Factor VIII deficiency

Most patients with type 1 vWD (functionally normal vWF) and a minor bleeding episode can be treated successfully with desmopressin, which induces secretion of autologous factor VIII and vWF into plasma. The recommended dose is the same as that used to treat mild factor VIII deficiency (0.3 mcg/kg intravenously in 50 mL of normal saline infused over 15 to 30 minutes). This therapy generally is ineffective in type 2A patients who secrete qualitatively abnormal vWF and is controversial in type 2B patients because it may increase the risk of postinfusion thrombocytopenia. Type 3 vWD patients who lack releasable stores of vWF do not respond to DDAVP therapy.18... 

Therapy is determined by the level of factor VIII deficiency. Severely affected patients have concentrations less than 1 %, in moderate disease this is present between 1 and 5 % whereas plasma levels between 5 and 30 % may be associated with bleeding only after trauma such as dental extraction. Additionally, the choice of replacement is modified by the site of bleeding and the presence or absence of inhibitors that interfere with the function of the factor. Cryoprecipitate or lyophilised concentrate is becom-... 

Cryoprecipitate should be used to treat bleeding in the setting of factor VIII deficiency and von Willebrand disease only in an emergency in which pathogen-inactivated products are not available. 

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. 

Lipshutz, G. S., Sarkar, R., Flebbe-Rehwaldt, L., Kazazian, H. and Gaensler, K. M. (1999). Short-term correction of factor VIII deficiency in a murine model of hemophilia A after delivery of adenovirus murine factor VIII in utero. Proc. Natl. Acad. Sci. USA 96, 13324-13329. 

There are two types of hemophilias that have been identified, hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). The incidence of hemophilia A is I in every 5000 live male births and for hemophilia B the incidence is I in every 30,000 live male births. Both types of hemophilia are... 

Antonarakis SE, Kazazian HH, Tuddenham EG. Molecular etiology of factor VIII deficiency in hemophilia A. Hum Mutat 1995 5(l) l-22. 

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). 

Another possibility is that some other clotting factor is increased or activated in such a way that the assay system responds fortuitously to it in a way indistinguishable from the usual response to factor VIII, e.g., factors XI and XII factor XII is known to rise on exercise (II). That this might occur over a limited range of the dose-response curve in the thromboplastin generation test system was shown by experiments in which the addition of activation product (Wl) simulated an increased factor VIII concentration (author s unpublished observations, 1960 FI), although statistical invalidity would probably be detectable over a series of experiments if this were the explanation. This also was looked for, but was not found (14). It is interesting that, in a patient with severe factor VIII deficiency and partial factor XI deficiency (SI), adrenaline infusion was followed by a marked rise in factor XI concentration and the appearance of a trace of factor VIII (K. Schulz, personal communication, 1964). Furthermore, the confusion that arose some years ago over factor IX assay now seems to have been due to activation of the contact factors (P4), hence... 

The dose of desmopressin for von WiUebrand disease is identical to that used in the treatment of mild factor VIII deficiency, 0.3 mcg/kg diluted in 30 to 50 mL of normal saline and given intravenously over 15 to 30 minutes. In general, patients with von WiUebrand disease have a better response to desmopressin than those with hemophilia, with an average three- to fivefold rise in von WiUebrand factor and factor VIII levels. These levels remain elevated for about 6 to 8 hours. The response to desmopressin in a given patient is usuaUy consistent, and a trial of desmopressin should establish if the medication is likely to be effective for the individual. Desmopressin is preferable to the use of plasma-derived products for patients who have an adequate response because desmopressin does not carry a risk of viral transmission. An added benefit is that desmopressin is substantiaUy less costly than the plasma-derived products. (For a discussion of the side effects of desmopressin, see the section on the treatment of hemophUia A.)... 

Clinically, disorders of Factor VIII are the most common inherited abnormalities of hemostasis. Classical hemophilia A, Factor VIII deficiency, occurs in approximately 1 out of 20,000 live births in the United States. 

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. 

Salmon et al., 1970), pseudocholinesterase deficiency (Hodgkin et al., 1965), myophosphorylase deficiency (Robbins, 1960), acatalasia (Nishi-mura et al., 1961 Takahara et al., 1962), a variant of factor VIII deficiency (hemophilia) (Feinstein et al., 1969), and several others (Boyer et al., 1973). Because of the absence of any identifiable protein in these conditions, it has been cautioned that enzyme or nonenzyme replacement be carefully weighed, since the patient may treat such replacement as foreign protein (Boyer et al., 1973). 

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. 

---