Blood factor VIII deficiency

Cryoprecipitate may also be used for patients with factor VIII deficiency and von Willebrand disease if desmopressin is not indicated and a pathogen-inactivated, recombinant, or plasma-derived product is not available. The concentration of factor VIII and von Willebrand factor in cryoprecipitate is not as great as that found in the concentrated plasma fractions. Moreover, cryoprecipitate is not treated in any manner to decrease the risk of viral exposure. For infusion, the frozen cryoprecipitate unit is thawed and dissolved in a small volume of sterile citrate-saline solution and pooled with other units. Rh-negative women with potential for childbearing should receive only Rh-negative cryoprecipitate because of possible contamination of the product with Rh-positive blood cells. 

Bi, L., Sarkar, R., Naas, T., Lawler, A. M., Pain, J., Shumaker, S. L., Bedian, V. and Kazazian, H. H., Jr. (1996). Further characterization of factor VIII-deficient mice created by gene targeting RNA and protein studies. Blood 88, 3446-3450. 

Blood factor VIII (FVIII) is a glycoprotein with 2351 amino acids and 330 kDa. Its deficiency causes hemophilia A. The first products based on recombinant factor VIII to reach the market were Recombinate and Kogenate, expressed in CHO and BHK cells, respectively. Over the last decade, other rFVIII products were approved, with modifications to the molecule (e.g. deletion of the B-domain), in the formulation or in the production processes. 

Giles AR,Tinlin S, Hoogendoorn H, Fournel MA, Ng P, Pancham N. In vivo characterization of recombinant factor VIII in a canine model of hemophilia a (factor VIII deficiency). Blood 1988 72 335-9. 

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). 

Antihemophilic factor, a blood derivative, is indicated for the treatment of hemophiha A (factor VIII deficiency). Anti-hemophihc factor replaces deficient clotting factors that convert prothrombin to thrombin (see Tables 17 and 18). 

Neerman-Arbez, M., K. M. Johnson, M. A. Morris, J. H. MeVey, F. Peyvandi, W. C. Nichols, D. Ginsburg, C. Rossier, S. E. Antonarakis, and E. G. Tuddenham, Molecular analysis of the ERGlC-53 gene in 35 families with combined factor V-factor VIII deficiency. Blood, 1999, 93, 2253-2260. 

Rubin, H., Fernbach, T., and Ritz, N. D., 1970, Corrective effect of sialic acid on the clotting of factor VIII deficient blood, Thromb. Diath. Haemorrh. 24 152. 

Individuals who display a deficiency of factor IX develop haemophilia B, also known as Christmas disease. Although its clinical consequences are very similar to that of a deficiency of factor VIII, its general incidence in the population is far lower. Persons suffering from haemophilia B are treated by i.v. administration of a concentrate of factor IX. This was traditionally obtained by fractionation of human blood. Recombinant factor IX is now also produced in genetically engineered CHO cells (Table 12.2 and Box 12.1). 

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... 

Factor VIII promotes clotting it is deficient in hemophiliacs treatment with factor VIII produced by recombinant DNA technology eliminates infection risks associated with blood transfusions. 

Giles AR, Tinlin S, Greenwood R (1982) A canine model of hemophilic (factor VIII C deficiency) bleeding. Blood 60 727-730... 

Genetically, determined clotting diseases include classical haemophilia, which is due to lack of factor VIII, and there is another form of haemophilia due to deficiency of factor IX (Christmas factor). These are treated by giving fresh donor blood or plasma, preparations of factor VIII or factor IX, or increasingly as one of the recombinant versions which are becoming available. 

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-... 

This ignorance led to alarm as the first cases appeared in haemophiliacs, who had received the blood protein factor VIII. This was not only a serious health concern but also a major commercial problem, since worldwide sales of blood products was estimated to be around two billion US dollars. For haemophiliacs, the situation was dire. Because of the large quantity of blood plasma that had to be processed in order to obtain factor VIII, and the large number of injections they needed each year, it was estimated that each patient could be exposed to the blood of up to three million donors. At this time, the manufacturers of factor VIII did not use heat-treatment procedures, as they did from 1987, but nonetheless, the causative agent appeared to be pretty rugged. The appearance of the disease in haemophiliacs rendered the name GRID inappropriate for the condition, and this was now replaced by the term Acquired Immune Deficiency Syndrome or AIDS. 

Factor IX complex, a blood derivative with hemostatic properties, is used in factor IX deficiency (hemophilia B or Christmas disease) in patients with factor VIII inhibition, in factor VII deficiency, and in overdosage with anticoagulant (see also Tables 17 and 18 and Figure 92). 

Thrombin is activated by proteolytic cleavage of its precursor protein, prothrombin. The sequence of proteolytic cleavages leading to thrombin activation requires Factor VIII, the blood-clotting protein deficient in Sloe Klotter. 

Haemophilia is due to a deficiency or defect of Factor VIII and is treated by administration of blood plasma or plasma concentrate containing the factor. Factor VIII can now be obtained from genetically engineered cell cultures, which avoids the risk of contamination with viruses, notably HIV (the AIDS virus). 

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