Seminars in thrombosis and hemostasis
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Surgical patients represent a unique group of patients where therapeutic approaches can be preemptively administered. Pharmacologic strategies to prevent or decrease perioperative bleeding function to attenuate inflammatory responses, reduce hemostatic activation, or provide prohemostatic effects to reduce bleeding and the need for allogeneic transfusions. This article will discuss pharmacologic prohemostatic agents (antifibrinolytics, protamine, desmopressin, fibrinogen, purified protein concentrates, recombinant factor VIIa).
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Semin. Thromb. Hemost. · Jul 2008
ReviewThe role of natural anticoagulants in the pathogenesis and management of systemic activation of coagulation and inflammation in critically ill patients.
Critically ill patients often have systemic activation of both inflammatory systems and coagulation. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation and coagulation considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may have major consequences for the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. ⋯ Activated coagulation proteases, such as the tissue factor-factor VIIa complex, factor Xa, and thrombin, can bind to protease-activated receptors on various cells, and the ensuing intracellular signaling leads to increased production of proinflammatory cytokines and chemokines. Activated protein C can bind to the protein C receptor on endothelial cells and mononuclear cells, thereby affecting NF-kappaB nuclear translocation and subsequently influencing inflammatory gene expression and inhibition of tissue factor expression on mononuclear cells. Observations in experimental models of targeted disruption of the protein C gene and restoration of the downregulated protein C pathway by administration of recombinant activated protein C support this notion.
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Semin. Thromb. Hemost. · Apr 2008
ReviewMorbidity and mortality in the catastrophic antiphospholipid syndrome: pathophysiology, causes of death, and prognostic factors.
The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastrophic APS is not completely understood. ⋯ Cerebral involvement has been identified as the main cause of death, being present in one third of patients, and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed by cardiac involvement and infection. The only identified prognostic factor for a higher mortality rate is the presence of systemic lupus erythematosus.
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Semin. Thromb. Hemost. · Feb 2008
ReviewA critical review on the use of recombinant factor VIIa in life-threatening obstetric postpartum hemorrhage.
The objective of this review was to evaluate and summarize the current literature on the unlicensed use of the novel agent recombinant activated factor VII (rFVIIa) in the management of major postpartum hemorrhage. After a systematic electronic search without temporal limits on MEDLINE, EMBASE, OVID and SCOPUS, the bibliographic references of all retrieved studies and reviews were additionally assessed for further reports of clinical trials. Unpublished works were also identified by searching abstracts from the most eminent conferences on this topic. ⋯ Based on the evidence from the literature, we give some recommendations on the use of rFVIIa in massive postpartum hemorrhage. Nevertheless, although these reports suggest the potential role of rFVIIa in treating massive postpartum hemorrhage refractory to standard therapy, we advise particular caution in interpreting these results, as they are derived from few and uncontrolled studies. Further evidence is needed using well-designed clinical trials to better assess the optimal dose, the effectiveness, and the safety of rFVIIa in such critical bleeding conditions.
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Semin. Thromb. Hemost. · Feb 2008
ReviewCurrent and future prospects for anticoagulant therapy: inhibitors of factor Xa and factor IIa.
Indirect systemic and direct oral factor Xa and direct oral factor IIa inhibitors with improved pharmacologic profiles compared with heparins and vitamin K antagonists are currently in clinical development. This overview focuses on the indirect antithrombin dependent pentasaccharide derivatives of idraparinux and on the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran). Specifically, the results of dose-finding studies for the prevention of venous thromboembolism after elective orthopedic surgery, the results of dose-finding studies for treatment of acute venous thromboembolism including prolonged prophylaxis of recurrent events, and the designs of ongoing clinical trials are reviewed.