Von Willebrand Disease vWD

  • See also: Haemophilia

    Background

    The most common inherited bleeding disorder affecting 0.1 - 1% of the population. Caused by a deficiency (either quantitative or functional) in von Willebrand Factor (vWF).  Deficiency of vWF causes inadequate platelet adhesion and secondary deficiency of Factor FVIII. Affects males and females equally.

    Characterised by easy bruising, bleeding from mucous membranes (particularly epistaxis, oral mucosa, menorrhagia) and post-op bleeding.

    There are three main phenotypes of vWD.

      vWF problem Typical bleeding picture
    Type 1 (common) Reduced levels of vWF Typically associated with mild bleeding
    Type 2 (uncommon) Abnormal structure and function of vWF, several variants Variable bleeding pattern
    Type 3 (rare) Near absence of vWF Patients may behave like those with moderate to severe haemophilia

    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

    Assess site and extent of bleeding.

    Assess type and severity of vWD, if known. Refer to the RCH Emergency Department alert system for individual treatment plan.

    Management

    Antifibrinolytics (Tranexamic acid)

    • Often helpful for mucosal bleeding (most common form of bleeding) - mouth, epistaxis, menorrhagia.  
    • May be given alone or as adjunct therapy to Desmopressin/factor concentrate.
    • 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

    Desmopressin (DDAVP)

    • Patients with mild to moderate Type 1 vWD can be treated with Desmopressin when there is documented evidence in the medical record of safe and satisfactory response (Desmopressin challenge). At the RCH Desmopressin challenge is performed from around 5 years of age.
    • Occasionally effective in Type 2 vWD, never effective in Type 3 vWD.
    • Expect two to three fold increase in Factor VIII/vWF level.
    • 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.
      • Plasma derived Factor VIII/vWF (Biostate®) 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.

    Von Willebrand Factor/FVIII Plasma Concentrate (Biostate®)

    • A human plasma-derived product, available from blood bank
    • May be required in Type 1 vWD if severe bleeding or unresponsive to DDAVP
    • Used to treat bleeding in patients with Type 2 and Type 3 vWD.  
    • Each reconstituted vial of Biostate® contains 50 IU/ml FVIII and 100 IU/ml von Willebrand factor
    • Note that recombinant FVIII products do not contain von Willebrand factor

    Recommended dosage

    Please note that the vial will state both Factor VIII and von Willebrand Factor units.
    Check that dosage is according to Factor VIII units,eg prescribe as 'Biostate® 2000 Factor VIII units'.

    If there is uncertainty regarding correct dosage please contact Haem Inpatient Registrar (pager 5030) between 0900-1700hrs, Monday to Friday or Haematologist on call (via switch) after hours.

    Type of bleeding Dose of Biostate®
    Oral mucosa/epistaxis/menorrhagia 25 Factor VIII units/kg (=50 von Willebrand Factor units/kg)
    GI/GU bleed 40 Factor VIII units/kg (=80 von Willebrand Factor units/kg)
    Joint/Muscle 40 Factor VIII units/kg (=80 von Willebrand Factor units/kg)
    CNS bleed 60 Factor VIII units/kg (=120 von Willebrand Factor units/kg)
    Trauma or surgery 60 Factor VIII units/kg (=120 von Willebrand Factor units/kg)

    Notes

    Please ask families to make contact with the Haemophilia Nurse on the next working day for a telephone review.
    Instructions for preparation and administration of Clotting factor products