Hemophilias

A young African-American male patient is brought to you because of a hemarthrosis sustained after he twisted his knee while running. His PT is normal, but his APTT is 51 s (normal 20-32 s). Mixing equal volumes of the patient s plasma and normal plasma shortens the APTT to 25 s. Specific factor assays show a normal factor IX activity, but a factor VIII activity of 25% of that in pooled normal plasma. Why was his PT normal What else, prior to the factor IX and VIII assay results, might have been responsible for the prolonged APTT  

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DNA sequence data have been used to investigate inherited diseases such as hemophilia and muscular dystrophy, and also in cancer research. 

Hemoglobin S Hemoglobins Hemolysis Hemoperfusion Hemophan Hemophilia... 

Hemophilia A Hemophilus influenzae Hemorrhage Hemorrhoids Hemosiderin Hemo stats Hemp... 

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

Factor IX complex treatment of hemophilia B and other coagulation 57 5 X 10-"... 

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. 

Congenital deficiency of Factor IX results in hemophilia B, also known as Christmas disease, and is inherited in a sex-linked recessive manner. Instmctive is the fact that some female carriers are symptomatic. Combined deficiencies of Factors VIIFC and IX have been described. 

Table 4 contains products available for Factor VII, Factor VIIFC (hemophilia A), Factor IX, and von Willebrand protein deficiency. Table 5 fists miscellaneous hemostatics and thein proposed mechanisms of action. 

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). 

Kut stiU6tift m. styptic pencil. -iStrom m. blood stream, -sucht, /. hemophilia. um lauf, m. circulation of the blood. 

In the body, proteins are built up by a series of reactions that in general produce a specific sequence of amino adds. Even tiny errors in this sequence may have serious effects. Among the genetic diseases known to be caused by improper sequencing are hemophilia, sickle cell anemia, and albinism. Sickle cell anemia is caused by the substitution of one valine unit for a glutamic add unit in a chain containing 146 monomers. 

Manno CS, Pierce GF, Arrada VR et al (2006) Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 12(3) 342-347... 

Diabetes insipidus, hemophilia A, von Willebrand s disease, nodurnal enuresis... 

Ehrhardt A, Xu H, Dillow AM, Bellinger DA, Nichols TC, Kay MA (2003) A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102 2403-2411... 

In past years, treatment for patients with hemophilia A has consisted of administration of cryoprecipitates (enriched in factor VIII) prepared from individual donors or lyophilized factor VIII concentrates prepared from plasma pools of up to 5000 donors. It is now possible to prepare factor Vlll by recombinant DNA technology. Such preparations are free of contaminating viruses (eg, hepatitis A, B, G, or HlV-1) found in human plasma but are at present expensive their use may increase if cost of production decreases. 

Hemophilia A Is Due to a Genetically Determined Deficiency of Factor Vlll... 

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. 

Genetic disorders of coagulation factors occur, and the two most common involve factors VIII (hemophilia A) and IX (hemophilia B). 

Nineteen women underwent amniocentesis for the determination of fetal sex. Several different X-llnked abnormalities constituted the Indications for this procedure, and these Included hemophilia A, hemophilia B, Duchenne muscular dystrophy, optic albinism, X-llnked mental retardation, the Lesch-Nyhan syndrome (due to dlflclency of hypoxanthlne-guanlne phosphorlbosyltransferase, and Fabry s disease (due to deficiency of an a-galact-osldase). Fourteen of the fetuses were male. Including one which turned out to be a set of twins, and most of the male pregnancies were terminated. The sex determination being carried out for Fabry s disease Is of particular Interest, since In this case It was desired to find out whether the fetus was a female. 

Hemophilia or other hemorrhagic tendencies Severe liver disease with elevated baseline PT Severe thrombocytopenia (platelet count less than 20,000) Malignant hypertension... 

List the complications from hemophilia bleeding episodes. 

Hallmark of hemophilia recurrent inadequately managed hemarthrosis leads to chronic deformity and pain. 

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