Coagulation proteins factor VIII

Factor VIII Coagulation proteins hemophilia A treatment 300 3 X 10- ... 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

Hemophilia A and B are coagulation disorders that result from defects in the genes encoding for plasma coagulation proteins. Hemophilia A (classic hemophilia) is caused by the deficiency of factor VIII, and hemophilia B (Christmas disease) is caused by the deficiency of factor IX. The incidences of hemophilia A and B are estimated at 1 in 5000 and 1 in 30,000 male births, respectively. Both types of hemophilia are evenly distributed across all ethnic and racial groups.1... 

Hematologic and coagulation factors Factor VIII, human recombinant glycosylated protein, produced in CHO cells ReFacto Lyophilized 250,500, or lOOOIU/vial IV... 

Vasopressin activates two subtypes of G protein-coupled receptors (see Chapter 17). Vi receptors are found on vascular smooth muscle cells and mediate vasoconstriction. V2 receptors are found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting tubules. Extrarenal V2-like receptors regulate the release of coagulation factor VIII and von Willebrand factor. 

The first therapeutic recombinant DNA-derived coagulation protein licensed by the FDA was factor VIII for treatment of hemophilia A in 1992 [38]. This step forward was a landmark in hemophilia therapy. This biotechnology process reduced the theoretical risk of human-derived viruses and seemed to provide for an unlimited market supply although other human and animal proteins were often used in the manufacturing and formulation of many recombinant... 

The third class consists of proteins that are composed of one or more BCB domains fused to a sequence domain(s) characteristic of evolutionarily unrelated protein families. Such a mosaic domain organization has been found in the phytocyanin protein family, stellacyanins, uclacyanins, and the recently characterized dicyanins (Section V) in blood coagulation factor VIII (Section VIII) and in nitrous oxide reductase (Section IX). 

Coagulation protein concentrates became available in the 1970s, a significant step in the prevention and management of bleeding. The factors that are currently available are factor VII, factor Vila, factor VIII, factor IX, factor XI, and factor XIII. There is also a factor VIII inhibitor bypassing factor, activated prothrombin... 

Patients with bleeding disorders are at risk of developing antibodies against the protein that is absent, present in reduced amounts, or present in an inactive form in their blood. Such coagulation inhibitors make treatment very difficult. Inhibitors of factor VIII are the most common and develop in 5-20% of patients with hemophiha A. Inhibitors of factor IX develop in 1-4% of patients with hemophilia B (3,4). Patients with factor VIII inhibitors present clinically either as high responders who show a strong anamnestic response and a sharp rise in inhibitor concentrations after exposure to factor VIII, or low responders, who show little or no anamnestic response (5). 

A (congenital or acquired) and type 1 von Willebrand disease, in which the VWF protein structure is normal but the plasma concentration is reduced (1). By contrast with conventional coagulation factor concentrates, desmopressin is cheap and is free from the risk of transmission of viral infections, which have proved such a problem in the past. It is also very useful in the treatment of carriers of hemophilia A, many of whom have significant reductions in the baseline concentration of factor VIII. By contrast, desmopressin has no effect on the concentration of factor IX, and is thus of no value in hemophilia B (Christmas disease). It is also of little value in type 2 (abnormal VWF structure) von Willebrand s disease, which accounts for about 15-20% of all cases. The administration of desmopressin to patients with type 2B von Willebrand s disease can be hazardous, as it is likely to cause thrombocytopenia (2). The use of desmopressin in bleeding disorders has been reviewed (3). Tachyphylaxis develops if desmopressin is used for prolonged periods to control bleeding disorders, because desmopressin causes release of stored factor VIII and von Willebrand factor, after which it takes time for them to accumulate again. 

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