Factor IX Activity

Factor IX is a 72 kilodalton vitamin K-dependent glycoprotein proenzyme that is produced by the liver.⁶ Factor IX's plasma concentration is 3-5 mg/mL and half-life is about 24 hours.⁶ Factor IX deficiency should be suspected when a patient with excessive bleeding has a normal protime (PT) and an extended activated partial thromboplastin time (aPTT).

Hemophilia B, or Christmas disease, occurs as the result of congenital deficiency of factor IX.^6,7 Clinical features of hemophilia B are the same as for hemophilia A, which is caused by factor VIII deficiency (see Factor VIII Activity [086264]). Hemophilia B is less common than hemophilia A, occurring in approximately one of every 30,000 live male births.⁷ The prevalence is significantly higher in Amish and East Indian populations.⁸ This condition is transmitted as an X chromosome-linked hereditary disorder.⁷ The majority of cases occur in men whose mothers are carriers of the genetic defect. A subtype of hemophilia B, hemophilia B Leiden, is characterized by altered developmental expression of factor IX such that plasma factor IX levels may be <1% of normal during childhood, but after puberty may gradually rise to a maximum of 70% of normal.¹² Hemophilia B can also occur as the result of spontaneous mutations of the factor IX gene locus.⁷ Female carriers of hemophilia B may rarely present with excessive bleeding.⁷ Hemophilia symptoms can also occur in female carriers that have a high degree of lyonization of the factor X alleles.⁷ Females with Turner syndrome, karyotype XO, can also be symptomatic.⁷

The severity of hemophilia B can be defined by the level of factor IX activity.^7,8 Severe hemophilia is associated with a factor IX level of <1%. Moderate hemophilia B occurs with factor IX levels of 1% to 5% and mild hemophilia has factor IX levels >5%.

Patients with hemophilia B can present with any of a number of bleeding manifestations.^6,7 Often, infants with severe hemophilia are first diagnosed during the neonatal period because of excessive bleeding after circumcision or due to cord necrosis.⁷ Hemophilic infants also frequently suffer from intracranial hemorrhage or scalp hematomas. Spontaneous hemarthroses, a common symptom of hemophilias, typically do not occur until the child starts walking.^7,8 Hematomas can often be observed at the sites of intramuscular injections for vaccination or medication. The most common sites of spontaneous bleeding in patients with severe hemophilia are involve the joints and muscles. Recurrent bleeding leads to chronic muscle injury and degeneration of the joint tissue.^6,7 Gastrointestinal bleeding can occur in approximately 10% of hemophiliacs.⁷ Males with mild to moderate hemophilia and female carriers may have an increased bleeding tendency, especially following surgery or trauma.⁸

Acquired factor IX deficiency can occur as the result of oral anticoagulant therapy or with vitamin K deficiency.^6,8 Individuals with advance liver disease can have a generalized decrease in coagulation factors, including factor IX.

Elevation of factor IX, if persistent, has been associated with approximately a twofold increased risk for venous thrombosis.⁹ The basis for this increased risk is not well understood and the clinical cutoff for risk assessment has yet to be established.⁹

Hemophilia B patients receiving replacement products can develop inhibitors to factor IX in approximately 3% of cases, due to the production of alloantibodies.^6,10 Acquired hemophilia caused by the development of autoantibodies to factor IX can also occur.¹¹ This rare condition can occurs most often in individuals with autoimmune disorders. These patients have bleeding symptoms similar to those seen in congenital hemophilia B.