Coagulation factor inhibitors (alloantibodies and autoantibodies), including acquired haemophilia, acquired von Willebrand syndrome, inhibitors to factor VIII in haemophilia A, and inhibitors to factor IX in haemophilia B

Version: 2.1
Published: 18 February 2016
Condition for which Ig use is in exceptional circumstances only

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Coagulation factor inhibitors
Level of Evidence Evidence of probable benefit – more research needed (Category 2a)
Management of these rare and severe bleeding disorders should be undertaken only by or in consultation with haemophilia treatment centres. When indicated, intravenous immunoglobulin (IVIg) only forms part of the management of these complex patients, with additional haemostatic support required.

IVIg may be considered in the following circumstances:
 
  1. Inhibitors to factor VIII (FVIII) in haemophilia A and inhibitors to factor IX (FIX) in haemophilia B, especially in cases where there has been failure of immune tolerisation and poor response to recombinant factor VIIa or factor eight inhibitor bypassing activity (FEIBA) — only as part of the Bonn–Malmö protocol for immune tolerance induction.
  2. Autoimmune acquired von Willebrand syndrome — correction of FVIII and von Willebrand factor levels for the management of bleeding and before invasive procedures, except cases associated with IgM paraprotein where response is unlikely. Use is indicated in failure to respond to chemotherapy/immunosuppressants or where there is insufficient time for chemotherapy/immunosuppressants to be given. Initial therapy either 0.4 g/kg for 5 days or 1 g/kg for 2 days. Continued therapy 1 g/kg once every 3–4 weeks.
  3. Acquired haemophilia A for:
    a. support of correction of FVIII level for the management of bleeding, and before invasive procedures in individuals in whom steroid or immunosuppressive therapy is contraindicated or has failed to eradicate the inhibitor (2 g/kg over 2–5 days); or
    b. support of correction of FVIII level following failure of first-line therapies (steroids and immunosuppressants) and poor response to recombinant factor VIIa or FEIBA when used as part of the Bonn–Malmö protocol.
  4. Other acquired (autoimmune) coagulation inhibitors (e.g. acquired Factor V inhibitors) to correct factor level for the management of bleeding and before invasive procedures in cases where other therapeutic approaches have failed or are contraindicated (2 g/kg over 2 to 5 days).
Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
 
Bibliography
Hay, CR, Brown, S, Collins, PW, et al 2006, ‘The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation’, British Journal of Haematology, vol. 133, no. 6, pp. 591–605.