Thromb Haemostasis
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Sepsis remains a complex syndrome associated with significant morbidity and mortality. It is now widely accepted that the pathways of inflammation, coagulation, apoptosis, and endothelial permeability are intimately linked in sepsis pathophysiology. The clinical success of activated protein C (APC), a natural anticoagulant, in reducing mortality in patients with severe sepsis has fuelled basic and preclinical research on the protective effects of this molecule. ⋯ APC is now viewed not only as an anticoagulant, but also as a cell signaling molecule that dampens the excessive or insufficiently controlled host response during sepsis. This review attempts to summarize the pleiotropic activities of APC with focus on its ability to inhibit coagulation, inflammation, apoptosis, and endothelial barrier breakdown. A comprehensive PUBMED literature review up to May 2008 was conducted.
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Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 characterized by an homology with other vitamin K-dependent factors (factor VII, IX, X, protein C). In contrast to these factors, PZ does not possess any enzymatic activity but is involved as a cofactor in the down-regulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor (ZPI). ZPI inhibits the activated factor X (FXa) on phospholipid surface. ⋯ Unexpectedly, a relationship between PZ deficiency and ischemic arterial diseases such as stroke, acute coronary syndromes or peripheral arterial disease was described but not confirmed by all studies. PZ deficiency could be also a risk factor for early fetal losses, and increases the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the various results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.
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Comparative Study Controlled Clinical Trial
Comparison of bivalirudin, enoxaparin, and unfractionated heparin in preventing cardiac catheter thrombosis. Results of an in-vitro study.
Bivalirudin, a direct thrombin inhibitor binds specifically and reversibly to both fibrin-bound and unbound thrombin. Bivalirudin is approved for use as an anticoagulant in patients undergoing percutaneous coronary intervention. The OASIS-5 trial presented a significant increase in cardiac catheter thrombosis for the pentasaccharid fondaparinux compared to enoxaparin. ⋯ In the bolus bivalirudin group the mean thrombus weight was significantly greater than in all other groups (p-value < 0.01 in all analyses). Bivalirudin given as a bolus was not sufficient to prevent cardiac catheter thrombosis in our in-vitro study. However, a continuous infusion of bivalirudin had similar anti-thrombotic efficacy compared to other treatment strategies.
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Clinical Trial
Maintained effectiveness of an electronic alert system to prevent venous thromboembolism among hospitalized patients.
Despite current guidelines, venous thromboembolism (VTE) prophylaxis is underused. Computerized programs to encourage physicians to apply thromboprophylaxis have been shown to be effective in selected populations. Our aim was to analyze the impact of the implementation of a computer-alert system for VTE risk in all hospitalized patients of a teaching hospital. ⋯ A sustained reduction of VTE during hospitalization was achieved, Odds ratio (OR): 0.53, 95% confidence interval (CI) (0.25-1.10) and OR: 0.51, 95%CI (0.24-1.05) during the first semesters of 2006 and 2007 respectively, the impact being significant (p < 0.05) among medical patients in 2007, OR: 0.36, 95%CI (0.12-0.98). The implementation of a computer-alert program helps physicians to assess each patient's thrombotic risk, leading to a better use of thromboprophylaxis, and a reduction in the incidence of VTE among hospitalized patients. For the first time, an intervention aimed to improve VTE prophylaxis shows maintained effectiveness over time.
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Laboratory testing for heparin-induced thrombocytopenia (HIT) includes the highly sensitive, though less specific, heparin/platelet factor 4 (PF4) ELISA. A confirmatory test with excess heparin is routinely performed on positive ELISA results to improve test specificity; the significance of a negative confirmatory result is unknown. The aim was firstly to evaluate the clinical utility of the PF4 ELISA confirmatory assay, secondly to examine the relationship between ELISA optical density (OD) value and clinical diagnosis of HIT, and thirdly to assess current practice at a tertiary care medical centre regarding patients with anti-heparin/PF4 antibodies. ⋯ Two confirm- patients were HIT+, one was HIT?; all had high ELISA OD values. Although confirm+ status correlated with clinical HIT, the confirmatory procedure misclassified some patients by yielding a confirm- result despite clinical HIT with high ELISA OD values. Future studies should compare higher ELISA OD values with the confirmatory procedure as strategies to improve ELISA diagnostic specificity for HIT.