Factor VIII Concentrate

Factor VIII concentrate replaces coagulation factor VIII in haemophilia A. Products are plasma-derived or recombinant, with conventional and extended half-life forms, and are given intravenously for bleeds, surgery and prophylaxis.

Classification. Coagulation factor replacement.

Mechanism. Supplies factor VIII, a cofactor for activated factor IX in the tenase complex, restoring thrombin generation.

Pharmacokinetics. One IU/kg raises plasma factor VIII by about 2 IU/dL (2%). Half-life is 8 to 12 hours for conventional products, 12 to 19 hours for extended half-life products, and shorter in children. Recovery is lower in young children and with inhibitors.

Dose formula. Units required = weight in kg × desired rise in IU/dL × 0.5.

Treatment of bleeding in haemophilia A (without inhibitors).

• Early haemarthrosis, minor muscle or oral bleed: raise factor VIII to 30 to 40 IU/dL (15 to 20 IU/kg), repeated every 12 to 24 hours for 1 to 3 days.
• Moderate bleed (larger haematoma, haematuria, deeper muscle): raise to 40 to 60 IU/dL (20 to 30 IU/kg), every 12 to 24 hours for 3 to 4 days until resolved.
• Major or life-threatening bleed (intracranial, gastrointestinal, retroperitoneal, iliopsoas, neck): raise to 80 to 100 IU/dL (40 to 50 IU/kg) at once, then 20 to 25 IU/kg every 8 to 12 hours for 7 to 14 days.
• Maximum: avoid sustained levels over 150 IU/dL because of thrombosis risk.

Surgery. Major: raise to 80 to 100 IU/dL before surgery, then keep trough at 50 IU/dL or more for the first 3 to 5 days and 30 IU/dL or more through healing (usually 10 to 14 days). Continuous infusion (after a bolus, 3 to 4 IU/kg/hour) is an alternative. Minor: 40 to 60 IU/dL, then 30 IU/dL for 3 to 5 days.

Prophylaxis. Severe haemophilia A (factor VIII under 1 IU/dL): 20 to 40 IU/kg three times weekly or on alternate days; extended half-life products every 3 to 5 days at 30 to 50 IU/kg. Where supply is limited, low-dose prophylaxis of 10 to 15 IU/kg two to three times weekly reduces bleeding but gives less joint protection.

Inhibitors. Low titre (under 5 Bethesda units): higher doses may overcome inhibitors. High titre: use bypassing agents (activated prothrombin complex concentrate 50 to 100 units/kg every 8 to 12 hours, maximum 200 units/kg daily; recombinant activated factor VII 90 µg/kg every 2 to 3 hours) and consider emicizumab and immune tolerance induction.

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

Contraindications. Known anaphylaxis to the product, including to hamster or mouse protein for some recombinant products.

Adverse effects. Inhibitor development (up to about 30% in previously untreated severe haemophilia A, mostly within the first 20 exposure days), allergic reactions, headache, fever, infusion-site reactions, thrombosis at high levels. Plasma-derived products are virally inactivated.

Interactions. None important. Desmopressin can be used in mild haemophilia A. Emicizumab prophylaxis alters laboratory assays.

Pregnancy and breastfeeding. Used when needed.

Regional points. Supply in East Africa is limited and often by donation, so on-demand dosing is common. If concentrate is unavailable, cryoprecipitate or fresh frozen plasma are fallbacks, with infection and volume risks. Treat bleeds early, ideally within 2 hours of onset.

Common errors. Delaying treatment; under-dosing; repeating at the wrong interval; failing to test for inhibitors after poor response.

Administration. Reconstitute as labelled and give by slow intravenous injection, no faster than the labelled rate (commonly up to 10 mL/min). Home treatment after training. Store at 2 to 8°C unless the label permits room temperature storage.

Baseline. Factor VIII level, inhibitor screen, hepatitis B, hepatitis C and HIV status, joint assessment.

Monitoring. Factor VIII peak and trough in surgery or major bleeding; inhibitor testing (Bethesda assay) after 20 exposure days in young patients, before surgery and with poor response; joint and bleeding diary.

Referral and escalation. Any head, neck, abdominal or eye bleed needs immediate infusion and hospital referral. Refer inhibitors and surgery to a haemophilia centre.