Is the prevalence of the factor V Leiden mutation in patients with pulmonary embolism and deep vein thrombosis really different?

INTRODUCTION: Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. METHODS: We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultrasonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. RESULTS: In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. CONCLUSION: In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.

Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism.

OBJECTIVES: To construct and validate the bleeding risk prediction score, which is based on variables identified in the literature that can be easily obtained before the institution of anticoagulant therapy, in a large independent cohort of patients who were treated with anticoagulant therapy for established venous thromboembolism to allow for quantitative assessment of the risks and benefits of the therapy and to adapt the patient's management accordingly. METHODS: We constructed a bleeding risk prediction score, based on variables and their odds ratios identified in the literature, which can be easily obtained before the institution of anticoagulant therapy (score = [ 1.6 X age] + [1.3 x sex] + [2.2 X malignancy]). Subsequently, we evaluated the score in a test group of 241 patients treated with anticoagulant therapy for venous thromboembolism to determine the optimal cutoff points for the prediction of hemorrhagic complications, using receiver operating characteristic curve analysis. We then validated this score in an independent cohort of 780 patients. A score of 3 or more points, 1 to 3 points, or 0 points represented a high, intermediate, or low bleeding risk, respectively. RESULTS: The score in about one fifth of the patients in the test group was classified as predicting high risk for bleeding complications. The risk of all bleeding complications was 26% in this group and the risk of major bleeding complications was 14%. The area under the curve was 0.75 (95% confidence interval, 0.64-0.84) and 0.82 (95% confidence interval, 0.66-0.98) for all bleeding complications and major bleeding complications, respectively. When validated, there was a moderate loss of predictive power of the score, but the categorization of the patients by the score remained clinically useful; 20% of the patients were classified as high risk, and the bleeding rate was 17% for all bleeding complications and 7% for major bleeding complications compared with 4% and 1%, respectively, in those categorized as low risk. CONCLUSIONS: With the use of 3 easily obtainable, clinical variables in a prediction model, it is possible to identify a subgroup of patients at the start of anticoagulant therapy who have a high risk of developing hemorrhagic complications. Further studies should address whether additional measures to prevent bleeding decrease the bleeding incidence without compromising efficacy.

The role of a decision rule in symptomatic pulmonary embolism patients with a non-high probability ventilation-perfusion scan.

BACKGROUND: In order to improve the use of information contained in the medical history and physical examination in patients with suspected pulmonary embolism and a non-high probability ventilation-perfusion scan, we assessed whether a simple, quantitative decision rule could be derived for the diagnosis or exclusion of pulmonary embolism. METHODS: In 140 consecutive symptomatic patients with a non-high probability ventilation-perfusion scan and an interpretable pulmonary angiogram, various clinical and lung scan items were collected prospectively and analyzed by multivariate stepwise logistic regression analysis to identify the most informative combination of items. RESULTS: The prevalence of proven pulmonary embolism in the patient population was 27.1%. A decision rule containing the presence of wheezing, previous deep venous thrombosis, recently developed or worsened cough, body temperature above 37 degrees C and multiple defects on the perfusion scan was constructed. For the rule the area under the Receiver Operating Characteristic curve was larger than that of the prior probability of pulmonary embolism as assessed by the physician at presentation (0.76 versus 0.59; p = 0.0097). At the cut-off point with the maximal positive predictive value 2% of the patients scored positive, at the cut-off point with the maximal negative predictive value pulmonary embolism could be excluded in 16% of the patients. CONCLUSIONS: We derived a simple decision rule containing 5 easily interpretable variables for the patient population specified. The optimal use of the rule appears to be in the exclusion of pulmonary embolism. Prospective validation of this rule is indicated to confirm its clinical utility.

A survey of the diagnostic and therapeutic management of patients with suspected pulmonary embolism in the Netherlands.

BACKGROUND: Pulmonary embolism (PE) remains a complex diagnostic problem. Many diagnostic modalities are available. Several published guidelines have failed to yield a uniform approach. We have assessed the current diagnostic and therapeutic management of patients with clinically suspected PE in the Netherlands. METHODS: A questionnaire was sent to internists and pulmonologists, who were then asked to detail their diagnostic and therapeutic management in their last patient seen with suspected PE. RESULTS: 1571 questionnaires were sent out (response rate 64%). 95% of the patients with suspected PE underwent a perfusion scan (in 91% within 24 h). 1.6% of the respondents had no available perfusion scan facility. Of those who underwent a perfusion scan, 62% had ventilation scan (66% with segmental defects, 80% with subsegmental defects, 27% with a normal perfusion scan). Tests for deep vein thrombosis were performed in 58% of the patients and pulmonary angiography was carried out in 6.1%. Anticoagulant treatment was instituted in 73.2% of all patients. CONCLUSIONS: The perfusion lung scan is appropriately used as the initial step in the diagnostic workup of patients with suspected PE. Ventilation scanning is overused in patients with subsegmental perfusion defects and normal scan results, whereas it is underused in patients with segmental defects. Additional ventilation scan results had a limited influence on treatment decisions. There is still considerable overtreatment of patients with suspected PE.

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

BACKGROUND: The standard diagnostic approach in patients suspected of having pulmonary embolism starts with perfusion-ventilation lung scanning. If the resulting scan is not diagnostic, pulmonary angiography should be done. The use of tests for deep venous thrombosis has been advocated as an adjunct to establishing the diagnosis of pulmonary embolism, but no prospective studies have provided adequate information about the value of these tests. OBJECTIVE: To determine the accuracy and potential clinical utility of compression ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective cohort study with blinded assessment of ultrasonographic results. SETTING: Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and specificity of compression ultrasonography. Perfusion-ventilation scanning and angiography were the conjoint gold standard for determining the presence or absence of pulmonary embolism. Also calculated were the number of angiograms and lung scans avoided and the number of patients unnecessarily treated when compression ultrasonography was included in the diagnostic strategy. RESULTS: The overall sensitivity of compression ultrasonography for deep venous thrombosis in patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was 97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before lung scanning would avoid approximately 14% of lung scans and 9% of angiograms but would lead to unnecessary treatment of 13% of patients who have an abnormal ultrasonographic result (2% to 4% of all those receiving anticoagulation). When compression ultrasonography is done only in patients with a nondiagnostic lung scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26% of patients who have an abnormal ultrasonographic result (2% of all patients receiving anticoagulation). CONCLUSION: The diagnostic value of compression ultrasonography for the detection of deep venous thrombosis in patients suspected of having pulmonary embolism is limited; the gain in diagnostic efficiency obtained through the use of ultrasonography may be offset by a loss in diagnostic accuracy.

The clinical course of patients with suspected pulmonary embolism.

BACKGROUND: The outcome of patients with suspected pulmonary embolism is known to a limited extent only. OBJECTIVE: To address this limited knowledge in a cohort in whom pulmonary embolism was proved or ruled out. METHODS: Consecutive patients with clinically suspected pulmonary embolism underwent lung scintigraphy and angiography if required. Pulmonary embolism was excluded by normal results of a lung scan or angiogram, and, if so, anticoagulant therapy was withheld. Pulmonary embolism was proved with a high-probability perfusion-ventilation lung scan or a confirmatory angiogram if a nondiagnostic lung scan was obtained. These patients were treated with heparin intravenously and anticoagulants orally on a long-term basis. All patients were followed up for 6 months, with a special focus on recurrent thromboembolism, bleeding complications, and mortality. RESULTS: A total of 487 consecutive inpatients and outpatients were included. Pulmonary embolism was excluded or proved in 243 and 193 patients, respectively. In 51 patients a definite diagnosis could not be established. The overall prevalence of pulmonary embolism was 39%. In patients in whom pulmonary embolism was proved, excluded, or uncertain, recurrent venous thromboembolism was observed in 2.6%, 0.9%, and 2%, respectively. Serious bleeding complications occurred in 7 patients (3.3%; 95% confidence interval [CI], 1.8%-6.3%), 2 cases of which were fatal. The total mortality after 6 months in patients with proved or excluded pulmonary embolism was 17% (95% CI, 12%-23%) and 11% (95% CI, 7%-15%), respectively. Death was related to (recurrent) pulmonary embolism in 5% and 0% of these cases, respectively. CONCLUSIONS: During a 6-month period, recurrent pulmonary embolism occurred in approximately 5 patients (2.5%) who were treated for a previous episode. Fatal bleeding complications attributable to the use of anticoagulants were encountered in 1%. The mortality among patients with suspected pulmonary embolism was considerable. However, most deaths were unrelated to pulmonary embolism, but were the result of serious underlying illnesses.

Aspergillus fumigatus, a rare cause of fatal coronary artery occlusion.

Endocarditis by Aspergillus species in patients without prior cardiovascular surgery is extremely rare and difficult to diagnose. We report and discuss a 69-year-old patient with hairy cell leukemia who developed severe bilateral pneumonia and metastatic subcutaneous nodules from which A. fumigatus was cultured. He died after 18 days of treatment with an adequate dose (0.7 mg/kg/day) of amphotericin B intravenously. Fungal endocarditis and a myocardial infarction due to a septic thrombotic occlusion of the left coronary artery by A. fumigatus appeared to be the cause of death. A. fumigatus could still be cultured from the aortic valve postmortem despite a total dose of 756 mg amphotericin B. In case of metastatic spread of Aspergillus spp., endocarditis should be suspected.