Haemophilia


  • Statewide logo

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

  • See Also

    Von Willebrand disease 

    Find a haemophilia treatment centre 

    Haemophilia Foundation Australia 

    National Haemophilia Guidelines

    Key Points

    1. All children with Haemophilia and a suspected bleed or requiring a procedure, should be discussed with their haemophilia treatment centre or associated on call haematologist.
    2. Assessment and investigation should not delay factor replacement.

    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.

    Classification 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.

    Assessment

     History

    • Determine type of haemophilia (Factor VIII or IX), the child's treatment product and plan, presence of Factor VIII/IX inhibitors
    • Check if the child is on home prophylaxis program and most recent dose of factor.

    Examination

    • Assess site and extent of bleeding and the impact on function.
    • Major bleeding or suspected bleeding in the head, neck, chest, GIT and abdominal regions should be treated with clotting factor immediately, even before full assessment is complete. 

    Management

    Investigations

    Routine coagulation studies are not required.

    Imaging

    • Clotting factor replacement should not be delayed by diagnostic imaging.
    • The need for imaging is dependent on mechanism of injury (trauma).

    Treatment

    • Most bleeds will require factor replacement except for bruises and minor soft tissue injuries that do not impact on function and mobility. 
    • Prompt clotting factor replacement reduces pain and long-term consequences of bleeding.
    • Invasive procedures such as arterial puncture, lumbar puncture must only be performed after clotting factor replacement.
    • Do not give IM injections.
    • All children should be discussed with their haemophilia treatment centre or associated on call haematologist.

    1. Clotting Factor Replacement

    Recombinant clotting factor concentrates are the product of choice. Occasionally children 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 
    • When ordering product, specify product type and brand name and units 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 children 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

     

    Advate®

    250, 500, 1000, 1500, 2000, 3000

    Recombinant FIX(9)

    Benefix®

    250, 500, 1000, 2000, 3000

     

    Plasma derived FVIII(8) & von Willebrand Factor

    Biostate®

    250 FVIII units
    500 FVIII units
    1000 FVIII units

    Recombinant Factor VIIa

    Novoseven®RT

    1mg, 2mg, 5mg

     

    Bypassing agent for children with Factor VIII or Factor IX inhibitors.

    Factor VIII Inhibitor Bypassing Agent (Plasma derived)

    FEIBA-NF®

    500, 1000, 2500

    Bypassing agent for children with Factor VIII inhibitors.

    Instructions for preparation & 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 the child 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

    Superficial muscle with no neurovascular compromise

    Muscle (major)

    50 units/kg

    75 units/kg

    Deep muscle where there are signs or suspicion of neurovascular compromise or substantial blood loss.


    Iliopsoas muscle.


    Calf and forearm bleeds may lead to compartment syndrome and be limb threatening.  Arrange haematology and surgical review.


    Involvement of iliopsoas 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. Treatment of children with inhibitors to Factor VIII or IX

    • Management of inhibitors is complex, consultation with the Haemophilia treatment centre or associated on call Haematologist is essential.
    • In haemophilia, inhibitors refer to IgG antibodies that neutralize clotting factor
    • The presence of a new inhibitor should be suspected in any child who fails to respond clinically to adequate factor replacement, particularly if the child has been previously responsive
    • Up to 50% of haemophilia B children with inhibitors may have severe allergic reactions, including anaphylaxis, to FIX administration. Such reactions can be the first symptom of inhibitor development
    • Treatment and prevention of bleeding in children with inhibitors is managed with bypassing agents such as Novoseven®RT or FEIBA®. 
    • 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

    Recommended dosage of Haemophilia inhibitor Bypass Agents

    Inhibitor treatment product type

    Inhibitor treatment product name

    Indication

    Dosage

    Recombinant activated factor VII (7)

    Novoseven®RT

    Haemophilia A with inhibitor
    Haemophilia B with inhibitor

    • 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®

    Haemophilia A with inhibitor

    • Usually 50—100 units/kg every 12 hours
    • Maximum single dose 100 units/kg
    • Maximum daily dose 200 units/kg


    3. General Measures - Joint and Muscle Bleeds

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

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

    4. 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.
    • Children with haemophilia are at risk of venepuncture related bleeding
    • Treat veins with care, apply pressure for at least 3 minutes post venepuncture.

    5. Analgesia

    • Paracetamol may be sufficient, however morphine and 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)

    6. Desmopressin (DDAVP) in mild haemophilia

    • Releases stored Factor VIII (and von Willebrand factor) into the circulation. 
    • Used in children 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.

    7. Antifibrinolytic Therapy (tranexamic acid)

    • Reduces breakdown of blood clots and is effective for treating and preventing recurrence of mouth bleeds and epistaxis in all severities of haemophilia.
    • 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

    Consider consultation with local paediatric team when:

     All children with Haemophilia and a suspected bleed or requiring a procedure, should be discussed with their haemophilia treatment centre or associated on call haematologist 

    Consider transfer when:

    All children with

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

    Children requiring care beyond the level of comfort of the local hospital or treating medical team.

    For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650.

    Consider discharge when:

    In consultation with haemophilia treatment centre or associated on call haematologist.

    Recovery and prevention of re-bleed

    • Please ask families to make contact with the Haemophilia treatment centre on the next working day
    • For recovery and prevention of re-bleed
      • 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 have resolved.
      • Joint/muscle bleeds will require follow up in haemophilia clinic

    All Children with haemophilia in Victoria are managed through RCH Melbourne Haemophilia Treatment Centre. 

    Clotting factor concentrates are not routinely available in all hospitals.

    Patients in metropolitan Melbourne should attend RCH for treatment of bleeding episodes.

    Patients in regional/rural areas that are likely to require treatment will have a supply of their factor concentrate at home and/or at their local hospital (organised by their haemophilia treatment centre). 

    • The GP/paediatrician/blood bank/pharmacy will be informed when factor concentrate is held in a regional/rural hospital for a patient.
    • Patients presenting to a regional/rural hospital with bleeding should be discussed with their haemophilia treatment centre or associated on call haematologist and transferred if ongoing treatment with factor concentrates are required.

    Information specific to RCH

    Check the child’s EMR problem list ‘overview’ for type of haemophilia, treatment product and plan, presence of Factor VIII/IX inhibitors.

    Notify Haematology Inpatient Registrar (pager 5030) of children presenting to Emergency between 0900-1700hrs, Monday to Friday.

    Notify Haematologist on call of children presenting after hours with a suspected bleed or requiring a procedure.

    Please ask families to make contact with the Haemophilia treatment centre on the next working day for a telephone review (03 9345 5099).  Joint/muscle bleeds will require follow up in haemophilia clinic.  


    Last updated June, 2018