacute care departments of 36 French hospitals. The study population included 852 inpatients older than 64 years. Systematic ultrasound examination was performed by angiologists. RESULTS: Of the 852 inpatients, 178 (20.9%; 95% confidence interval [CI], 18.2%-23.8%) had 3 or more risk factors other than age, while 144 patients (16.9%; 95% CI, 14.4%-19.6%) had none. The rate of prophylactic anticoagulant treatment was 56.1%, ranging from 20.0% to 86.9%, depending on the department. In multivariate analysis, prophylaxis use was associated with acute immobilization (odds ratio [OR], 4.17; 95% CI, 2.48-7.01), chronic immobilization (OR, 3.19; 95% CI, 2.22-4.60), major surgical procedure (OR, 6.81; 95% CI, 4.26-10.88), and congestive heart failure (OR, 1.65; 95% CI, 1.02-2.67). Prophylaxis use was low in patients who had cancer (OR, 0.49; 95% CI, 0.29-0.84) or myocardial infarction (OR, 0.39; 95% CI, 0.14-1.00). It was not significantly associated with paralytic stroke or history of venous thromboembolism. Deep vein thrombosis was detected in 135 patients (15.8%; 95% CI, 13.4%-18.5%): 50 (5.9%; 95% CI, 4.4%-7.7%) had proximal vein thrombosis and 85 (10.0%; 95% CI, 8.0%-12.2%) had calf vein thrombosis. CONCLUSIONS: The prevalence of deep venous thrombosis is high in these patients, despite wide use of prophylaxis. Further prospective studies assessing the clinical benefit of extended duration prophylaxis are needed in elderly patients hospitalized in subacute care settings.     

Prevention of major venous thromboembolism following total hip or knee replacement: a randomized comparison of low-molecular-weight heparin with unfractionated heparin (ECHOS Trial).

AIM: Venous thromboembolism remains a frequent complication after total hip or knee replacement surgery despite routine prophylaxis. However, the ability of pharmacologic thromboprophylaxis to prevent major venous thromboembolism, defined as proximal deep vein thrombosis, and/or pulmonary embolism, and/or death, has not been previously validated. METHODS: In a double-blind randomized study, 2018 patients, undergoing either total hip or knee replacement surgery, were allocated to receive subcutaneous preoperative reviparin (4,200 anti Xa IU) once daily or 7,500 IU unfractionated heparin twice daily, for a minimum of 11 days. The primary efficacy outcome was major venous thromboembolism, defined as the composite of venographically confirmed proximal deep vein thrombosis, and/or symptomatic pulmonary embolism and death, recorded up to day 14. RESULTS: The primary efficacy outcome was assessed in 1,628 patients and demonstrated a significant reduction in the reviparin group (3.4% [28 of 813 patients] compared with unfractionated heparin (5.5% [45 of 815]) (odds ratio, 0.61; 95% confidence interval, 0.38 to 0.99, P=0.04) by day 11 to 14. A significant reduction in venous thromboembolism was maintained up to 6-8 weeks (3.4% [28 of 813 reviparin patients] versus 5.6% [46 of 815 unfractionated heparin patients]) (odds ratio, 0.6; 95% confidence interval, 0.37 to 0.97, P=0.03). Major bleeding events occurred in 9 reviparin-treated patients (0.9%) and in 12 unfractionated heparin-treated patients (1.2%). CONCLUSIONS: Prophylaxis with reviparin significantly reduces the risk of major venous thromboembolism compared with unfractionated heparin in patients undergoing elective hip or knee replacement without increasing the risk of bleeding.     

Risks of oral anticoagulant therapy with increasing age

BACKGROUND: Oral anticoagulation in the elderly is a dilemma. Although many elderly patients have strict indications for treatment with coumarin derivatives, the tendency toward an increased bleeding risk with age is a matter of concern. We investigated the risk of hemorrhage and thromboembolism according to age in patients who were treated with oral anticoagulants in the routine setting of an anticoagulation clinic. METHODS: All patients of the Leiden Anticoagulation Clinic (Leiden, the Netherlands) who were treated because of mechanical heart valve prostheses (target, international normalized ratio [INR] of 3.5), atrial fibrillation (target, INR of 3.0), or after a myocardial infarction (target, INR of 3.0) between 1994 and 1998 were included in the study and grouped by age at the start of follow-up. We calculated incidence rates of major hemorrhage and thromboembolism per age group. RESULTS: We included 4202 patients: 842 patients younger than 60 years; 1200 patients aged between 60 and 70 years; 1464 patients aged between 71 and 80 years; and 696 patients older than 80 years. The incidence rate of major hemorrhage rose gradually with age from 1.5 per 100 patient-years for patients younger than 60 years to 4.2 per 100 patient-years for patients older than 80 years, yielding a hazard ratio of 2.7 (95% confidence interval, 1.7-4.4). The incidence rate of major thromboembolism rose from 1.0 per 100 patient-years for patients younger than 60 years to 2.4 per 100 patient-years for patients older than 80 years (hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSIONS: The incidence of both bleeding and thromboembolic events increases sharply with advanced age. Because higher thromboembolic risk with age often makes it unfeasible to withhold oral anticoagulation from elderly patients, future studies should focus on ways to lower the bleeding risk.     

Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism

Allele frequencies for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene were determined in a large case-control study of 517 unselected patients with venous thromboembolism and 478 blood donors. The D allele frequency was 0. 53 [95% confidence interval (CI) 0.50-0.56] in patients and 0.54 (95% CI 0.50-0.57) in controls, giving an odds ratio for the D allele of 0.97 (95% CI 0.81-1.16). In the same population, the odds ratio for the factor V Leiden mutation (F5G1691A) was 6.9 (95% CI 4. 0-11.9). Therefore, the ACE I/D polymorphism is not a risk factor in a representative group of unselected patients with venous thromboembolism. The possibility that the I/D polymorphism is a risk factor for venous thromboembolism specifically after hip replacement cannot be excluded.     

Hyperhomocyst(e)inemia and the increased risk of venous thromboembolism: more evidence from a case-control study

BACKGROUND: Elevation of plasma homocyst(e)ine level is an independent risk factor for arterial and venous thrombosis. We studied the degree to which hyperhomocyst(e)inemia contributes to the development of venous thromboembolism, using a retrospective case-control study design. METHODS: Cases were individuals with objectively confirmed venous thromboembolism and no history of atherosclerosis seen at the Toronto Hospital Thrombosis Clinic, Toronto, Ontario, between January 1, 1996, and July 31, 1998. Three controls were matched for every case according to sex and age within 5 years and were derived from a large community cohort. All subjects underwent assessment for fasting plasma homocyst(e)ine levels. Hyperhomocyst(e)inemia was defined as a fasting total homocyst(e)ine concentration above the 95th percentile control value. RESULTS: Seventy cases and 210 matched controls were included. Men and women were equally represented, and most were younger than 60 years. Among cases with venous thromboembolism, the mean (+/- SD) plasma homocyst(e)ine level was significantly higher than in controls (13.0 +/- 6.9 micromol/L vs 9.0 +/- 4.8 micromol/L, respectively; P<.001). Sixteen (23%) of 70 cases had hyperhomocyst(e)inemia compared with 10 (5%) of 210 controls (odds ratio, 5.9; 95% confidence interval [CI], 2.5-13.8). Among subjects aged 60 years or younger, the odds ratio was 4.9 (95% CI, 1.4-16.4), while for those aged 60 years or older, it was 7.3 (95% CI, 2.2-24.0). Even with the exclusion of cases showing abnormal renal function or low serum vitamin B12 or folate levels, the odds ratio remained significantly elevated at 3.3 (95% CI, 1.1-10.0). CONCLUSIONS: We found that fasting hyperhomocyst(e)inemia is a significant risk factor for venous thromboembolic disease in patients at a thrombosis clinic. Given the magnitude of effect and consistency across these studies, it is likely that homocyst(e)ine plays a causative role in the development of venous thrombosis, and it should be considered in the workup for venous thromboembolism.     

Association of Anemia with Venous Thromboembolism in Acutely Ill Hospitalized Patients: An APEX Trial Substudy

Background

Anemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism and whether the presence of anemia can refine risk assessment for prediction of venous thromboembolism, thereby adding incremental utility to a validated model.

Sickle cell trait and the risk of venous thromboembolism among blacks

People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case-control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.     

Recurrence risk after anticoagulant treatment of limited duration for late,second venous thromboembolism

Patients with a second venous thromboembolism generally receive anticoagulant treatment indefinitely, although it is known that the recurrence risk diminishes over time while the risk of hemorrhage persists with continued anticoagulation and increases with age. Based on these arguments and limited evidence for indefinitely prolonged treatment, the Dutch guidelines recommend considering treatment of a limited duration (i.e. 12 months) for a ‘late’ second venous thromboembolism, defined by a second venous thromboembolism diagnosed more than 1 year after discontinuing treatment for a first event. It is hypothesized that the risk of continued anticoagulation might outweigh the benefits in such circumstances. We evaluated this management in daily practice. Since 2003, limited duration of treatment was systematically considered at our hospital in consecutive patients, in whom we determined the recurrence risk. Of 131 patients with late second venous thromboembolism, 77 were treated for a limited duration, of whom 26 developed a symptomatic third venous thromboembolism thereafter during a cumulative follow-up of 277 years, resulting in an incidence rate of 9.4/100 patient-years (95% confidence interval: 6.1–14). The incidence rates in patients with unprovoked and provoked venous thromboembolism were 12/100 patient-years (95% confidence interval: 7.4–19) and 5.6/100 patient-years (95% confidence interval: 2.2–12), respectively [adjusted hazard ratio 2.8 (95% confidence interval: 1.1–7.2)]. The recurrence risk after treatment of limited duration for ‘late’ second venous thromboembolism exceeded the risk of hemorrhage associated with extended anticoagulation. Most patients may, therefore, be better served by treatment of indefinite duration, although the risk-benefit ratio of extended anticoagulation should be weighed for every patient.     

Predictors and Outcomes of Recurrent Venous Thromboembolism in Elderly Patients

Background

Little is known about predictors and outcomes of recurrent venous thromboembolism in elderly patients.

Minor injuries as a risk factor for venous thrombosis

BACKGROUND: Injuries increase the risk of venous thrombosis. So far, most research has focused on major injuries that are accompanied by other risk factors for venous thrombosis, such as plaster casts and surgery. We studied the association of venous thrombosis with common minor injuries, such as minor sural muscle ruptures and ankle sprains. METHODS: We performed a large, population-based, case-control study (the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA] study), including consecutive patients with a first deep venous thrombosis of the leg or pulmonary embolism and control subjects. Participants with malignant neoplasms, those who underwent surgery, and those who had a plaster cast or extended bed rest were excluded. RESULTS: Of 2471 patients, 289 (11.7%), and of 3534 controls, 154 (4.4%) had a minor injury in the 3 months preceding the venous thrombosis (patients) or completion of the questionnaire (controls). Venous thrombosis was associated with previous minor injury (odds ratio adjusted for sex and age, 3.1; 95% confidence interval, 2.5-3.8). The association was strongest for injuries that occurred in the 4 weeks before thrombosis and was not apparent before 10 weeks. Thrombosis was more strongly associated with minor injuries located in the leg (odds ratio adjusted for sex and age, 5.1; 95% confidence interval, 3.9-6.7), while those located in other body parts were not associated. A 50-fold increased risk was found in factor V Leiden carriers with a leg injury compared with noncarriers without injury (odds ratio, 49.7; 95% confidence interval, 6.8-362.7). CONCLUSIONS: Minor injuries in the leg are associated with greater risk of venous thrombosis. Because minor injuries are common, they could be major contributors to the occurrence of venous thrombosis.     

High plasma concentration of factor VIII coagulant is also a risk factor for venous thromboembolism in the elderly

BACKGROUND AND OBJECTIVES: A high level of coagulant factor VIII is a well known risk factor for venous thromboembolism, but most studies have enrolled patients under 70 years old. This study aimed to test the hypothesis that an association also exists in the elderly. DESIGN AND METHODS: This hospital-based case-referent study took place at the Department of Internal Medicine and Chest Diseases, University Hospital, Brest, France. We enrolled 161 patients with a first episode of venous thrombosis and 239 subjects, referred for a clinical suspicion of venous thromboembolism which was subsequently ruled out. Factor VIII coagulant activity and plasma fibrinogen concentration were measured. RESULTS: High factor VIII coagulant activity was significantly associated with venous thromboembolism, irrespective of the age group. Patients over 70 years with factor VIII coagulant activity above 225% had a 2.4-fold increased risk of venous thromboembolism compared to those patients with levels below 130% (age- and fibrinogen-adjusted odds ratio: 2.6, 95% CI 1.1 to 6.1). INTERPRETATION AND CONCLUSIONS: Our results show that high levels of factor VIII coagulant, a determinant of venous thrombosis in adulthood, is also a risk factor in the elderly.     

Venous thromboembolism in travellers: can we identify those at risk?

To assess the prevalence of clinical and laboratory risk factors in patients who develop venous thromboembolism following travel. The design was a case series of 58 consecutive patients presenting with venous thromboembolism within 30 days of travel. The setting was a major metropolitan teaching hospital and an affiliated private practice. The main outcome measures were prevalence of clinical and laboratory risk factors for venous thromboembolism, time to presentation, mode and duration of travel. Forty-eight [83%; 95% confidence interval (CI), 71-91%] of 58 patients developed venous thromboembolism following air travel. Thirty-four (59%; 95% CI, 45-71%) patients had travelled for more than 8 h and most patients were diagnosed with venous thromboembolism within 1 week of completing their journey. Pulmonary embolism occurred in 24 patients (41%; 95% CI, 29-55%), proximal deep vein thrombosis in 23 patients (40%; 95% CI, 27-53%), calf vein thrombosis in four patients (7%; 95% CI, 2-17%), and superficial thrombophlebitis in seven patients (12%; 95% CI, 5-23%). At least one clinical or laboratory risk factor (other than travel) was found in 49 patients (84%; 95% CI, 73-93%) and two or more risk factors were found in 30 patients (52%; 95% CI, 38-65%). The most common risk factors were oestrogens (24%; 95% CI, 14-37%), a past history of thrombosis (24%: 95% CI, 14-37%), and factor V Leiden (24%: 95% CI, 14-37%). These retrospective uncontrolled data suggest that at least one clinical or laboratory risk factor is present prior to travel in more than 80% of patients who develop venous thromboembolism within 30 days of travel. In most cases these risk factors can be identified by the clinical history alone, without recourse to laboratory testing. Whether patients with known risk factors for venous thromboembolism prior to travel should be targeted with specific thromboprophylaxis requires randomized evaluation.     

Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial

BACKGROUND: We were concerned that a fixed rather than a weight-based dosing regimen of dalteparin sodium to prevent venous thromboembolism (VTE) might result in decreased efficacy in obese patients and decreased safety in elderly patients. METHODS: We retrospectively performed subgroup analyses using the database from the Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients (PREVENT) Trial, a study of 3706 hospitalized, medically ill patients randomized to receive either dalteparin sodium, 5000 U/d, or placebo. The primary end point was a composite of symptomatic VTE, fatal pulmonary embolism, sudden death, or asymptomatic proximal deep venous thrombosis by day 21. Obesity was defined as a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 30 or greater for men and 28.6 or greater for women. RESULTS: Overall, 1118 patients (30.4%) were obese and 1226 (33.3%) were 75 years or older. In obese patients, the primary end point occurred in 2.8% of the dalteparin and in 4.3% of the placebo groups (relative risk, 0.64; 95% confidence interval [CI], 0.32-1.28). In patients 75 years or older, the primary end point was reported in 4.2% of the dalteparin and in 8.0% of the placebo groups (relative risk, 0.52; 95% CI, 0.31-0.87). The dalteparin effect for the primary end point (odds ratio, 0.51; 95% CI, 0.32-0.82) was not attenuated when adjusted for age, sex, obesity, history of VTE, and varicose veins. Dalteparin was not associated with an increase in major hemorrhage by day 21 in obese (0% vs 0.7% placebo; P>.99) and in elderly (1.1% vs 0.7%; P=.12) patients. CONCLUSION: Our findings suggest that a fixed low dose of dalteparin sodium of 5000 U/d is effective and safe in preventing VTE in obese and elderly hospitalized medical patients.     

Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study

BACKGROUND: Reported risk factors for venous thromboembolism (VTE) vary widely, and the magnitude and independence of each are uncertain. OBJECTIVES: To identify independent risk factors for deep vein thrombosis and pulmonary embolism and to estimate the magnitude of risk for each. PATIENTS AND METHODS: We performed a population-based, nested, case-control study of 625 Olmsted County, Minnesota, patients with a first lifetime VTE diagnosed during the 15-year period from January 1, 1976, through December 31, 1990, and 625 Olmsted County patients without VTE. The 2 groups were matched on age, sex, calendar year, and medical record number. RESULTS: Independent risk factors for VTE included surgery (odds ratio [OR], 21.7; 95% confidence interval [CI], 9.4-49.9), trauma (OR, 12.7; 95% CI, 4.1-39.7), hospital or nursing home confinement (OR, 8.0; 95% CI, 4.5-14.2), malignant neoplasm with (OR, 6.5; 95% CI, 2.1-20.2) or without (OR, 4.1; 95% CI, 1.9-8.5) chemotherapy, central venous catheter or pacemaker (OR, 5.6; 95% CI, 1.6-19.6), superficial vein thrombosis (OR, 4.3; 95% CI, 1.8-10.6), and neurological disease with extremity paresis (OR, 3.0; 95% CI, 1.3-7.4). The risk associated with varicose veins diminished with age (for age 45 years: OR, 4.2; 95% CI, 1.6-11.3; for age 60 years: OR, 1.9; 95% CI, 1.0-3.6; for age 75 years: OR, 0.9; 95% CI, 0.6-1.4), while patients with liver disease had a reduced risk (OR, 0.1; 95% CI, 0.0-0.7). CONCLUSION: Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE.     

Staphylococcus aureus bacteremia among elderly vs younger adult patients: comparison of clinical features and mortality.

BACKGROUND: Previous studies give conflicting results regarding the effect of age on outcomes in Staphylococcus aureus bacteremia (SAB). These studies have been limited by retrospective design or small sample size. METHODS: We conducted a prospective cohort study of 385 patients with SAB aged 18 to 90 years. The setting was a large academic medical center. We observed patients from diagnosis of SAB to discharge or death. Discharged patients were contacted 12 weeks after their first positive culture findings. Data were collected on demographics, comorbid conditions, focus of infection, length of stay, and outcome. Primary outcomes were total mortality and death due to SAB. RESULTS: Comparisons were made between 145 patients, aged 66 to 90 years, and 240 patients, aged 18 to 60 years. Forty-three (29.7%) of the elderly patients and 36 (15%) of the younger patients died. Death directly attributable to SAB occurred in 21 (14.5%) older and 15 (6.3%) younger patients. After adjusting for confounding variables, older patients continued to have higher total mortality (odds ratio, 2.21; 95% confidence interval, 1.32-3.70), and higher mortality from SAB (odds ratio, 2.30; 95% confidence interval, 1.13-4.69). Infection with methicillin-resistant S aureus was associated with higher total mortality in the elderly (odds ratio, 2.59; 95% confidence interval, 1.23-5.43). CONCLUSIONS: Staphylococcus aureus bacteremia among the elderly is associated with high mortality. Both total mortality and mortality directly attributable to SAB are more than twice as likely in older patients. Infection with methicillin-resistant S aureus carries a worse prognosis than infection with methicillin-sensitive S aureus in the elderly.     

Study of the echocardiographic diagnosis of acute pulmonary thromboembolism and risk factors for venous thromboembolism

OBJECTIVES: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE). METHODS: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group). RESULTS: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE. CONCLUSIONS: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.     

Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study

BACKGROUND: The optimal duration of thromboprophylaxis after major orthopedic surgery is controversial. Although oral anticoagulants are still widely used for the prevention of venous thromboembolism after hip replacement, to our knowledge no study has assessed the benefit of prolonging anticoagulation beyond the hospital stay. METHODS: Consecutive patients who had received warfarin sodium prophylaxis after total hip arthroplasty were randomized to stop taking the drug at the time of hospital discharge or to continue taking it for 4 more weeks. The rate of symptomatic and asymptomatic venous thromboembolic events (as shown by compression ultrasonography of the proximal-vein system) occurring during the study period was compared between the 2 groups. The study was prematurely terminated after the inclusion of the first 360 patients because a statistically significant and clinically relevant superiority of extended over short-term thromboprophylaxis was observed. RESULTS: Objectively confirmed venous thromboembolic complications were recorded in 10 patients: 9 (5.1%) in the group of 176 control patients, and 1 (0.5%) in the group of 184 patients who continued the warfarin treatment. The absolute difference in the incidence of events was 4.57% (95% confidence interval [CI], 1.15-7.99). The relative risk of venous thromboembolism developing in control patients compared with patients assigned to extended thromboprophylaxis was 9.4 (95% CI, 1.2-73.5). The number needed to treat was 22. Major bleeding developed in 1 patient who was randomized to the extended prophylaxis group (0.5%; 95% CI, 0.02-3.0) compared with none in the control group. CONCLUSION: Extending prophylaxis with warfarin for a few more weeks beyond the hospital stay has the potential to considerably improve the outcome of patients who undergo hip arthroplasty.