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Hemophilia

Hemophilia A and B, which are clinically indistinguishable, are inherited as X-linked, recessive diseases, occurring in approximately one in every 5,000 male births. Hemophilia C, or more properly factor XI deficiency, will be considered separately, since the clinical syndromes are quite different and vary considerably. Although many textbooks suggest a variety of ethnic and racial influences on incidence and prevalence of hemophilia A and B, more recent epidemiologic data from the Centers for Disease Control and Prevention suggest strongly that the incidence does not vary according to ethnicity.

While the clinical conditions of hemophilia A and B remain indistinguishable, the proteins in which defects produce the disorders of Classic hemophilia A and hemophilia B or Christmas disease (Factor VIII and Factor IX, respectively) were separated from each other.

Patients with severe hemophilia bleed spontaneously, most often into joint cavities (hemarthroses); those with moderate hemophilia bleed less often on a spontaneous basis and more commonly associated with minor trauma; those with mild hemophilia often are asymptomatic until provoked with surgical stress or severe trauma.

III. Prenatal diagnosis of hemophilia

Knowledge of the molecular aspects of the factor VIII and factor IX genes has allowed for the development of accurate techniques for the diagnosis of hemophilia in utero in female carriers. Currently, chorion villous sampling (CVS) in gestational weeks 10-11 provides the genetic material needed to define the mutation responsible for hemophilia in the family.

Phenotypic assessment for carrier status Or for prenatal detection (eg, when-a fetal blood sample is available) is less accurate. Conclusive Identification of a carrier can only be accomplished when the functional activity of either factor VIII or factor IX is very low. Plotting the ratio of factor VIII activity to the level of the von Willebrand factor increases.

IV. Treatment of hemophilia-replacement therapy

Patients with severe hemophilia can experience between 30 to 50 joint bleeds Yearly, requiring an average of 50,000 units per year for treatment of these acute hemarthroses. When treatment is administered at the first evidence of a bleed is termed "on demand" therapy. Administration of factor concentrates in anticipation of and for the prevention of bleeding episodes is called prophylaxis. Primary prophylaxis is defined as prevention treatment initiated.

While several, small acute and chronic studies from Scandinavia and Europe have supported the utility of primary prophylaxis for the prevention of joint disease when initiated before the age of 2 or at the time of the first bleeding episode, the results of a larger, randomized controlled trial.

This approach is quite expensive, however, and third party reimbursement over the long-term will require a positive cost-effectiveness analysis, which is being performed in the RCT. Difficulty with venous access in small children increases further the cost of this treatment and is associated with the complications of indwelling catheters (eg, infection and thrombosis of catheters).

V. Choice of clotting factor concentration

Since the mid-1970s, the conventional treatment for patients with either severe hemophilia A or B relied on the use of lyophilized concentrates of clotting factors derived from plasma from as many as 600,000 individual donors. The purification : methodology developed created unwittingly an unprecedented exposure of a group of patients to the distillate of all potentially transmissible agents contained in the blood supply and produced the worst iatrogenic disaster in the history of medical science blood transfusion-transmitted HIV disease.

VII. Hemophilia C (Factor XI Deficiency)

Factor XI deficiency is an autosomal recessive hereditary bleeding disorder that occurs in approximately 1/1,000,000 live births. It has been reported predominantly in Ashkenazi Jews of European descent and is characterized typically by a mild bleeding disorder, which usually becomes evident after trauma or surgery. Only rarely is hemophilia C.

Factor XI genotypes influence the severity and frequency of bleeding complications, as follows. Type II homozygotes and Type 11_/11] heterozygotes manifest the highest incidence of excessive bleeding. In these patients factor XI is replaced with fresh frozen plasma or cryosupernatant (1S-20ml/kg loading dose followed by 5-10mL/kg/d x 7-10 days).