Deficiency, viii

Sidransky, H. and Vemey E., Chemical pathology of acute amino acid deficiencies. VIII. Influence of amino intake on the morphologic and biochemical changes in young rats force-fed a threonine-devoid diet, /. Nutr., 86, 73, 1965. 

Determination of the potency of Factor VIII is also difficult. This is normally measured by the abiUty of the sample to correct the clotting time of plasma deficient in Factor VIII. A number of methods and practices have evolved for this purpose (231), but these give very different results, particularly when activation of products may also occur (232). International standards have been used, but further standardization of the analytical method and harmonization of working standards is underway (233,234) under the auspices of the ISTH and the EC. 

Hereditary deficiency of Factor V is a rare autosomal recessive disorder. Combined deficiencies of Factors V and VIII have been identified in several families. 

Deficiency of the VIIFC portion of the Factor VIII complex results in classic hemophilia or hemophilia A and is inherited as a sex-linked recessive disorder. Based on the degree of deficiency of the VIIFC molecule three different forms of hemophilia A are recognized. Less than 1% VIIFC activity equals severe hemophilia A. Two to 10% of normal VIIFC activity equals moderately severe hemophilia A. Ten to 25% of normal VIIFC activity equals minimal symptomatic disease. Deficiency of the VIIFvWFAg portion of the Factor VIII complex results in von WiUebrand disease. There are at present five principal types of von WiUebrand disease and numerous subtypes or variants. For the most part, von WiUebrand disease is inherited as an autosomal dominant, and a few subtypes may be inherited as an autosomal recessive trait. 

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

Type VIII Deficiency of liver phosphorylase kinase As for type VI. 

Combined deficiency of factors V and VIII, 227300 ERGIC-53, a mannosebinding lectin... 

The term MPS V is no ionger used. The existence of MPS Viii (suspected giucosamine 6-suifatase deficiency MiM 253230) has not been confirmed. At ieast one case of hyaiuronidase deficiency (MPS iX MiM 601492) has been reported. 

Inherited deficiencies of the clotting system that result in bleeding are found in humans. The most common is deficiency of factor VIII, causing hemophilia A, an X chromosome-hnked disease that has played a major role in the history of the royal families of Europe. Hemophilia B is due to a deficiency of factor IX its clinical Feamres are almost identical to those of hemophilia A, but the conditions can be separated on the basis of specific assays that distinguish between the two factors. 

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... 

The severity of bleeding associated with hemophilia correlates with the degree of factor VIII or factor IX deficiency as measured against the normal plasma standard. Table 64-1 summarizes the age at onset and laboratory and clinical manifestations of hemophilia.3... 

Type 2 vWD deficiency of vWF and factor VIII Qualitative abnormalities of vWF 10%-30% Autosomal dominant... 

A 2B 2M 2N Type 3 vWD Decreased platelet-dependent vWF function owing to lack of larger multime rs Increased platelet-dependent vWF function owing to lack of larger multime rs Defective platelet-dependent vWF functions not associated with multimer defects Defective vWF binding to factor VIII Severe quantitative deficiency of vWF 1 %-5% Autosomal recessive... 

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... 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Proplex T (Factor IX Complex)—used for factor VIII inhibitors, and factor VII or IX deficiency... 

Oxygen and nitrogen electron-deficient intermediates will be discussed as analogs of carbonium ions in Chapter VIII. 

Haemophilia A (classical haemophilia, often simply termed haemophilia) is an X-linked recessive disorder caused by a deficiency of factor VIII. Von Willebrand disease is a related disorder, also caused by a defect in the factor VIII complex, as discussed below. 

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). 

In liver phosphorylase deficiency (glycogenosis type VI, Hers disease Fig. 42-1) and in two genetic forms of phosphorylase kinase deficiency, one of which is X-linked recessive, the other of which is autosomal recessive, hypoglycemia is either absent or mild. Symptoms of brain dysfunction do not usually occur (type VIII, Fig. 42-1) [1],... 

Cryoprecipitate and factor VIII are generally not indicated in acute hemorrhage but may be used once specific deficiencies have been identified. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

System 7, 9, 10. roots-rizosphere (VII) plants (VIII) their biological reactions— metabolism (VIII) soil-soil solution, air (IV) aerosols—atmospheric air (26, 28). In this system, the influence of metal-organic complexes on the plant development and their metabolism is considered. Under deficient or excessive contents of some chemical species, the metabolism may be destroyed (see Figure 2). 

Cycloaddition reactions between alkenes and noncarbohydrate, carbonyl compounds have been described in discussing the reactions of alkenes (see Table I and Scheme 1). The depiction of the excited carbonyl given in Scheme 6 is useful in understanding the regiochem-istry of the cycloaddition process, as it suggests that the electron-deficient oxygen atom in the excited carbonyl will react with the alkene to produce the (more-stable) 1,4-diradical. Table VIII lists cycloaddition reactions in which the excited carbonyl is part of a carbohydrate. 

Answer A. The most likely explanation for mild expression in a heterozygouscarrieris that when X inactivation occurred in the affected individual, the random process happened to inactivate most of the X chromosomes that carried the normal version of the factor VIII gene. Thus, most of the active X chromosomes in this individual would carry the mutation and would not produce factor VIII, leading to a clinically expressed deficiency. 

---