Factor IX Concentrate

Factor IX concentrate replaces coagulation factor IX in haemophilia B. Products are plasma-derived or recombinant (conventional and extended half-life), and are given intravenously for bleeds, surgery and prophylaxis.

Classification. Coagulation factor replacement.

Mechanism. Supplies factor IX, which when activated forms the tenase complex with factor VIIIa and activates factor X, restoring thrombin generation.

Pharmacokinetics. One IU/kg raises factor IX by about 1 IU/dL with plasma-derived products and about 0.7 to 0.9 IU/dL with conventional recombinant products (lower in children). Half-life is 18 to 24 hours for conventional products and 80 to 100 hours for extended half-life products.

Dose formula. Units required = weight in kg × desired rise in IU/dL × 1.0 for plasma-derived products; × 1.2 to 1.4 for conventional recombinant products, depending on age and product. Extended half-life products have product-specific factors.

Treatment of bleeding in haemophilia B.

• Minor bleed (early joint or muscle, oral): raise to 20 to 40 IU/dL (20 to 40 IU/kg), repeat every 24 hours for 1 to 3 days.
• Moderate bleed: raise to 30 to 60 IU/dL, repeat every 24 hours for 3 to 4 days.
• Major or life-threatening bleed: raise to 60 to 100 IU/dL (60 to 80 IU/kg), then half the loading dose every 12 to 24 hours for 7 to 14 days.
• Maximum: avoid levels over 100 IU/dL for long periods because of thrombosis risk, especially with prothrombin complex concentrates.

Surgery. Major: raise to 60 to 80 IU/dL before surgery, then keep trough at 30 to 50 IU/dL for 1 to 2 weeks. Minor: raise to 50 IU/dL, then trough 20 to 30 IU/dL for 2 to 5 days.

Prophylaxis. Severe haemophilia B: conventional products 20 to 40 IU/kg twice weekly; extended half-life products 40 to 100 IU/kg every 7 to 14 days, product-specific.

Alternative where pure factor IX is unavailable. Prothrombin complex concentrate (factors II, VII, IX and X) can be used; thrombotic risk rises with repeated high doses, so keep to the lowest effective dose.

Adjustments. Kidney and liver: none. Children: need 20 to 30% more because of lower recovery. Pregnancy: carriers need cover at delivery (target 50 IU/dL or more).

Contraindications. Known anaphylaxis to the product; disseminated intravascular coagulation or fibrinolysis (for prothrombin complex concentrates).

Adverse effects. Allergic reactions, which can be anaphylaxis, headache, fever, thrombosis at high levels. Inhibitors occur in about 3% of patients, often with allergic reactions in the first exposures; nephrotic syndrome can follow immune tolerance induction.

Interactions. None important. Tranexamic acid adds antifibrinolytic effect but is avoided with prothrombin complex concentrates.

Pregnancy and breastfeeding. Used when needed.

Regional points. Supply is limited in East Africa; plasma and cryoprecipitate do not reliably raise factor IX, so concentrate is preferred when available.

Common errors. Applying the factor VIII half-life to factor IX schedules; omitting the recovery factor; repeated doses of prothrombin complex concentrate without monitoring.

Administration. Reconstitute as labelled and give by slow intravenous injection or infusion, at no more than the labelled rate. For patients with severe deletion mutations, give the first doses under observation with resuscitation equipment ready.

Baseline. Factor IX level, inhibitor screen, hepatitis B, hepatitis C and HIV status.

Monitoring. Factor IX peak and trough in surgery or major bleeding. Inhibitor screening with poor response or allergic reaction. Joint and bleeding diary.

Referral and escalation. Any allergic reaction to factor IX needs immediate cessation, adrenaline 0.5 mg intramuscularly (adults) if severe, and inhibitor testing. Refer to a haemophilia centre.