Recurrence of venous thromboembolism in patients with familial thrombophilia

BACKGROUND: Treatment of patients with deep vein thrombosis and an antithrombin or protein C or S deficiency is based on case reports and personal experience. OBJECTIVE: To systematically assess the risk for recurrence of venous thromboembolism after a first episode in patients with these deficiencies, a literature review and retrospective family cohort study were performed. METHODS: For the literature review, the annual incidence of a first recurrent venous thromboembolism was assessed for each deficiency by dividing the number of venous thromboembolic events by the number of years at risk. For the family cohort study, 1- and 5-year cumulative incidences of first recurrence were calculated based on medical histories taken in relatives of consecutive patients in whom venous thromboembolism and a deficiency were diagnosed. RESULTS: For the literature review, the annual incidence of a first recurrent venous thromboembolism in patients with antithrombin or protein S deficiency ranged from 13% to 17% and 14% to 16%, respectively. For the family cohort study, the 1- and 5-year cumulative incidences of recurrent venous thromboembolism were 10% (95% confidence interval, 1%-19%) and 23% (95% confidence interval, 10%-36%), respectively. Warfarin sodium (Coumadin) prophylaxis was associated with 2 venous thromboembolic events in 141 years at risk (1.4% per year), in contrast with 19 events in 709 years at risk (2.7% per year) without prophylaxis (difference, -1.3%; 95% confidence interval, -3.5% to 1.0%). CONCLUSIONS: The annual incidence of recurrent venous thromboembolism is high during the first years following a first episode, but seems to decline thereafter. Therefore, our results challenge current practice of prescribing lifelong warfarin therapy after a first or second episode of venous thromboembolism in patients with antithrombin or protein C or S deficiency.     

Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism

OBJECTIVE: To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism. METHODS: A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention. RESULTS: The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%). CONCLUSION: A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice.     

Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations

OBJECTIVE: This study's objective was to evaluate the association between venous thromboembolism during pregnancy and the postpartum period and the factor V Arg 506 Gln (factor V Leiden), the prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphisms. STUDY DESIGN: In this case-control study 42 case patients and 213 control subjects (parous age-matched women without history of thrombosis) were genotyped for all the polymorphisms. Moreover, antiphospholipid antibodies and protein C, protein S, and antithrombin III deficiencies were investigated in each case. RESULTS: Ten case patients (23.8%) and 4 control subjects (1.9%; odds ratio 16.3, 95% confidence interval 4.8-54.9) carried the factor V Leiden mutation; 13 case patients (31.0%) and 9 control subjects (4.2%; odds ratio 10.2, 95% confidence interval 4.0-25.9) were carriers of the prothrombin G20210A allele. Finally, 12 case patients (28.6%) and 34 control subjects (16.0%; odds ratio 2.1, 95% confidence interval 1.0-4.5) were homozygotes for methylenetetrahydrofolate reductase C677T. Overall, mutations were found in 25 case patients (59.5%) and 47 control patients (22.2%; odds ratio 5.2, 95% confidence interval 4.9-19.6). One patient carried the antithrombin III deficiency and 1 the protein S deficiency, whereas 2 women had a primary antiphospholipid syndrome. CONCLUSIONS: The significant risk estimates of having a pregnancy-related venous thromboembolism in the presence of the prothrombotic genetic risk factors analyzed suggest to screen for these mutations women with a personal history of thromboembolic events during pregnancy or the postpartum period.     

Coronary angioplasty volume-outcome relationships for hospitals and cardiologists

OBJECTIVE: To assess the relationship between each of 2 provider volume measures (annual hospital volume and annual cardiologist volume) for percutaneous transluminal coronary angioplasty (PTCA) and 2 outcomes of PTCA (in-hospital mortality and same-stay coronary artery bypass graft [CABG] surgery). DESIGN: Cohort study, using data from January 1, 1991, through December 31, 1994, from the Coronary Angioplasty Reporting System of the New York State Department of Health. SETTING: Thirty-one hospitals in New York State in which PTCA was performed during 1991-1994. PATIENTS: All 62670 patients discharged after undergoing PTCA in these hospitals during 1991-1994. MAIN OUTCOME MEASURES: Rates of in-hospital mortality and CABG surgery during the same stay as the PTCA. RESULTS: The overall in-hospital mortality rate for patients undergoing PTCA in New York during 1991-1994 was 0.90%, and the same-stay CABG surgery rate was 3.43%. Patients undergoing PTCA in hospitals with annual PTCA volumes less than 600 experienced a significantly higher risk-adjusted in-hospital mortality rate of 0.96% (95% confidence interval [CI], 0.91%-1.01%) and risk-adjusted same-stay CABG surgery rate of 3.92% (95% CI, 3.76%-4.08%). Patients undergoing PTCA by cardiologists with annual PTCA volumes less than 75 had mortality rates of 1.03% (95% CI, 0.91%-1.17%) and same-stay CABG surgery rates of 3.93% (95% CI, 3.65%-4.24%); both of these rates were also significantly higher than the rates for all patients. Also, same-stay CABG surgery rates for patients undergoing PTCA in hospitals with annual volumes of 600 to 999 performed by cardiologists with annual volumes of 75 to 174 (2.99%; 95% CI, 2.69%-3.31 %) and 175 or more (2.84%; 95% CI, 2.57%-3.14%) were significantly lower than the overall statewide rate (3.43%). CONCLUSIONS: In New York State, both hospital PTCA volume and cardiologist PTCA volume are significantly inversely related to in-hospital mortality rate and same-stay CABG surgery rate for patients undergoing PTCA.     

Physician-guided treatment compared with a heparin protocol for deep vein thrombosis

BACKGROUND: Effective heparin therapy, defined by therapeutic prolongation of the activated partial thromboplastin time (APTT), decreases the risk of recurrent venous thromboembolism. Achieving therapeutic prolongation of the APTT within 24 hours of the start of heparin therapy has proved difficult. We hypothesized that a protocol that delivered high initial heparin infusions to patients without identifiable risk for bleeding complications would decrease the time to achieve a therapeutic anticoagulant effect without increasing the incidence of major bleeding complications. METHODS: To test this hypothesis, we studied concurrent patient cohorts. We defined a therapeutic anticoagulant effect (APTT > 55 seconds) to be an APTT more than 1.5 times the upper limit of normal. Twenty patients with acute symptomatic deep vein thrombosis received a 5000-U heparin bolus, followed by 1680 U/h (low risk to bleed) or 1240 U/h (high risk to bleed), adjusted by protocol-directed response to APTT results. Forty-eight patients with deep vein thrombosis were treated by their physicians. The Kaplan-Meier method was used to examine the proportion of patients who achieved an APTT greater than 55 seconds as a function of time. RESULTS: The two study cohorts did not differ with respect to age, weight, or risk factors for venous thromboembolism. Analysis of Kaplan-Meier curves showed that the heparin protocol decreased the time to achieve a therapeutic anticoagulant effect (P = .025). Ten (91%) of 11 patients (95% confidence interval, 59% to 100%) without risks to bleed who were treated by the heparin protocol and 29 (60%) of 48 patients (95% confidence interval, 45% to 74%) not treated by the protocol had an initial therapeutic APTT (P = .006). CONCLUSION: A protocol that delivers higher initial heparin infusions to patients without identifiable risks for bleeding decreases the time needed to achieve therapeutic prolongation of APTT, when compared with nonprotocol physician management.     

Prophylaxis for venous thromboembolism in head and neck surgery: the practice of otolaryngologists

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are an important cause of morbidity and mortality in the surgical patient. The first guideline produced by the Scottish Intercollegiate Guidelines Network was for the prophylaxis of venous thromboembolism. Patients undergoing major head and neck cancer surgery commonly exhibit risk factors for venous thromboembolism. Currently, however, there are no data on its incidence in these patients. A questionnaire survey was performed to assess the current practice of consultant otolaryngologists regarding DVT prophylaxis in patients undergoing head and neck cancer surgery. Of those respondents who managed these patients, 57 per cent did not use routine DVT prophylaxis while 43 per cent did. A wide variety of techniques were employed among those practising DVT prophylaxis. A consensus is needed concerning the use of thromboembolism prophylaxis in head and neck surgery patients.     

Access and outcomes of elderly patients enrolled in managed care

OBJECTIVE: To determine differences in access to care and medical outcomes for Medicare patients with an acute or a chronic symptom who were enrolled in health maintenance organizations (HMOs) compared with similar fee-for-service (FFS) nonenrollees. DESIGN: A 1990 household telephone survey of Medicare beneficiaries who reported joint pain or chest pain during the previous 12 months. SAMPLE: Stratified random sample of HMO enrollees (n = 6476) and comparable sample of FFS Medicare beneficiaries (n = 6381). ACCESS AND OUTCOME MEASURES: Care-seeking behavior, physician visits, diagnostic procedures performed, therapeutic interventions prescribed, follow-up recommended by a physician, and symptom response to treatment. RESULTS: After controlling for demographic factors, health and functional status, and health behavior characteristics, HMO enrollees with joint pain (n = 2243) were more likely than nonenrollees (n = 2009) to have a physician visit (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.03 to 1.38) and medication prescribed (OR, 1.35; 95% CI, 1.14 to 1.60). Patients with chest pain who were enrolled in HMOs (n = 556) were less likely than nonenrollees (n = 524) to have a physician visit (OR, 0.50; 95% CI, 0.30 to 0.82). For both joint and chest pain, HMO enrollees were less likely to see a specialist for care, have follow-up recommended, or have their progress monitored. There were no differences in complete elimination of symptoms, but HMO enrollees with continued joint pain reported less symptomatic improvement than nonenrollees (OR, 0.72; 95% CI, 0.59 to 0.86). CONCLUSIONS: Reduced utilization of services for patients with specific ambulatory conditions was observed in HMOs with Medicare risk contracts, with less symptomatic improvement in one of the four outcomes studied.     

Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians

BACKGROUND: Both cardiologists and generalist physicians care for patients with acute myocardial infarction, but little is known about their patients' characteristics, treatments, and outcomes. METHODS: We identified attending and consulting physicians, patient characteristics, drugs, procedures, and mortality from clinical and administrative records of 1620 Medicare beneficiaries aged 65 to 79 years who were treated for acute myocardial infarction at 285 hospitals in Texas during 1990. RESULTS: Patients treated by attending cardiologists were younger, had prior congestive heart failure less frequently, and were initially treated in hospitals offering coronary angioplasty or bypass surgery more often than patients treated by attending generalist physicians (for each, P<.004). Adjusting for patient and hospital characteristics, cardiologists were more likely than generalist physicians to prescribe thrombolytic therapy and aspirin (P<.05) but not beta-adrenergic blocking agents (beta-blockers). Cardiologists used coronary angiography and angioplasty more often (P<.003), but not echocardiography or exercise testing. Adjusted 1-year mortality did not differ significantly between patients of attending cardiologists and generalist physicians (odds ratio, 1.01; 95% confidence interval, 0.76-1.35) or between patients of generalist physicians with and without a consulting cardiologist (odds ratio, 0.83; 95% confidence interval, 0.60-1.16). However, patients initially admitted to hospitals offering coronary angioplasty and bypass surgery had lower adjusted 1-year mortality than patients admitted to other hospitals (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). CONCLUSIONS: Compared with generalist physicians, cardiologists used some, but not all, effective drugs more frequently, as well as coronary angiography and angioplasty. Although these differences were not associated with lower adjusted mortality among cardiologists' patients, cardiologists were more likely to treat patients in hospitals with better outcomes. Future studies should identify organizational factors that improve outcomes of myocardial infarction.     

Risk of venous thromboembolism and stroke associated with oral contraceptives. Role of congenital thrombophilias

To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P < 0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P < 0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.     

Relationship between physician and hospital coronary angioplasty volume and outcome in elderly patients

BACKGROUND: With the expectation that physicians who perform larger numbers of coronary angioplasty procedures will have better outcomes, the American College of Cardiology/ American Heart Association guidelines recommend minimum physician volumes of 75 procedures per year. However, there is little empirical data to support this recommendation. METHODS AND RESULTS: We examined in-hospital bypass surgery and death after angioplasty according to 1992 physician and hospital Medicare procedure volume. In 1992, 6115 physicians performed angioplasty on 97,478 Medicare patients at 984 hospitals. The median numbers of procedures performed per physician and per hospital were 13 (interquartile range, 5 to 25) and 98 (interquartile range, 40 to 181), respectively. With the assumption that Medicare patients composed one half to one third of all patients undergoing angioplasty, these median values are consistent with an overall physician volume of 26 to 39 cases per year and an overall hospital volume of 196 to 294 cases per year. After adjusting for age, sex, race, acute myocardial infarction, and comorbidity, low-volume physicians were associated with higher rates of bypass surgery (P < .001) and low-volume hospitals were associated with higher rates of bypass surgery and death (P < .001). Improving outcomes were seen up to threshold values of 75 Medicare cases per physician and 200 Medicare cases per hospital. CONCLUSIONS: More than 50% of physicians and 25% of hospitals performing coronary angioplasty in 1992 were unlikely to have met the minimum volume guidelines first published in 1988, and these patients had worse outcomes. While more recent data are required to determine whether the same relationships persist after the introduction of newer technologies, this study suggests that adherence to minimum volume standards by physicians and hospitals will lead to better outcomes for elderly patients undergoing coronary angioplasty.     

Health status of persons with acute radiation sickness caused by Chernobyl AES accident

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.     

Indications, outcomes, and provider volumes for carotid endarterectomy

CONTEXT: While trials have demonstrated that carotid endarterectomy is superior to best medical therapy, most recently among asymptomatic patients, uses and outcomes of the procedure in more representative settings have not been established. OBJECTIVES: To profile the use and outcomes of carotid endarterectomy in a representative sample of Ohio's Medicare beneficiaries and to examine the relationships between provider-specific procedural volumes and patient outcomes. DESIGN: Retrospective cohort using Medicare Provider Analysis and Review files supplemented by detailed reviews of medical records on a random sample of patients. SETTING: Ohio hospitals performing carotid endarterectomy. PATIENTS: A random sample of 678 charts of the 4120 non-health maintenance organization Medicare beneficiaries who underwent carotid endarterectomy between July 1, 1993, and June 30, 1994. MAIN OUTCOME MEASURES: Nonfatal stroke or death within 30 days of surgery. RESULTS: The reviewed patients were similar to all eligible patients in sociodemographic characteristics and 30-day mortality rates. Among the 678 patients, indications for surgery were asymptomatic carotid stenosis in 167 (24.6%), transient ischemic attack in 294 (43.4%), completed stroke in 62 (9.1%), and nonspecific symptoms in 155 (22.9%). Thirty-two patients (4.7%) died or suffered nonfatal strokes by 30 days postoperatively. In univariate analyses, rates varied by hospital volume (P=.004) but not surgeons' volume (P=.47), although power to detect this difference was limited. Patients at higher- and lower-volume hospitals had similar indications and distributions of comorbidities. In analyses controlling for indications, comorbid conditions, and surgeon's volume, being operated on in a higher-volume hospital conferred a 71% reduction in risk for 30-day stroke or death (odds ratio, 0.29; 95% confidence interval, 0.12-0.69; P=.006). CONCLUSIONS: Almost half (47.5%) of the carotid endarterectomies among Ohio's Medicare population are performed on persons who are asymptomatic or who have nonspecific symptoms. These results highlight the importance of identifying patients and providers having the most favorable outcome profiles. The higher rate of adverse outcomes observed in lower-volume hospitals deserves further investigation, as it does not appear to be due to differences in patient selection.     

Diagnostic value of compression ultrasonography and fibrinogen-related parameters for the detection of postoperative deep vein thrombosis following elective hip replacement: a pilot study

To determine their ability to diagnose postoperative deep vein thrombosis (DVT) D-dimer - by three methods -, fibrinogen degradation products (FgDP) and fibrinogen levels were measured in 68 consecutive patients before elective surgery for hip replacement and on postoperative day 1, 3, 6, and 10. All patients received prophylaxis and underwent compression real-time B-mode ultrasonography (C-US) on postoperative day 5 and 9, and bilateral ascending venography on day 10. Twenty-two out of 68 patients developed asymptomatic postoperative DVT, which was limited to the calf veins in 14 and involved the proximal veins in 8 patients. C-US was negative in all patients on day 5. On day 9, C-US sensitivity and specificity for proximal DVT were 63% (95% confidence interval: 26%-90% and 98% (89%-100%) respectively. Postoperative changes in the laboratory parameters evaluated were not different in patients with or without DVT until day 10. On day 10, mean D-dimer, FgDP and fibrinogen levels were significantly higher in patients with DVT than in those without DVT (p values between 0.006 and 0.032), but only D-dimer was higher with DVT involving two or more venous segments than with thrombosis involving one venous segment only (p < 0.05). Stepwise logistic regression analysis identified D-dimer and fibrinogen on day 10 as predictors of postoperative DVT. In a receiver operator curve and after weighing for the coefficients generated by logistic regression analysis, the combination of a latex photometric immuno-assay and of PT-derived fibrinogen yielded-at a cut-off value of 7.0 a sensitivity of 100% (73%-100%) and a specificity of 58% (39%-75%) for DVT, with a negative predictive value of 100% (78%-100%), a positive predictive value of 52% (32%-71%) and an overall accuracy of 71% (55%-83%). These results suggest that two simple, fast and reproducible tests may permit the identification of patients at low risk of having postoperative DVT and that a combination of sensitive laboratory assays and of the highly specific C-US may select patients requiring anticoagulant treatment. Efficacy and cost-effectiveness of this approach should be evaluated in large clinical management studies.     

Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.     

Abbreviated hospitalization for deep venous thrombosis with the use of ardeparin

BACKGROUND: Ardeparin sodium has recently received approval by the Food and Drug Administration for prophylaxis against venous thromboembolism in patients undergoing elective total knee replacement. However, this low-molecular-weight heparin has not been previously evaluated in a randomized controlled trial for treatment of established acute deep venous thrombosis. METHODS: The study included patients with ultrasound-documented acute symptomatic deep venous thrombosis of the legs. They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular-weight heparin. Patients were randomized to receive ardeparin with a 2-day hospitalization or unfractionated heparin sodium with a 5-day hospitalization. Both groups received warfarin sodium. Follow-up ultrasound examinations were undertaken at 6 weeks. RESULTS: Of the 80 patients enrolled, 75 had follow-up ultrasonography. Evaluation of baseline vs 6-week venous scans demonstrated that, overall, 31 of the 39 ardeparin-treated patients improved, compared with 21 of the 36 patients assigned to receive unfractionated heparin (P=.05). The 95% confidence interval for the difference in improvement was 0.6% to 42% in favor of ardeparin. Median charges for ardeparin and unfractionated heparin were $2815 and $6500, respectively (P<.001). There were no differences in bleeding or patient satisfaction between the 2 groups. CONCLUSIONS: The results of this small preliminary trial suggest that ardeparin can be administered effectively and safely to selected patients with acute deep venous thrombosis and that, with proper nursing and home services, it can help decrease the duration of hospitalization.     

Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis

OBJECTIVE: To study the incidence of late deep venous thrombosis (DVT), and to evaluate a regimen of prolonged thromboprophylaxis after general surgery. DESIGN: Randomised, controlled, open trial, with blinded evaluation. SETTING: University hospital, Denmark. SUBJECTS: 176 consecutive patients undergoing major elective abdominal or non-cardiac thoracic operations, of whom 118 were eligible for evaluation. INTERVENTIONS: Thromboprophylaxis with a low-molecular-weight heparin, tinzaparin, given for four weeks (n = 58), compared with one week (control group, n = 60). MAIN OUTCOME MEASURES: Presence of DVT established by bilateral venography four weeks after the operation. RESULTS: The incidence of late DVT in the control group was 6/60 (10%, 95% confidence interval (CI) 4% to 21%). In the prophylaxis group it was 3/58 (5.2%, 95% CI 1% to 14%) (p = 0.49). CONCLUSION: Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery.     

Hypomelanosis of Ito associated with hemimegalencephaly: a clinicopathological study

Pulmonary embolism poses a risk to patients undergoing total knee arthroplasty. The selection of an appropriate prophylaxis agent and its implementation have been influenced by decreased duration of hospital stay and the pressures of cost containment. The purpose of this study was to determine the inpatient and outpatient pulmonary embolism rates, the number of days required to attain the target level of anticoagulation, and complications associated with the use of a low-dose warfarin prophylaxis protocol after primary and revision total knee arthroplasty. Between 1984 and 1993, there were 815 primary and revision total knee arthroplasties that received low-dose warfarin prophylaxis at our institution. The average time to attainment of the target level of anticoagulation was 3 days. The average duration of warfarin prophylaxis was 12 days. Overall, there were a total of three symptomatic pulmonary embolisms (0.3%; 95% confidence interval, 0.08%-1.1%). There were eight (1%) symptomatic deep vein thromboses (all distal). There were two deaths (0.3%), but neither one was secondary to a pulmonary embolism. Seventeen knees (2.5%) developed a hematoma after surgery, and two of these patients required drainage of the knee. Low-dose warfarin prophylaxis is safe and effective in preventing symptomatic pulmonary embolism after total knee arthroplasty.     

Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.     

Angiographic embolization of intrahepatic arterioportal fistula

BACKGROUND: Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. METHODS: From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for genotyping. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. RESULTS: 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p < 0.05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% CI: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% CI: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. CONCLUSION: These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.