Patrick Brill-Edwards

Heparin for 5 Days as Compared with 10 Days in the Initial Treatment of Proximal Venous Thrombosis

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

Safety of Withholding Heparin in Pregnant Women with a History of Venous Thromboembolism

BACKGROUND Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. METHODS We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. RESULTS Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episode of thrombosis that was associated with a temporary risk factor. Among the 51 women with abnormal laboratory results or a previous episode of idiopathic thrombosis, or both, 3 (5.9 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 1.2 to 16.2 percent). CONCLUSIONS The risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.

Sensitivity and Specificity of a Rapid Whole-Blood Assay for D-Dimer in the Diagnosis of Pulmonary Embolism

Objective testing is necessary to diagnose pulmonary embolism because clinical diagnosis alone is not accurate [1]. Diagnostic algorithms for patients with suspected pulmonary embolism usually involve ventilation-perfusion lung scanning as the initial test. If the scan is normal, pulmonary embolism is excluded; if it shows high probability, pulmonary embolism is diagnosed in most patients; and if it is nondiagnostic (also called non-high-probability, indeterminate, intermediate-probability, or low-probability), further testing is necessary [2-4]. In patients with nondiagnostic scans, who account for more than half of patients with suspected pulmonary embolism, the prevalence of pulmonary embolism is as high as 25%; thus, further investigation is necessary [2, 3]. Pulmonary angiography (the reference standard) or serial compression ultrasonography or impedance plethysmography over 14 days should be done in these patients to identify and treat those who develop proximal deep venous thrombosis [5]. However, these approaches are relatively costly, and pulmonary angiography is invasive. Accordingly, a simple test or combination of tests that could obviate the need to perform further tests in patients with nondiagnostic lung scans would be useful. Recently, high levels of d-dimer, a specific fibrin degradation product, were reported in studies of patients with deep venous thrombosis and pulmonary embolism [6-20]. The SimpliRED assay (Agen Biomedical, Ltd., Brisbane, Australia) is a whole-blood d-dimer assay that is suitable for bedside testing on both capillary and venipuncture samples and provides a result within 5 minutes, obviating the need to centrifuge blood and process plasma. Studies that we recently performed suggested that this assay reliably excludes deep venous thrombosis and pulmonary embolism when results are negative; these findings provided the impetus for the current study [17, 19, 20]. In addition, because our previous study of pulmonary embolism was relatively small [20], the results required confirmation in a larger study. To determine the sensitivity and specificity of the d-dimer assay in patients with suspected pulmonary embolism and to determine whether a negative d-dimer test result could be of value in excluding pulmonary embolism in patients with low pretest clinical probability, nondiagnostic lung scans, or both, we performed a cohort study of more than 1000 patients with suspected pulmonary embolism. Methods The study was performed from September 1993 to May 1996 and was approved by the institutional review boards of each participating hospital. Patients We included most patients from a recent management study that evaluated a standardized clinical model of pretest probability and developed a management strategy involving serial compression ultrasonography in most patients with nondiagnostic lung scans [21]. Thus, our sample comprised consecutive patients 18 years of age or older with clinically suspected acute pulmonary embolism who were referred to thromboembolism consultants at one of the participating tertiary-care hospitals: Chedoke-McMaster Hospitals and Hamilton Civic Hospitals, Hamilton, Ontario, Canada; Ottawa Civic Hospital, Ottawa, Ontario, Canada; and Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada. Patients were excluded from the study if they met any of the following criteria: 1) suspected upper-extremity deep venous thrombosis, 2) no symptoms within 48 hours of presentation, 3) treatment with anticoagulants for 72 hours or more, 4) life expectancy less than 3 months, 5) contraindication to contrast media, or 6) geographic inaccessibility. Informed consent was obtained from all patients in the study. Clinical Assessment Patients with clinically suspected pulmonary embolism were seen by a physician or nurse-practitioner (or both) on the health centers thromboembolism service. A history was taken and physical examination was done. Independent of diagnostic testing, all patients had clinical assessment of pretest probability, which was categorized as high, moderate, or low, as described elsewhere [21]. This evaluation involved assessment of 1) presenting symptoms and signs, 2) risk factors for venous thromboembolism, and 3) presence or absence of an alternative diagnosis at least as likely as pulmonary embolism. Objective Testing for Pulmonary Embolism The management approach used in the patient population is summarized in Figure 1. Ventilation-perfusion lung scanning was done in all patients within 24 hours of presentation by using a technique described elsewhere [22]. Scans were classified as normal (that is, the perfusion scan was normal), high probability (segmental or larger perfusion defects with normal ventilation) or nondiagnostic (perfusion defects not meeting criteria for a high-probability scan) [2]. All patients also had bilateral compression ultrasonography from the common femoral vein to the calf trifurcation within 24 hours of presentation, which was performed and interpreted according to a technique described elsewhere [23]. Figure 1. Diagnostic strategy. Patients with nondiagnostic lung scans, low or moderate pretest probability, and a normal initial compression ultrasonogram had repeated compression ultrasonography on days 3 to 5, 6 to 8, and 13 to 15. Anticoagulation was withheld provided that the results of compression ultrasonography remained normal. If the initial or serial ultrasonogram was abnormal, pulmonary embolism was diagnosed. Patients with nondiagnostic scans, high pretest probability, and normal initial compression ultrasonograms underwent venography; if the results of this test were normal, pulmonary angiography was done. If the perfusion lung scan was normal, compression ultrasonography was performed; if ultrasonography results were normal, no further testing was done and pulmonary embolism was considered excluded. If the results were abnormal, pulmonary embolism was diagnosed. Patients with a high-probability lung scan and a high or moderate pretest probability were considered to have pulmonary embolism regardless of compression ultrasonography results. Patients with a high-probability scan, low pretest probability, and normal initial compression ultrasonograms had venography; if venograms were normal, these patients also underwent pulmonary angiography. All patients who did not receive anticoagulants were followed-up for 3 months for the presence or absence of symptomatic venous thromboembolism by clinical evaluation. This consisted of a careful history to elicit symptoms of pulmonary embolism or deep venous thrombosis and appropriate investigation if such symptoms occurred. The final classification of patients as positive or negative for pulmonary embolism was based on a heterogeneous group of outcome measures. Patients were classified as positive if one or more of the following occurred: positive pulmonary angiogram; positive compression ultrasonogram (at any time) or positive contrast venogram; high-probability perfusion lung scan plus moderate or high pretest probability; or symptomatic, objectively confirmed venous thromboembolism during the 3-month follow-up. All other patients were classified as negative. Patients considered positive for pulmonary embolism received full-dose intravenous heparin or subcutaneous low-molecular-weight heparin followed by at least 3 months of oral anticoagulation. Patients who were considered negative for pulmonary embolism did not receive anticoagulant therapy. Measurement of D-Dimer Levels Blood was taken and processed by a research assistant for quantitation of d-dimer by the SimpliRED assay at the time of referral to the thromboembolism consultants. Results were categorized as normal or abnormal on the basis of the absence (normal) or presence (abnormal) of erythrocyte agglutination. This corresponds to the interpretation of d-dimer assay results used in our previous studies [17, 19, 20]. The method for the performance of the assay has been described comprehensively elsewhere [18]. The results of the d-dimer assay were not disclosed to caregivers and were obtained independently of the pretest probability assessment and results of other diagnostic tests. This assay has been shown to have excellent interobserver agreement ( = 0.95 [95% CI, 0.88 to 1.0]), between-assay agreement ( = 0.96 [CI, 0.90 to 1.0]), and reproducibility (97%) [24]. Statistical Analysis Negative predictive values, likelihood ratios, and posterior probabilities and their corresponding exact 95% CIs were calculated by using the binomial distribution [25]. Role of Industry Sponsor Agen Biomedical, Ltd., donated the d-dimer kits but had no role in the design or conduct of the study or the decision to submit this paper for publication. Results During the study, 1881 patients were screened for eligibility. Of these, 484 were excluded because of prolonged anticoagulant therapy (n = 158), expected survival less than 3 months (n = 89), geographic inaccessibility (n = 68), contraindication to contrast medium (n = 60), attending physician refusal (n = 57), pregnancy (n = 23), suspected upper-extremity deep venous thrombosis (n = 17), lack of acute symptoms within 72 hours (n = 7), or age younger than 18 years (n = 5). Of the 1397 eligible patients, 1250 (89%) agreed to enter the study. Of the consenting patients, 2 had inadequate lung scans, 58 could not undergo d-dimer assays because of assay unavailability, and 13 were lost to follow-up and could not be included. Therefore, 1177 patients (59% women; mean age, 53.4 years [range, 20 to 94 years]) were included in the final analysis. Of the 1177 patients, 197 (17%) were classified by the end of the study as positive for pulmonary embolism. None of the 980 patients classified as negative for pulmonary embolism after initial testing died of pulmonary embolism during follow-up. Overall, the d-dimer assay showed a sensitivity of 84.8%, a specificity of 68.4%, a likelihood r

A Novel and Rapid Whole-Blood Assay for D-Dimer in Patients With Clinically Suspected Deep Vein Thrombosis

BACKGROUND The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. CONCLUSIONS The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Use of Hirulog in the prevention of venous thrombosis after major hip or knee surgery.

BACKGROUND The study objective was to determine whether Hirulog, a direct thrombin inhibitor, has potential efficacy and safety in the prevention of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected patients undergoing major hip or knee surgery in tertiary-care, university-affiliated hospitals. METHODS AND RESULTS Subcutaneous Hirulog was initiated postoperatively. Patients were evaluated for bleeding and symptomatic pulmonary embolism, and mandatory bilateral venography was performed before discharge. Dose escalations were made on the basis of observed rates of bleeding and venous thrombosis. There were five dosage regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of which were significantly lower (P = .010 and P = .023, respectively) than the pooled rates of total (43%) and proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (< 5%) with all regimens. CONCLUSIONS This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is potentially efficacious and safe for the prevention of DVT after major hip or knee surgery.

Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus

In order to determine whether there is a relationship between acquired free protein S deficiency and increased thrombin generation, we performed a cross-sectional study of patients with systemic lupus erythematosus (SLE). Plasma samples were assayed for free protein S and were correlated to levels of prothrombin fragments (F1 + 2); an elevated level of F1 + 2 was used as a surrogate marker for a prothrombotic state. Assays for anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were performed on two separate blood samples taken at least 3 months apart in order to detect the presence of antiphospholipid antibodies. Of the 36 subjects, 9 had reduced free protein S levels compared to 0 of 21 controls (P = 0.01) and the mean free protein S level was significantly lower in the SLE population than in controls (0.30 +/- 0.08 U/mL versus 0.43 +/- 0.10 U/mL, P < 0.001). Of the 24 subjects with antiphospholipid antibodies, 9 had reduced free protein S levels, compared to 0 of 12 subjects without antiphospholipid antibodies (P = .01). The mean F1 + 2 level was significantly higher in study subjects with reduced free protein S levels than in those with normal free protein S levels (1.22 +/- 0.50 nmol/L versus 0.78 +/- 0.27 nmol/L, P = 0.05). This study confirms an association between antiphospholipid antibodies and reduced free protein S levels and demonstrates that patients with SLE and acquired free protein S deficiency generate more thrombin than patients with SLE and normal free protein S levels. Further studies are needed to determine whether the thrombotic diathesis associated with the presence of antiphospholipid antibodies is directly caused by the concomitant presence of acquired free protein S deficiency.

A Randomized Trial of Diagnostic Strategies after Normal Proximal Vein Ultrasonography for Suspected Deep Venous Thrombosis: d-Dimer Testing Compared with Repeated Ultrasonography

Context Physicians use several strategies to diagnose deep venous thrombosis (DVT). Contribution This trial randomly assigned 810 outpatients with suspected DVT and negative results on proximal vein ultrasonography to repeated ultrasonography at 1 week or d-dimer testing followed by no further tests if results were negative and venography if results were positive. Repeated ultrasonography diagnosed fewer DVTs than the d-dimer strategy (0.7% vs. 4.7%). In both groups followed for 6 months, only 1% to 2% of patients without DVT on initial testing developed symptomatic thromboembolism. Implications In patients with suspected DVT and negative results on proximal vein ultrasonography, a d-dimerbased strategy that minimizes additional assessments had similar safety to repeated ultrasonography. The Editors Venous compression ultrasonography is currently the diagnostic test of choice for suspected deep venous thrombosis (1, 2). Noncompressibility of the proximal veins is usually diagnostic for deep venous thrombosis, whereas normal compressibility reliably excludes proximal deep venous thrombosis (1). Ultrasonography of the distal (calf) deep veins is less accurate and is more difficult to perform than evaluation of the proximal veins (1). However, fewer than one fifth of symptomatic deep venous thromboses are confined to the distal veins, and these thrombi are associated with a very low risk for symptomatic pulmonary embolism unless they extend into the proximal veins (1). If distal deep venous thrombosis is going to extend into the proximal veins, this usually occurs within a week of presentation (1). Consequently, in patients with suspected deep venous thrombosis, it is safe to withhold anticoagulant therapy if results on ultrasonography of the proximal veins are normal (1). However, because 1% to 2% of patients with normal results on initial ultrasonography have thrombi that subsequently extend into the proximal veins, ultrasonography must be repeated after 1 week to detect these cases (1, 2). This management approach is costly and inconvenient and causes anxiety because of diagnostic uncertainty before repeated testing. Therefore, a test that reduces the need for repeated ultrasonography in patients who have normal results on initial ultrasonography would be valuable. d-Dimers are molecules that circulate when thrombi are broken down by the fibrinolytic system (3). Elevated levels of d-dimer usually occur in patients with deep venous thrombosis, and a normal d-dimer level can be used to exclude this diagnosis (3-8). We and other investigators have shown that a negative result on erythrocyte agglutination d-dimer test (SimpliRED, AGEN Biomedical Ltd., Brisbane, Australia) is valuable for excluding deep venous thrombosis and pulmonary embolism (3, 4, 6-11). This assay has advantages over other d-dimer tests because it can be performed at the bedside and yields a result within minutes. We hypothesized that the combination of a negative d-dimer result and a normal result on ultrasonography of the proximal veins would exclude thrombosis and obviate the need for follow-up ultrasonography after 1 week in outpatients with suspected deep venous thrombosis. We also hypothesized that, compared with routinely repeating ultrasonography after 1 week, performance of venography in those with a positive d-dimer result would reliably indicate or exclude deep venous thrombosis and result in fewer cases of symptomatic venous thromboembolism during follow-up. To test these hypotheses, we performed a randomized trial in which outpatients with suspected deep venous thrombosis who had normal results on ultrasonography of the proximal veins were managed according to the results of d-dimer testing or by routinely repeating ultrasonography after 1 week. Methods Patients Consecutive outpatients with suspected first episodes of deep venous thrombosis who were referred by primary care and hospital-based physicians to the thrombosis services of 4 university-affiliated hospitals were potentially eligible. We excluded patients if they had a life expectancy of less than 6 months, had a contraindication to venography, were receiving full-dose heparin therapy for more than 48 hours, were receiving long-term warfarin therapy, had no symptoms within 5 days of presentation, had symptoms of pulmonary embolism, or were pregnant or if geographic inaccessibility precluded follow-up visits. The institutional review boards of the participating centers approved the study, and all patients provided written informed consent. Management before Randomization All patients had compression ultrasonography of the deep veins of the symptomatic leg or legs, with examination of the common femoral, femoral, and popliteal veins (including the trifurcation of the calf veins) (1). Patients with abnormal results on ultrasonography received a diagnosis of deep venous thrombosis and were not eligible for randomization. Consenting patients with normal ultrasonography were eligible for randomization (Figures 1 and 2). Figure 1. Trial profile. Figure 2. Diagnostic algorithm and patient outcomes for all randomly assigned patients. DVT Randomization and Diagnostic Strategies A research statistician performed computer-generated randomization, stratified by clinical center, with random block sizes of 2 to 8 participants, and this allocation sequence was transferred to consecutively numbered, sealed, opaque envelopes that were distributed to the clinical centers. According to the directions contained in these envelopes, enrolled patients were allocated to a d-dimerbased diagnostic strategy or a repeated ultrasonography diagnostic strategy (Figures 1 and 2). d-DimerBased Strategy d-dimer testing was performed by 1 or 2 thrombosis service technologists or nurses at each site who had extensive previous experience with this test (4, 6, 7, 10, 12). With this d-dimer test (SimpliRED), a drop of whole blood obtained from a venipuncture or fingerstick is mixed with a test reagent for 2 minutes (13). The test reagent contains a bispecific antibody, 1 part of which binds to site 3B6/22 on the chain of the d-dimer, while the other part binds to erythrocyte membranes. In the presence of elevated d-dimer levels, the bispecific antibody induces agglutination of the patients erythrocytes. Any agglutination is considered a positive result, whereas no agglutination is considered a negative result. Patients with a negative d-dimer test result had no further diagnostic testing and were not treated with anticoagulation. Those with a positive d-dimer test result had venography performed the same day. If venography showed deep venous thrombosis, patients were treated with anticoagulants for at least 3 months. If deep venous thrombosis was not diagnosed (normal or nondiagnostic venogram), no further testing was performed and patients did not receive anticoagulant therapy. Repeated Ultrasonography Strategy All patients were scheduled to have ultrasonography of the proximal veins repeated after 1 week and did not receive anticoagulant therapy unless the second ultrasound was abnormal. Follow-up and Outcome Measures All randomly assigned patients, including those who received a diagnosis of deep venous thrombosis by venography or repeated ultrasonography, were contacted by telephone or attended the clinic after 3 and 6 months to determine whether venous thromboembolism or bleeding had developed. In addition, we alerted patients about the symptoms of deep venous thrombosis, pulmonary embolism and bleeding, and advised them to return to the hospital immediately if such symptoms occurred. We evaluated suspected deep venous thrombosis with ultrasonography of the proximal veins, followed by venography if the ultrasound was not diagnostic for thrombosis (1, 2). We initially evaluated suspected pulmonary embolism with ventilationperfusion lung scanning. If the lung scan was not diagnostic, patients underwent additional testing with bilateral ultrasonography of the proximal veins, bilateral venography, or pulmonary angiography (14). We did not use d-dimer testing to evaluate suspected deep venous thrombosis or pulmonary embolism during follow-up. Other than abnormal bleeding, we did not monitor adverse outcomes related to diagnostic testing and resultant treatment. We classifed deaths as due to pulmonary embolism (when there was substantive evidence) or another cause. A central adjudication committee, whose members were unaware of patient allocation groups, reviewed and classified information on all suspected outcome events and deaths. Subject to availability, data provided to this committee included study case report forms, clinic notes, original investigations (for example, lung scans and venograms), interpretation reports for original investigations, and autopsy reports. Statistical Analysis We based sample size on the requirement of narrow (that is, 2%) 95% CIs around the observed proportion of patients who would have symptomatic venous thromboembolism during 6 months of follow-up (the primary outcome measure) in each randomized group. On the basis of previous reports, we expected this proportion to be about 1.5% for both groups (1, 4). Originally, we planned to randomly assign 640 patients to satisfy these requirements. However, we found the prevalence of deep venous thrombosis diagnosed by initial ultrasonography to be lower than expected. Suspecting that the frequency of venous thromboembolism during follow-up might also be lower than expected, we decided to extend enrollment to 800 patients to accrue additional data that would narrow the 95% CIs associated with rates of outcome events. Our decision to increase sample size to 800 patients, which was based on feasibility considerations rather than formal statistical arguments, was made without knowledge of interim results. We considered the small group of patients who completed 3 months but not 6 months of follow-up to have adequate follow-up for inclusion in

Warfarin-Induced Skin Necrosis in 2 Patients with Protein S Deficiency: Successful Reinstatement of Warfarin Therapy

Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

Heparin and graduated compression stockings in patients undergoing fractured hip surgery.

Despite evidence that effective regimens are available for the prevention of venous thrombosis in fractured hip patients, many centers do not use prophylaxis. In order to evaluate the efficacy and safety of heparin and graduated compression stockings, we conducted a cohort study of 55 consecutive fractured hip patients treated postoperatively with heparin, 5,000 U every 12 h, and graduated compression stockings. The rates of venous thromboembolism and bleeding were compared with an historical cohort from Hamilton. Before discharge, 51 patients underwent bilateral venography. Deep venous thrombosis (DVT) occurred in 10 of the 51 patients (incidence of 20%); three had proximal DVT (incidence of proximal DVT was 6%). DVT was seen in 29 of the 63 control patients (incidence 46%); 19 had proximal DVT (incidence of proximal DVT was 30%). The differences in the rates of DVT and proximal DVT are statistically significant (p < 0.01). Bleeding occurred in one patient in the treatment group (incidence 2%) and five patients in the control group (incidence 8%). This study confirms that therapy with heparin and graduated compression stockings is effective, inexpensive, and convenient for the prevention of venous thrombosis in fractured hip patients and is associated with a low bleeding risk.

Evaluating the Performance of Academic Medical Education Administrators

Educators have devoted little attention to formal evaluation of educational administrative personnel. The authors surveyed the educational administrators working in McMaster University’s Department of Medicine residency program and found they felt they were receiving little useful feedback. The authors also surveyed the colleagues, residents, and administrative staff with whom the administrators worked and found they felt they had inadequate input into the administrators’ evaluation. In response to these results, a measurement instrument was developed based on existing job descriptions and feedback was obtained on administrators’ performance from relevant individuals. After three yearly evaluations, administrators and evaluators acknowledged much broader input into evaluation but saw little evaluation related improvement in performance. Of the administrators, 85% felt the process should continue as did 91% of the evaluators. An evaluation process may not alter perceived performance when it is already good but there may be other benefits to rigorous evaluation.