Coagulation factor VIII deficiency

Replacement of deficient gene products or even of organs is also utilized in the treatment of genetic disorders for example, replacement of coagulation factor VIII in hemophilia A, of or-antitrypsin in persons deficient in this factor or of pancreatic islet cells in some forms of diabetes mellitus. 

Vandendriessche, T., Vanslembrouck, V., Goovaerts, I., Zwinnen, H., Vanderhaeghen, M. L., Collen, D. and Chuah, M. K. (1999). Long-term expression of human coagulation factor VIII and correction of hemophilia A after in vivo retroviral gene transfer in factor VUI-deficient mice. Proc. Natl. Acad. Sci. USA 96, 10379-10384. 

A revealing assay. Suppose that you have just examined ayoung hoy with a bleeding disorder highly suggestive of classic hemophilia (factor VIII deficiency). Because of the late hour, the laboratory that carries out specialized coagulation assays is closed. However, you happen to have a sample of blood from a classic hemophiliac whom you admitted to the hospital an hour earlier. What is the simplest and most rapid test that you can perform to determine whether your present patient also is deficient in factor VIII activity ... 

Before the screening of blood and plasma and before virus inactivation procedures were applied to coagulation factor products (for example factor VIII and factor IX), many hemophiliacs who were treated with substitution therapy were exposed to infection with HIV. In the USA about 70% of tested persons with hemophiha A (factor VIII deficiency) and 35% with hemophilia B (factor IX deficiency) were HIV-seropositive (177). 

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... 

The pathophysiology of hemophilia is based on the factor VIII or IX deficiency resulting in inadequate thrombin generation and an impaired intrinsic-pathway coagulation cascade (see... 

Clinical pharmacology Activated factor IX in combination with activated factor VIII activates factor X. This results ultimately in the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, and a clot can be formed. Factor IX is the specific clotting factor deficient in patients with hemophilia B and in patients with acquired factor IX deficiencies. The administration of Coagulation Factor IX (Recombinant) increases plasma levels of factor IX and can temporarily correct the coagulation defect in these patients. 

Factor VIII (FVIII) is an essential coagulation factor in the blood which serves as a cofactor in the complex blood-clotting cascade. A deficiency in FVIII is the... 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 121—144. Wilson, pp 23—98.) Hemophilia A is caused by deficiency of factor VIII and hemophilia B by deficiency of factor IX. Both factors are involved in the intrinsic blood coagulation pathway that results in activation of factor X. Alternatively, factor X can be activated by tissue factors through the extrinsic blood coagulation pathway Activated factors X and V produce thromin from prothrombin, which in turn cleaves fibrinogen to produce fi-... 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Flemophilia A and B coagulation defects, which are caused by deficiencies of Factor VIII and Factor IX, respectively, can be bypassed by administration of recombinant Factor Vila. Flowever, the short half-life of recombinant Factor Vila in vivo negates its routine clinical use. An in vivo method for the continnons generation of Factor Vila is reported which depends on tlie implantation of a porous chamber that contains Factor Xa or Xlla and continuously generates Factor Vila bypass activity from the subject s own Factor VII, which enters the chamber by diffusion. Once inside, the Factor VII is cleaved to Factor Vila by the immobilized Factor Xa or Xlla. Tlie newly created Factor Vila diffuses ont of the chamber and back into cuculation, where it can bypass the deficient Factors VIII or DC and enable coagulation to occur. In vitro, tliis method generates sufficient Factor Vila to sub-... 

Gene cloning could potentially provide contaminant-free blood products of high purity. A coagulation factor, Factor VIII, is required by certain haemophiliacs. The risk of hepatitis and acquired immune deficiency syndrome (AIDS) due to the unintentional collection of blood from virus carriers identified this factor as a candidate for production by DNA recombinant techniques. 

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