Clinical Practice Guidelines

Haemophilia


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    This guideline has been adapted for statewide use with the support of the Victorian Paediatric Clinical Network

  • See also: 

    Von Willebrand disease

    Background

    • Haemophilia is an X-linked bleeding disorder affecting ~ 1 in 7000 males.
    • Haemophilia A is Factor VIII (8) deficiency.
    • Haemophilia B is Factor IX (9) deficiency.

    Clinical characteristics of Haemophilia A and B

    Severity  Concentration of
    Clotting Factor (%) 
    Typical Bleeding Picture
    Severe     <1  Frequent bleeding episodes common, predominantly into joints & muscles.  Bleeding can occur spontaneously or after minor injury.
    Moderate    1-5 Can bleed after minor injury.  May have joint bleeding.  Severe bleeding with trauma, surgery, invasive procedures.
    Mild   >5-40 Bleeding with major trauma, surgery, invasive procedures.

    Ref: White GC et al. Definitions in Hemophilia: Recommendation of the Scientific Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.  Thromb Haemost 2001;85:560  

    Notify Haem Inpatient Registrar (pager 5030) of patients presenting to Emergency between 0900-1700hrs, Monday to Friday. Notify Haematologist on call of patients presenting after hours with bleeding problems.

    Assessment

    • Check patient's RCH EMR problem list "overview", this will state:
      • Type of Haemophilia (Factor VIII or IX)
      • Patient's treatment product and plan
      • Presence of Factor VIII/IX inhibitors
    • Check if patient is on home prophylaxis program and has already received factor replacement.
    • Check if patient has an infusaport.
    • Assess bleed and treat promptly.  Prompt clotting factor replacement reduces pain and long-term consequences of bleeding.
    • Major bleeding or suspected bleeding in the head, neck, chest, GIT and abdominal regions should be treated with clotting factor immediately, even before assessment is complete.  Clotting factor replacement should not be delayed by diagnostic imaging. 
    • Assess site and extent of bleeding and the impact on function.

    Management

    • Most bleeds will require factor replacement except for bruises and minor soft tissue injuries that do not impact on function and mobility. 
    • Invasive procedures such as arterial puncture, lumbar puncture must only be performed after clotting factor replacement.
    • Do not give IM injections.

    1. Clotting factor replacement

    Recombinant clotting factor concentrates are the product of choice. Occasionally patients will be treated with plasma-derived concentrates for management of factor VIII/IX inhibitors.

    • Doses should be rounded up to the nearest vial size
    • Do not discard any product (use whole vial). e.g. 20 kg child requiring 30 units/kg factor VIII, give 750 units 
    • Specify product type and name e.g. 750 units Recombinant Factor VIII (Xyntha).  See table below for list of products

    Note that there are two recombinant Factor VIII (FVIII) products available. Whilst it is recommended that patients maintain treatment with their established brand of FVIII product, in an emergency situation administration of any brand of recombinant FVIII is acceptable.

    Product type

    Product name (Brand)

    Vial sizes (units) Comment

    Recombinant FVIII(8)

    Xyntha® 250, 500, 1000, 2000, 3000

    EMR problem list will indicate patient's treatment product.   

    Advate® 250, 500, 1000, 1500, 2000, 3000
    Recombinant FIX(9) Benefix® 250, 500, 1000, 2000, 3000  

    Plasma derived FVIII(8) and von Willebrand Factor

    Biostate® 250 FVIII units, 500 FVIII units, 1000 FVIII units
    Recombinant Factor VIIa Novoseven®RT 1mg, 2mg, 5mg Bypassing agent for patients with Factor VIII or Factor IX inhibitors.
    Factor VIII Inhibitor Bypassing Agent (Plasma derived) FEIBA-NF® 500, 1000, 2500 Bypassing agent for patients with Factor VIII or Factor IX inhibitors. 

    Instructions for preparation and administration of clotting factor concentrates

    Recommended dosage of Factor VIII & Factor IX

    Type of bleed Haemophilia A  Haemophilia B  Comment
      Recombinant FVIII(8) Recombinant FIX(9)  
    Joint 40 units/kg Day 1 

    20 units/kg or usual home
    prophylaxis dose Day 2 & 4
    50 units/kg Day 1
     
    25 units/kg or usual home prophylaxis dose Day 2 & 5
    Factor replacement may be modified when intravenous access is difficult, particularly in toddlers.  E.g. 40 units/kg Day 1 & Day 2. Intravenous cannula may be left insitu with patient returning for Day 2 dose. (As an outpatient, intravenous cannula should not be left insitu for > 24 hours.) 
    Muscle (minor) 30 units/kg 50 units/kg  
    Muscle (major) 50 units/kg 75 units/kg Calf and forearm bleeds may lead to compartment syndrome and be limb threatening.  Arrange haematology and surgical review. Involvement of ileopsoas muscle may be associated with significant blood loss and mandates haematology review. 
    Oral Mucosa & Dental 30 units/kg 50 units/kg Antifibrinolytic therapy is critical.
    Epistaxis (active) 30 units/kg 50 units/kg Apply local measures (pressure).  Antifibrinolytic therapy effective in preventing recurrence.
    Gastrointestinal 50 units/kg 75 units/kg Haematology and gastroenterology review required.  Lesion is usually found. Antifibrinolytic therapy may be helpful.
    Genitourinary 50 units/kg 75 units/kg Evaluate for all causes however lesion not usually found.  Antifibrinolytic therapy contraindicated in haematuria.
    CNS/head 75 units/kg 125 units/kg Always treat with factor replacement prior to CNS imaging. Haematology & Neurosurgical review.
    Trauma or surgery 50 - 75 units/kg 75 - 125 units/kg Consultation with haematologist essential.

    2. Inhibitors to Factor VIII or IX

    • In haemophilia, inhibitors refer to IgG antibodies that neutralize a clotting factor
    • The presence of a new inhibitor should be suspected in any patient who fails to respond clinically to adequate factor replacement, particularly if the patient has been previously responsive
    • The incidence of inhibitor development in severe haemophilia A is approximately 20-30%
    • The incidence of inhibitor development in haemophilia B is < 5%
    • Up to 50% of haemophilia B patients with inhibitors may have severe allergic reactions, including anaphylaxis, to FIX administration. Such reactions can be the first symptom of inhibitor development
    • Consult with clinical haematology if an inhibitor is suspected

    3. Treatment of patients with inhibitors to Factor VIII or IX

    • Treatment and prevention of bleeding in patients with inhibitors is managed with bypassing agents such as Novoseven®RT or FEIBA®
    • Patients with a known inhibitor will have an individual management plan (refer to the patient’s EMR problem list)
    • Novoseven®RT and FEIBA® should never be administered concurrently due to the risk of thrombosis (there should be a 12 hour gap between Novoseven®RT and FEIBA® administration)
    • Use of antifibrinolytics (e.g. tranexamic acid) in combination with Novoseven®RT or FEIBA-NF® is relatively contra-indicated due to the risk of thrombosis
    • Management of inhibitor patients is complex, consultation with Clinical Haematology is essential

    Recommended dosage of Haemophilia inhibitor Bypass Agents:

    Inhibitor treatment product type  Inhibitor treatment product name   Dosage
     Recombinant activated factor VII (7)  Novoseven®RT  
    • 90 microgram/kg IV bolus every 2 hours until haemostasis achieved, then wean frequency
    • Consider 180 microgram/kg in major injury or bleeding not responding to 90 microgram/kg
     Plasma derived factor II and factor Xa  FEIBA-NF®  
    • Usually 50—100 units/kg every 12 hours
    • Maximum single dose 100 units/kg
    • Maximum daily dose 200 units/kg


    4. Bleeds requiring admission

    • Suspected intracranial haemorrhage
    • Bleeding into neck/throat
    • Forearm/calf bleed with suspicion or evidence of compartment syndrome
    • Bleeding into hip or inguinal area, suspected ileopsoas haemorrhage
    • Undiagnosed abdominal pain
    • Persistent haematuria
    • Bleeds causing severe pain

    5. General measures - joint and muscle bleeds

    For muscle and joint bleeds R.I.C.E.S will limit bleeding and reduce pain. Initiate on arrival.

    • P = Protection (immobilise affected area in position of comfort eg splint/sling/crutches)
    • R = Rest (in position of comfort)
    • I = Ice (Cold pack to reduce bleeding and pain)
    • C = gentle Compression bandage
    • E = Elevation 

    6. Venous access

    • Venous access is a major fear and stressor for children with haemophilia and their parents.
    • Children with haemophilia will require frequent venous access, minimisation of unsuccessful venepuncture and related distress is essential
    • Use distraction and relaxation techniques and consider nitrous oxide sedation. Ask parents about their preferred method for comforting/distracting their child
    • Patients with haemophilia are at risk of venepuncture related bleeding
    • Treat veins with care, apply pressure for at least 3 minutes post venepuncture.

    7. Analgesia

    • Paracetamol may be sufficient, however morphine or tramadol can be used for severe pain
    • Splinting/immobilisation is an effective adjunct for reducing pain
    • Do not use products containing aspirin or NSAIDS (e.g. ibuprofen, diclofenac)

    8. Desmopressin (DDAVP)

    • Releases stored Factor VIII (and von Willebrand factor) into the circulation. 
    • Used in patients with mild haemophilia A where there is documented evidence in the medical record of safe and satisfactory response (Desmopressin challenge). At RCH Desmopressin challenge is performed from around 5 years of age.
    • Not adequate for haemostasis in major bleeding.
    • Generally not recommended in young children ( < 3 years) due to documented reports of hyponatraemia and seizures.  Relatively contraindicated in children with previous seizure disorders.
    • Fluid restriction is recommended in the 24 hour period following Desmopressin administration. As a guide, fluid intake should be restricted to approximately 80% of maintenance fluid intake (refer to RCH Clinic Practice Guidelines, Fluid Therapy).
    • Dose: 0.3 microgram/kg (max 20 microgram) stat
      • When required pre-operatively administer 30 minutes before procedure
      • Daily dosing could be considered for up to 3 doses. Tachyphylaxis may be a concern after 48 hours.
      • Recombinant factor VIII replacement may be required if bleeding not controlled with desmopressin.
    • Administration: via intravenous infusion or subcutaneous injection
      • Intravenous infusion: dilute to a final volume of 50 mL with Sodium Chloride 0.9% and infuse over at least 30 minutes.
      • Subcutaneous injection: apply pressure to the site for 1 to 2 minutes post injection.
    • Presentation:
      • 4 microgram/mL injection (Minirin®).
      • 15 microgram/mL injection (Octostim®). Octostim® is preferred for subcutaneous injection due to its higher concentration.

    9. Antifibrinolytic therapy (tranexamic acid)

    • Reduces breakdown of blood clots and is effective for treating and preventing recurrence of mouth bleeds and epistaxis.
    • Contraindicated for treatment of haematuria
    • Dose of tranexamic acid (500mg tabs) 25mg/kg/dose (max:1.5g/dose) tds orally for 5-7 days
    Weight (kg) Tranexamic acid
    < 20 250 mg tds
    20 - 30 500 mg tds
    30 - 40 750 mg tds
    > 40 1 g tds

    10 Follow up

    • Referral to physiotherapist for joint and muscle bleeds is essential. Following joint/muscle bleeds, the affected area should be rested (immobilised/non weight bearing) for a minimum of 48 hours. Rehabilitation should commence as soon as pain and swelling has resolved
    • Please ask families to make contact with the Haemophilia team on the next working day for a telephone review 9345 5099
    • Joint/muscle bleeds will require follow up in haemophilia clinic