Potential role of recombinant FVII as a hemostatic agent
Recombinant factor VIIa (rFVIIa) has been shown to induce hemostasis in hemophilia patients with inhibitors against factor VIII or factor IX independent of factor VIII/factor IX. Factor VIIa binds to tissue factor (TF) exposed at the site of injury and generates, through factor X activation on the TF-bearing cells, enough thrombin to activate factors VIII, V, and XI, as well as platelets. The thrombin-activated platelets provided a perfect template for binding of activated factors VIII, IX, and V, further activation of factor X, and thrombin generation. Factor VIIa in high concentrations binds to thrombin-activated platelets and is capable of activating factor X, thereby generating thrombin independent of the presence of factor VIII or factor IX. Accordingly, rFVIIa has been shown to initiate hemostasis in severe hemophilila patients with inhibitors subjected to major surgery and suffering from serious limb- and life-threatening bleeding. Since rFVIIa enhances thrombin generation-thereby providing the formation of tight, stable fibrin hemostatic plugs resistance to premature lysis-it should be hemostatic in other situations characterized by impaired thrombin generation. A hemostatic effect has been reported in patients with various platelet disorders and factor XI deficiency. Further, a hemostatic effect of rFVIIa has been reported in patients subjected to trauma and extensive surgery who have developed profuse, excessive bleeding resulting in hemodilution and changes in coagulation patterns. rFVIIa was developed to treat bleeding in hemophilia patients with inhibitors against factor VIII or factor IX and has been shown to induce effective hemostasis in most such patients and also in life- and limb-threatening bleeding. It has also been used successfully to stop bleeding in patients who do not have hemophilia but who do have acquired antibodies against factor VIII (acquired hemophilia). rFVIIa initiates hemostasis by forming a complex with TF exposed as a result of vessel wall injury. Pharmacologic doses of rFVIIa can enhance thrombin generation on platelets that are already thrombin-activated, resulting in the formation of full thrombin burst. By enhancing thrombin generation, rFVIIa helps to form tight, stable, fibrin plugs resistant to premature fibrinolysis. This also maintains hemostasis in the absence of factor VIII or factor IX. Pharmacologic doses of rFVIIa may accordingly be of benefit in producing hemostasis in situations other than hemophilia characterized by profuse bleeding and impaired thrombin generation. There is now clinical experience indicating a hemostatic effect in patients with thrombocytopenia and functional platelet defects. rFVIIa has also been successfully used in acute trauma patients with profuse bleedings and in other bleeding situations.
Available from: dunkanesthesia.info
- "Prothrombin complex concentrates that contain Factors II, IX, X, and VII have also been shown to be effective . Recombinant Factor VIIa (rFVIIa) (NovoSeven) may be used in patients who have congenital or acquired hemophilia, and those in whom inhibiting antibodies toward Factors VIII or IX have formed    . In such patients , where there is risk of death caused by uncontrollable bleeding during emergency surgery or in limb-threatening hemorrhages such as hemarthroses and muscle hematomas, treatment should be aimed at bypassing inadequate levels of Factors VIII and IX and the other factors contained in the intrinsic pathway, and should instead rely upon rFVIIa infusions to bind directly or in conjunction with tissue factor to negatively charged phospholipids exposed on the surface of activated platelets  . "
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ABSTRACT: The present understanding of the coagulation process emphasizes the final common pathway and the proteolytic systems that result in the degradation of formed clots and the prevention of unwanted clot formations, as well as a variety of defense systems that include tissue repair, autoimmune processes, arteriosclerosis, tumor growth, the spread of metastases, and defense systems against micro-organisms. This article discusses diagnosis and management of some of the most common bleeding disorders. The goals are to provide a simple guide on how best to manage patients afflicted with congenital or acquired clotting abnormalities during the perioperative period, present a brief overview of the methods of testing and monitoring the coagulation defects, and discuss the appropriate pharmacologic or blood component therapies for each disease.
Available from: Frank Giles
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ABSTRACT: Gemtuzumab ozogamicin (GO) is a chemotherapeutic agent that consists of a humanized anti-CD33 antibody (hP67.6) linked to N-acetyl-gamma calicheamicin 1,2-dimethyl hydrazine dichloride, a potent enediyne antitumor antibiotic. GO was approved conditionally by the Federal Drug Administration in May 2000 as single-agent therapy for first recurrence of acute myeloid leukemia (AML) in a subset of older patients. Data on studies in AML with GO-based regimens have been reported rapidly in addition to new observations on the target antigen, CD33. These data indicate promising new areas of investigation with GO, including its application as maintenance therapy in patients with AML and as an induction and/or maintenance agent in patients with acute promyelocytic leukemia;, and they also have highlighted challenges in the development of GO, particularly its association with hepatic venoocclusive disease. In vitro data on the mechanism of action of GO may be particularly helpful in the design of future clinical studies.
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ABSTRACT: The revised model of coagulation has implications for therapy of both hemorrhagic and thrombotic disorders. Of particular interest to anesthesiologists is the management of clotting abnormalities before, during, and after surgery. Most hereditary and acquired coagulation factor deficiencies can be managed by specific replacement therapy using clotting factor concentrates. Specific guidelines have also been developed for perioperative management of patients using anticoagulant agents that inhibit platelet or coagulation factor functions. Finally, recombinant factor VIIa has been used off-label as a hemostatic agent in some surgical situations associated with excessive bleeding that is not responsive to conventional therapy.
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