Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

Evaluation of the use of venous thromboembolism prophylaxis in hospitalised medical patients.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis is effective in the prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in medical patients. METHODS: A retrospective chart review was performed on medical inpatients at two academic hospitals in Hamilton, Ontario to investigate if patients received VTE prophylaxis as per current guidelines. RESULTS: An analysis was performed on 762 patient charts and 170 met inclusion criteria for use of pharmacological VTE prophylaxis. Of these, 91 (54%) received pharmacological VTE prophylaxis. In 63 patients with a contraindication to pharmacological VTE prophylaxis, 16 (25%) received non-pharmacological VTE prophylaxis. CONCLUSION: The provision rate of pharmacological VTE prophylaxis in hospitalised medical patients who met pre-defined clinical criteria for prophylaxis was 54%. The rate of prophylaxis increased with additional VTE risk factors to a peak rate of 67%. There is room for the development of strategies to improve the use of VTE prophylaxis in hospitalised medical patients.

Information needs of adult patients 50 or older with newly diagnosed acute myeloid leukemia.

When faced with a life-threatening illness such as acute myeloid leukemia (AML), patients may feel overwhelmed with making treatment decisions. We recruited 31 consecutive English-speaking patients aged > or = 50 with newly diagnosed AML. We explored patient information needs, decision-making roles, and perceptions about prognosis. Most patients felt that they had enough information about the diagnosis and treatment options and that the doctor spent the right amount of time with them. The majority of patients preferred a passive or collaborative decision-making role. Almost half the patients did not know their estimated 6-month prognosis, and 17% felt it was 90% or better.

Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society.

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

The rational clinical examination. Is this patient having a myocardial infarction?

When faced with a patient with acute chest pain, clinicians must distinguish myocardial infarction (MI) from all other causes of acute chest pain. If MI is suspected, current therapeutic practice includes deciding whether to administer thrombolysis or primary percutaneous transluminal coronary angioplasty and whether to admit patients to a coronary care unit. The former decision is based on electrocardiographic (ECG) changes, including ST-segment elevation or left bundle-branch block, the latter on the likelihood of the patient's having unstable high-risk ischemia or MI without ECG changes. Despite advances in investigative modalities, a focused history and physical examination followed by an ECG remain the key tools for the diagnosis of MI. The most powerful features that increase the probability of MI, and their associated likelihood ratios (LRs), are new ST-segment elevation (LR range, 5.7-53.9); new Q wave (LR range, 5.3-24.8); chest pain radiating to both the left and right arm simultaneously (LR, 7.1); presence of a third heart sound (LR, 3.2); and hypotension (LR, 3.1). The most powerful features that decrease the probability of MI are a normal ECG result (LR range, 0.1-0.3), pleuritic chest pain (LR, 0.2), chest pain reproduced by palpation (LR range, 0.2-0.4), sharp or stabbing chest pain (LR, 0.3), and positional chest pain (LR, 0.3). Computer-derived algorithms that depend on clinical examination and ECG findings might improve the classification of patients according to the probability that an MI is causing their chest pain.

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Outcome of patients discharged from a coronary care unit with a diagnosis of "chest pain not yet diagnosed".

OBJECTIVE: To determine the outcome and 3-year mortality rate among patients discharged from a coronary care unit (CCU) with a diagnosis of "chest pain not yet diagnosed." DESIGN: Prospective observational cohort study. SETTING: CCU in a university teaching hospital. PATIENTS: All 158 eligible patients discharged from the CCU between August 1986 and December 1988. Of them, 27 refused to participate and 31 did not meet the inclusion criteria because of significant co-morbidity or transportation difficulties. INTERVENTIONS: Evaluation with maximal and thallium exercise stress testing and four major gastrointestinal (GI) investigations: 24-hour intraesophageal pH monitoring, upper GI endoscopy with biopsy, esophageal motility studies and an upper GI barium series. OUTCOME MEASURES: Results of investigations and incidence of recurrent chest pain, CCU readmission, coronary angiography, coronary artery bypass surgery, myocardial infarction and death at 6, 12, 24 and 36 months after the index visit. RESULTS: Of the patients enrolled in the study 79% (79/100) had a normal exercise thallium stress test result, 74% (68/92) had an abnormal result from the 24-hour pH monitoring, 87% (82/94) had abnormal endoscopic results, 90% (84/93) had abnormal manometric results, and 89% (83/93) had signs of reflux with the barium series. At 3 years 50 patients had recurrent chest pain and 3 underwent coronary artery bypass surgery. Three patients died over the 3 years, all of noncardiac causes. CONCLUSION: Many patients discharged from the CCU with a diagnosis of chest pain not yet diagnosed have a high incidence of esophageal disorders and a very low 3-year mortality rate. More research into the early and effective identification and management of patients with such a diagnosis is needed.

Evaluation of a soluble fibrin assay in patients with suspected pulmonary embolism.

In order to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with suspected pulmonary embolism (PE), 195 unselected patients with suspected PE underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for PE. A soluble fibrin result of < or = 0.75 micrograms/ml showed a sensitivity of 100% for PE and a specificity of 12.8%, whereas a soluble fibrin result of < or = 1.35 micrograms/ml showed a sensitivity of 90.3% and a specificity of 49.4% for PE. The soluble fibrin assay has potential clinical utility in excluding PE.

Evaluation of a soluble fibrin assay in patients with suspected deep vein thrombosis.

BACKGROUND: The objective of this study was to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml showed a specificity and positive predictive value of 100% for DVT. CONCLUSIONS: This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Pre-operative plasma levels of thrombin-antithrombin III complexes correlate with the development of venous thrombosis after major hip or knee surgery.

STUDY OBJECTIVE: To determine whether levels of thrombin-antithrombin III (TAT) in plasma, taken two weeks pre-operatively, predict the development of deep vein thrombosis (DVT) in patients undergoing major hip or knee surgery. DESIGN: Prospective cohort. SETTING: Tertiary-care referral centre, university-affiliated hospital. PATIENTS: Ninety eight consecutive patients undergoing elective hip or knee surgery. INTERVENTION: All eligible consenting patients were seen in a preoperative clinic two weeks prior to surgery and had blood taken for measurement of plasma TAT level. After surgery, they received a combination of unfractionated heparin 5000 Units 12-hourly subcutaneously, and antiembolism stockings (TEDS), as prophylaxis against DVT. Contrast venography was performed prior to discharge, and according to the results, patients were classified as having proximal (popliteal and/or more proximal) DVT (n = 12), calf DVT (n = 7) or no DVT (n = 79). MEASUREMENTS AND RESULTS: The mean TAT level was significantly higher in patients who developed DVT (5.7 micrograms/l) than in those who did not (4.1 micrograms/l), p = 0.035. Using cut-points of 3.5 and 5.5 micrograms/l for the TAT level, patients could be categorized as high, intermediate, and low risk for the development of DVT. The proportion of patients with TAT levels of > or = 3.5 micrograms/l who developed calf or proximal DVT was significantly higher than the proportion of patients with TAT levels of < 3.5 micrograms/l who developed calf or proximal DVT (p = 0.02). The proportion of patients with TAT levels > 5.5 micrograms/l who developed proximal DVT was significantly higher than the proportion of patients with TAT levels of < or = 5.5 micrograms/l who developed proximal DVT (p = 0.03). CONCLUSIONS: This study demonstrates that pre-operative TAT levels correlate with the risk of developing DVT after major orthopedic surgery. Further studies are needed to determine the reason(s) for this observation and whether rational recommendations about prophylaxis and screening for DVT can be made based on the results of a preoperative TAT level.

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.

Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism.

STUDY OBJECTIVE: To determine the clinical utility of a novel whole blood assay for D-dimer (SimpliRED) in patients with clinically suspected pulmonary embolism (PE). DESIGN: Prospective cohort. PATIENTS: Eighty-six consecutive patients with clinically suspected PE. INTERVENTION: All patients had the SimpliRED D-dimer assay performed and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in two patients. Patients were classified as: 1) PE-positive; positive pulmonary angiography or high probability V/Q scan or non-high probability V/Q scan and either abnormal IPG (either at presentation or upon serial testing and confirmed by contrast venography) or symptomatic thromboembolic event within three months of presentation or 2) PE-negative; normal V/Q scan or normal pulmonary angiography or non-high probability V/Q scan and normal serial IPG and absence of symptomatic venous thromboembolism within three months of follow up. Sixteen (19%) patients were classified as PE-positive and 70 (81%) patients were classified as PE-negative. MEASUREMENTS AND RESULT: The sensitivities, specificities, positive predictive values, and negative predictive values of the D-dimer assay were calculated for all patients and for the subgroup of patients without comorbid conditions that independently can cause elevated D-dimer levels. The D-dimer showed a sensitivity of 94%, a negative predictive value of 98%, a specificity of 66%, and a positive predictive value of 38%. In the subgroup of patients without comorbid conditions, the specificity increased to 98% and the positive predictive value to 83%, but because only six patients had an abnormal D-dimer level, the 95% confidence interval on the observed positive predictive value is wide (36-100%). CONCLUSIONS: This study demonstrates that the SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within five minutes, has potential clinical utility as an exclusionary test in patients with clinically suspected PE. 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.

Reevaluation of the sensitivity of impedance plethysmography for the detection of proximal deep vein thrombosis.

BACKGROUND: To reevaluate the sensitivity of impedance plethysmography (IPG) for proximal deep vein thrombosis (DVT) and to establish a relationship between the location and size of thrombi and the results of IPG. DESIGN: Prospective cohort study. METHODS: One hundred thirty-two consecutive patients with clinically suspected DVT underwent IPG testing and most (n = 118) underwent contrast-enhanced venography; in 14 patients, venous ultrasonography was performed and demonstrated definitive proximal DVT in which the size and extent of the thrombus could be delineated. All patients with dubious or normal ultrasound results underwent contrast-enhanced venography. All tests were performed and test results were interpreted without knowledge of the results of the other tests. Patients were considered to have proximal DVT if this was demonstrated on venography or ultrasound, calf DVT if this was demonstrated on venography, or no DVT if venography yielded normal findings. The sensitivity and specificity of IPG for DVT were calculated. RESULTS: Of the 132 patients, 40 (30%) had proximal DVT, seven (5%) had calf DVT, and 85 (64%) had no DVT. The sensitivity of IPG for proximal DVT was 65% and the specificity was 93%. Of the proximal vein thrombi, IPG detected three (23%) of 13 that involved the popliteal vein but not the superficial femoral vein and 23 (85%) of 27 proximal vein thrombi that involved the superficial femoral vein. CONCLUSIONS: Our study demonstrated that the sensitivity of IPG for proximal DVT at our center is only 65%, a figure that is much lower than those reported in earlier studies from our institution. We hypothesize that because of a change in referral practice, an increased proportion of patients with less severe symptoms are now referred to our center than in the past. These patients have thrombi that are smaller, less likely to be occlusive, and therefore less likely to yield abnormal IPG findings.

A noninvasive strategy for the treatment of patients with suspected pulmonary embolism.

BACKGROUND: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with non-high probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. METHODS: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. RESULTS: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. CONCLUSIONS: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients.

D-dimer in patients with clinically suspected pulmonary embolism.

STUDY OBJECTIVE: To determine whether measurement of D-dimer, using an enzyme-linked immunosorbent assay (ELISA) with a cutoff of 300 ng/ml, and a latex agglutination assay with a cutoff of 500 ng/ml, is clinically useful in patients with suspected pulmonary embolism (PE). DESIGN: Prospective cohort. SETTING: Tertiary care referral center, university-affiliated hospital. PATIENTS: Two hundred twenty-one consecutive patients with clinically suspected PE. INTERVENTION: All patients had blood drawn to measure levels of D-dimer and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in nine patients. Patients were classified as follows: (1) PE-positive; positive pulmonary angiography or high probability V/Q scan or non-high-probability V/Q scan and either abnormal IPG (either at presentation or on serial testing and confirmed by contrast venography) or symptomatic thromboembolic event within 3 months of presentation; or (2) PE-negative; normal V/Q scan or normal pulmonary angiography or non-high-probability V/Q scan and either normal serial IPG or abnormal IPG with normal venography and absence of symptomatic venous thromboembolism within 3 months of followup. Forty-three patients were classified as PE positive and 178 patients were classified as PE negative. MEASUREMENTS AND RESULTS: The sensitivities, specificities, positive predictive values, and negative predictive values of the ELISA and latex agglutination assay were calculated for all patients and for the subgroup of patients with non-high-probability V/Q scans. The ELISA D-dimer, using a cutoff of 300 ng/ml, showed a sensitivity and negative predictive value of 100 percent in all patients and patients with non-high-probability V/Q scans, but the corresponding specificities were only 26 percent and 13 percent, respectively. The latex agglutination assay for D-dimer using a cutoff of 500 ng/ml showed the following: sensitivities of 84 percent in all patients and 90 percent in patients with non-high-probability scans, negative predictive values of 93 percent in all patients, and 98 percent in patients with non-high-probability scans and specificities of 56 percent in all patients and 55 percent in patients with non-high-probability scans. CONCLUSIONS: This study demonstrates that an ELISA D-dimer result of less than 300 ng/ml excludes PE but occurs in a small proportion of patients with clinically suspected PE. The latex agglutination assay, using a cutoff of 500 ng/ml, has potential clinical utility in excluding PE in the subgroup of patients with clinically suspected PE and non-high-probability V/Q scans. However, the 95 percent confidence interval on the observed sensitivity of the latex agglutination assay in patients with non-high-probability V/Q scans is wide. Therefore, these promising results should be confirmed in a large clinical trial before the latex agglutination assay is used to make management decisions.

Deep venous thrombosis as a cause of stump swelling in two lower extremity amputee patients.

Two patients who were initially treated for an infection as a cause for their swollen stump were subsequently found to have deep venous thrombosis. The diagnosis was made noninvasively by compressive ultrasound (CU) scanning. DVT should be considered in the different diagnosis of stump swelling in the otherwise stable, post-rehabilitated lower extremity amputee patient.

Optimal therapeutic level of heparin therapy in patients with venous thrombosis.

BACKGROUND: Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. OBJECTIVES: The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. METHODS: We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. RESULTS: Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. CONCLUSIONS: Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism.