Bleeding disorders hemophilia

Factor IX (Christmas factor) is next in the intrinsic mechanism cascade. It can be activated either by XIa or by Vila of the tissue factor pathway. The absence of a functional factor IX leads to the inherited X-linked bleeding disorder hemophilia B which affects 1 in 30,000 males. The condition can be mild or very serious551552 and may be caused by a variety of mutations or by incorrect splicing of the messenger RNA for the 416-residue factor IX. The level of factor IX in blood increases with age, almost doubling by old age.552a... 

Birth defects, neural tube defects, 514-516 Bispbosphenate, 776 Bleeding disorders hemophilia, 537 scurvy, 618... 

Bleeding disorders—hemophilia Aspirin Increased risk of hemorrhage... 

United Kingdom Hemophilia Centre Doctors Organisation (UKHCDO). Guidelines on the selection and use of therapeutic products to treat hemophilia and other hereditary bleeding disorders. Hemophilia 2003 9 1-23. 

Recombinant DNA techniques have enabled the cloning of Factor VIII, which is missing from most patients with the inherited bleeding disorder hemophilia. Factor VIII is essential for proper blood clotting, and untreated hemophilia patients suffer from severe uncontrolled bleeding. Recombinant Factor VIII is used to restore clotting activity to the blood of hemophiliacs. 

The term molecular medicine is defined as understanding disease at the molecular level. For example, the deficiency of factor VIII causes a bleeding disorder, Hemophilia A [3]. Given the accomplishments made in the area of human genome and the emergence of proteomics, functional proteins that have important therapeutic value have been developed, and more will be identified in the future. 

Von Willebrand disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor. The disease prevalence is estimated at 30 to 100 cases per million. In contrast to hemophilia, vWD is inherited as an autosomal dominant disorder (although autosomal recessive cases exist), ensuing equal frequency in male and females.16... 

Hemophilia B, another X-linked recessive bleeding disorder, is caused by a deficiency of dotting factor IX. 

The hemophilias are a group of related, usually inherited, bleeding disorders. Inherited bleeding disorders include abnormalities of coagulation factors as well as platelet function. When the term hemo-... 

There have been several reports of seizures in association with hyponatremia after intravenous administration of desmopressin to cover surgery in young children with congenital bleeding disorders such as mild hemophilia A or von Willebrand s disease (58-60). Hyponatremia and convulsions have occurred in children without congenital bleeding disorders who received desmopressin for urine concentration tests or to treat nocturnal enuresis (54,61,62). 

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 ... 

Hemophilias (Bleeding Disorders Not Related to Vitamin K Status)... 

Patients with bleeding disorders are at risk of developing antibodies against the protein that is absent, present in reduced amounts, or present in an inactive form in their blood. Such coagulation inhibitors make treatment very difficult. Inhibitors of factor VIII are the most common and develop in 5-20% of patients with hemophiha A. Inhibitors of factor IX develop in 1-4% of patients with hemophilia B (3,4). Patients with factor VIII inhibitors present clinically either as high responders who show a strong anamnestic response and a sharp rise in inhibitor concentrations after exposure to factor VIII, or low responders, who show little or no anamnestic response (5). 

A (congenital or acquired) and type 1 von Willebrand disease, in which the VWF protein structure is normal but the plasma concentration is reduced (1). By contrast with conventional coagulation factor concentrates, desmopressin is cheap and is free from the risk of transmission of viral infections, which have proved such a problem in the past. It is also very useful in the treatment of carriers of hemophilia A, many of whom have significant reductions in the baseline concentration of factor VIII. By contrast, desmopressin has no effect on the concentration of factor IX, and is thus of no value in hemophilia B (Christmas disease). It is also of little value in type 2 (abnormal VWF structure) von Willebrand s disease, which accounts for about 15-20% of all cases. The administration of desmopressin to patients with type 2B von Willebrand s disease can be hazardous, as it is likely to cause thrombocytopenia (2). The use of desmopressin in bleeding disorders has been reviewed (3). Tachyphylaxis develops if desmopressin is used for prolonged periods to control bleeding disorders, because desmopressin causes release of stored factor VIII and von Willebrand factor, after which it takes time for them to accumulate again. 

In another clinical study, patients suffering from hemophilia B, which is a bleeding disorder caused by a deficiency of coagulation factor IX, were treated with AAV vectors expressing human factor IX (13 9). These patients participated in a Phase I trial and received intramuscular injections of AAV vectors. Although only very low levels of secreted factor IX could be detected in the plasma of one patient, the treated patients showed some clinical benefits and a reduced intake of factor IX infusions. Moreover, no vector-related toxicity and germ line transmission was observed. 

Wang L, Takabe K, Bidlingmaier SM, 111 CR, Verma IM. Sustained correction of bleeding disorder in hemophilia B mice by gene therapy. Proc Natl Acad Sci USA 1999 96 3906-3910. 

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