Thromb Haemostasis
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Randomized Controlled Trial Clinical Trial
Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis.
Drotrecogin alfa (activated) improved survival in patients with severe sepsis in PROWESS, a double-blind, study of 1690 adult patients randomized to drotrecogin alfa (activated) at 24 microg/kg/h (N=850) or placebo (N=840) infused for 96 hours. Pharmacodynamic effects of drotrecogin alfa (activated) were assessed with 15 prospectively defined systemic biomarkers of hemostasis, inflammation and endothelial injury. The last-observation-carried-forward (LOCF) method of imputation for missing observations was the prospectively defined statistical method. ⋯ However, the present results using different statistical methods do not provide a strong basis for systemic anti-inflammatory or pro-fibrinolytic effects. These latter two effects may occur at the local or cellular level. The systemic biomarkers reported here might not be the most appropriate approach to demonstrate these potential effects of drotrecogin alfa (activated).
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In patients with acute pulmonary embolism (PE), pulmonary occlusion rate is directly related to D-dimer and inversely related to fibrinogen levels. The role of coagulation factor XIII (FXIII) levels in acute venous thromboembolism is not known. A total of 120 consecutive patients with suspected PE and VIDAS D-dimer levels >500 micro g/L were investigated by helical computed tomography (CT). ⋯ The higher the clot burden within the pulmonary arteries the lower the FXIII antigen. In these patients, direct relation of FXIII A-subunit to fibrinogen levels argues for significant consumption of these coagulation factors in PE. This consumption of FXIII can also be detected by a global coagulation test like TEG.
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There have been no comprehensive studies that have compared the incidence of symptomatic VTE over a spectrum of different urgent or elective surgical procedures. In this study we determined the incidence of symptomatic venous thromboembolic events (VTE) within a 3 month period after 76 different surgical procedures. Using a large administrative data-base, we analyzed 1,653,275 cases that underwent one of 76 selected surgical procedures between January 1, 1992 and September 30, 1996. ⋯ Fifty-six percent of all VTE events diagnosed within 91 days of surgery occurred after discharge. The findings of this study provide a basis for categorizing different surgical procedures as low, intermediate, high and very high risk for VTE. Because of the high incidence of VTE diagnosed after hospital discharge, further studies of extended thromboprophylaxis appear warranted.
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In a retrospective study of 190 women with a first history of venous thromboembolism during pregnancy and the puerperium and 190 age-matched women with at least one prior pregnancy and no history of venous thromboembolism, the individual probability of thrombosis was determined. Assuming an overall risk of 1 in 1500 pregnancies, the probability of pregnancy-related thrombosis in carriers of homozygous factor V Leiden was 1 in 80 (odds ratio 20.6, p=0.005) and among carriers of combined heterozygous factor V Leiden and heterozygous G20210A mutation in the prothrombin gene 1 in 20 (odds ratio 88, p<0.001). The probability of thrombosis per pregnancy among women with elevated levels of factor VIII:C (>172 % activity) was 1 in 385 (odds ratio 4.5, p<0.001) and among those with increased levels of von Willebrand factor antigen (>190 %) 1 in 435 (odds ratio 4.0, p=0.002), independent of elevated factor VIII:C levels. The high prevalence of combined and homozygous defects of hemostatic components (21.6%) in patients as compared with normal women (0.86%) supports the concept that venous thromboembolism is a multicausal disorder.