Haemophilia

General paediatrics, Haem/Oncology

The clinical severity of a patient’s hemophilia is gauged by the baseline clotting factor level, a value that remains fairly constant throughout that person’s life, and is pretty consistent through a family. Around 5% of normal is moderate.

Intramuscular injections should be avoided if at all possible. If they must be given, factor replacement therapy should precede the injection. Parenteral agents should be given intravenously or subcutaneously. Immunizations are administered subcutaneously.

Aspirin is contraindicated due to antiplatelet effect. Avoid NSAIDs if possible, and contraindicated if actively bleeding or being treated for a recent bleeding problem.

Indications for Factor Replacement Therapy

  1. Suspected bleeding into a joint or muscle.
  2. Any significant injury to the head, neck, mouth or eyes or evidence of bleeding in those areas.
  3. Any new or unusual headache, particularly one following trauma.
  4. Severe pain or swelling at any site.
  5. All open wounds requiring surgical closure, wound adhesive, or steri-strips.
  6. History of an accident or trauma that might result in internal bleeding.
  7. Necessity of a surgical or invasive procedure.
  8. Heavy or persistent bleeding from any site.
  9. Gastrointestinal bleeding.
  10. Acute fractures, dislocations and sprains.

Treatment

Hemophilia A

The treatment of choice for individuals with factor VIII deficiency is recombinant factor VIII. There are different brands, with different combinations of additives which may or may not be antigenic. Cryoprecipate and fresh frozen plasma are used only if factor cannot be obtained.

  • When bleeding is severe, or for a head injury, the appropriate dose of factor VIII is 50 units/kg. This should result in a factor VIII level of 80-100%. Half life is 8-10 hrs so repeat if necessary.
  • Mild Hemophilia A (factor VIII greater than 5%) with Non-Life/ Limb Threatening Bleeding may respond to desmopressin (some don’t) – 0.3mcg/kg IV over 30 minutes, else as nasal spray (Stimate, 1 spray in one nostril for individuals <50 kg and 1 spray in each nostril for individuals >50 kg). Otherwise, treatment dose is 15-25u/kg.

Hemophilia B

For individuals with Christmas disease (factor IX deficiency), recombinant factor IX is the treatment of choice. Fresh frozen plasma is only used if factor is unavailable.

  • When bleeding is severe, or head injury, the appropriate dose of factor IX is 100-120 units/kg. This should result in a factor IX level of 80-100%, but in Hemophilia B the response is variable so check the level and adjust as necessary.
  • Mild – 25-35u/kg, check level

Ideally let patients/parents reconstitute and administer their own factor. Families should have an emergency dose of factor concentrate or DDAVP in their home and to take it with them when they travel, esp if they do not live close to a hospital. Factor replacement should be offered within 1 hour of the patient’s arrival: it should be readily available, the patient should not be left waiting, and treatment should not be deferred pending x-rays or other results. The most experienced IV therapist or phlebotomist available should perform venipuncture – misses and tourniquets may cause painful hematomas which then limit further IV access – use the smallest needle possible unless volume replacement is needed..

Factor replacement must be administered intravenously by IV push over 1-2 minutes. Round the dose up to the closest full vial ie don’t throw away any left overs (excess factor does not create a hypercoaguable state but will prolong the therapeutic half-life of the product administered).

For individuals with inhibitors (antibodies to factor VIII or IX), treatment decisions may be more complicated. The care of inhibitor patients should be urgently discussed with the patient’s hematologist. If an individual with an inhibitor presents in a life- or limb-threatening scenario, the safest immediate action is to prescribe recombinant factor VIIa (rFVIIa, Novoseven) at a dose of 90 mcg/kg or activated prothrombin complex concentrates (FEIBA, Autoplex) at 75-100 units/kg (contraindicated in factor IX patients with a history of inhibitors and anaphylaxis). Hopefully the patient/family can provide information on response to second line therapeutic agents.

[Medical and Scientific Advisory Council (MASAC) of the US National Hemophilia Foundation 2003]