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Summary. Background: Clinicians often deviate from the recommended algorithm for the diagnosis of pulmonary embolism consisting of ventilation-perfusion scintigraphy and pulmonary angiography. Objectives: To assess the safety and feasibility of a diagnostic algorithm which reduces the need for lung scintigraphy and avoids the use of angiography. Patients and methods: Consecutive patients with a clinical suspicion of pulmonary embolism were prospectively investigated according to an algorithm in which the diagnosis of pulmonary embolism was excluded after a low clinical probability estimate and a normal D-dimer test result, a normal perfusion scintigraphy result, or a non-high probability scintigraphy result in combination with normal serial ultrasonography of the legs. In these patients anticoagulant treatment was withheld and they were followed up for 3 months to record possible thromboembolic events. During the study period, 923 consecutive patients were seen, of whom 292 were excluded because of predefined criteria. Results: Of the 631 included patients, the diagnosis was refuted on the basis of a low clinical probability estimate and a normal D-dimer test result (95 patients), normal perfusion scintigraphy (161 patients) and non-high probability lung scintigraphy followed by normal serial ultrasonography (210 patients). Of these 466 patients, venous thromboembolic complications during follow-up occurred in six (complication rate 1.3%, 95% confidence interval 0.5, 2.8). The diagnostic protocol was completed in 92% of all included patients. Conclusion: The diagnosis of pulmonary embolism can be safely ruled out by a non-invasive algorithm consisting of D-dimer testing combined with a clinical probability estimate, lung scintigraphy, or serial ultrasonography of the legs (in case of non-diagnostic lung scintigraphy).

OBJECTIVE -Type 2 diabetes is associated with increased plasma concentrations of coagulation and inflammation markers. Different studies have shown that treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) is associated with antithrombotic and antiinflammatory effects in addition to a cholesterol-lowering effect. Our objective was to evaluate the effect of pravastatin (40 mg/day) on coagulation and inflammation markers in type 2 diabetic patients. RESEARCH DESIGN AND METHODS -This was an open, randomized, crossover study designed with an 8-week intervention period. The study group was comprised of 50 patients with type 2 diabetes (median HbA 1c 7.1%) and serum total cholesterol of 5-10 mmol/l. We evaluated plasma levels of fibrinogen, F1 ϩ 2, D-dimer, soluble tissue factor (sTF), von Willebrand Factor antigen (vWFag), and C-reactive protein (CRP) in blood samples drawn after fasting on day 1 and after 8 and 16 weeks.RESULTS -Significant reductions of total cholesterol (Ϫ22%; P Ͻ 0.001), LDL cholesterol (Ϫ32%; P Ͻ 0.001), and triglycerides (Ϫ10%; P Ͻ 0.05) were achieved after 8 weeks of treatment with pravastatin. In addition, significant reductions of plasma levels of F1 ϩ 2 (Ϫ4.4%; P Ͻ 0.05), vWFag (Ϫ5.3%; P Ͻ 0.05), and sTF (Ϫ3.4%; P Ͻ 0.05) were observed after treatment with pravastatin. Furthermore, plasma levels of CRP were also significantly reduced (Ϫ13%; P Ͻ 0.05). Levels of fibrinogen and D-dimer did not decrease after treatment with pravastatin.CONCLUSIONS -The results indicated that pravastatin reduces levels of coagulation and inflammation markers in type 2 diabetic patients. These antithrombotic and anti-inflammatory effects of treatment with statins could play a role in reducing cardiovascular complications in type 2 diabetic patients. Diabetes Care 27:468 -473, 2004T ype 2 diabetes is a leading cause of vascular morbidity and death. It is often complicated by other cardiovascular risk factors such as hypercholesterolemia, hypertension, obesity, and increased markers of coagulation (1) and inflammation (2). It has therefore been recommended that therapeutic prevention of cardiovascular disease in type 2 diabetes focus not only on optimal regulation of hyperglycemia but also on treatment of other cardiovascular risk factors (3,4).A subgroup analysis of several large randomized clinical trials (5,6) shows that the relative risk for cardiovascular complications in type 2 diabetic patients can be reduced by 25% using aggressive treatment of dyslipidemia with hydroxymethylglutaryl-CoA reductase inhibitors, also known as statins. Treatment with statins may be beneficial not only because of these agents' lipid-lowering action, but also because of their effect on inflammation, endothelial function, adhesion of leukocytes to endothelium, and thrombus formation (7). Although statins have proven to be effective in the prevention of cardiovascular disease in type 2 diabetes, little is known about these socalled pleiotropic effects in patients with type 2 diabetes.Our objective was to determi...

Summary. Background: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. Methods: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. Results: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) ¼ 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogenprogestin HRT was associated with a greater than 2-fold increased risk for DVT (OR ¼ 2.70; 95% CI 1.44, 5.07). Conclusion:The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Summary. Objective: In vitro studies suggest an influence of hyperhomocysteinemia on the coagulation system, but the influence of mild hyperhomocysteinemia in vivo is unclear. Methods and results:We studied the relation between homocysteine and markers of coagulation activation and endothelial cell activation in 279 patients with established atherosclerotic disease. In addition, we performed an investigator-blinded placebo-controlled cross-over study to investigate the influence of acute hyperhomocysteinemia by oral methionine load on these markers in 20 healthy volunteers. In the atherosclerotic patients prothrombin fragment F1+2 and soluble thrombomodulin (sTM) were associated with homocysteine in univariate analyses (P ¼ 0.003 and P ¼ 0.001, respectively), but not in multivariate analyses. Age, creatinine and MTHFR C677T polymorphism were major determinants of homocysteine concentration. MTHFR C677T polymorphism status was not associated with F1+2 and sTM. Median homocysteine concentrations increased in the healthy volunteers after methione load. However, after methionine load or after placebo, we did not observe different plasma concentrations of, P ¼ 0.63) and von Willebrand factor (103% vs. 107%, P ¼ 1.00). Conclusion: These results provide evidence against a major effect of mild hyperhomocysteinemia on activation of the coagulation system and endothelial cell activation in vivo.