Factor IX Deficiency

I. Review - Factor IX(FIX):

Factor IX is the precursor to Factor IXa, which is a Vitamin K-dependent serine protease that catalyzes the activation of Factor X to Xa
FIX normally circulates in the plasma in an inactive form. Factor VIIIa plays a role in the enzymatic activation of FIX to FIXa.
FIX can also be activated directly by Tissue Factor - Factor VIIa complex in the extrinsic pathway.
FIXa is a serine protease.

II. Hemophilia B (Christmas Disease)

A. Inheritance is x-linked recessive.

B. Incidence is 1 in 30,000 live male births.

C. Mechanism - quantitative deficiency in the synthesis of FIX

D. Clinical features - identical to Hemophilia A

1. Suspect hemophilia in any male who has history of extensive bleeding after trauma or spontaneous bleeding into joints or muscles.

2. Bleeding at time of circumcision

3. Severity of bleeding depends on level of FIX

Severe hemophilia - FIX < 1% - at risk for spontaneous hemorrhages and soft tissue bleeds.
Moderate hemophilia - FIX 1-4%
Mild hemophilia - FIX 5-50% - little risk for spontaneous bleeds but may bleed excessively following surgery or trauma.

E. Lab abnormalities

1. Prolongation of aPTT (variable with degree of hemophilia)

2. Decreased FIX acitvity

3. Normal bleeding time and thrombin time.

F. Management

1. Avoid aspirin

2. Mild hemophilia - Antifibrinolytics such as aminocaproic acid may be helpful. For major surgery, give FIX concentrates perioperatively. For surgery, the FIX activity should be maintained between 30-60%. Higher levels may lead to thrombosis (see below).

3. Moderate and Severe hemophilia - give FIX concentrate at the earliest sign of bleeding.

4. Available forms of FIX

FIX concentrates
Prothrombin complex - contains the inactive Vitamin K-dependent clotting factors
Activated prothrombin complex - contains the active Vitamin K-dependent clotting factors.
Fresh frozen plasma - contains FIX. Limited by the fact that unless exchange transfusion is done, sufficient FFP cannot be given to patients with severe hemophilia to raise FIX levels sufficiently in order to prevent or control bleeding episodes.

5. Considerations of FIX treatment

Prolonged infusion of FIX concentrates has been associated with thromboembolic events, i.e. disseminated intravascular coagulation, pulmonary embolus, and deep venous thrombosis - especially in those patients with liver disease.
Therefore, if prolonged FIX infusion is necessary, often a small amount of heparin will be added to the FIX solution.