Acquired inhibitors against coagulation factor VIII (FVIII), also termed
acquired haemophilia A, neutralize its procoagulant function and result in
severe or often life-threatening bleeding. The antibodies arise in
individuals with no prior history of clinical bleeding. Acquired haemophilia
occurs rarely with the incidence of approximately 1 to 4 per million/ year,
with severe bleeds in up to 90% of affected patients, and high mortality
between 8-22%. About 50% of diagnosed patients were previously healthy, while
the remaining cases may be associated with postpartum period, autoimmune
diseases, malignancy, infections, or medications. Most patients have
spontaneous haemorrhages into the skin, muscles or soft tissues, and mucous
membranes, or after trauma and surgery, whereas haemarthroses are uncommon.
The diagnosis of acquired haemophilia A based on the prolongation of
activated partial thromboplastin time which does not normalize after the
addition of normal plasma, reduced FVIII, with evidence of FVIII inhibitor
measured by the Bethesda assay (Nijmegen modification). The treatment of
acute bleeding episodes and the long-term eradication of the autoantibodies
in acquired haemophilia are the main therapeutic strategy. Two options are
currently available for acute bleeding control: the use rFVIIa or FEIBA in
patients with higher inhibitor titer (>5 BU), or to raise the level of FVIII
by administration of DDAVP or concentrates of FVIII in patients with low
level of inhibitors (<5 BU). Treatment with FEIBA (50-100 IU/ kg every 8-12
hours) has shown good haemostatic response in 76-89% of the bleeding
episodes. Patients treated with rFVIIa (90 ?g/kg every 2-6 hours) have
achieved good response in 95-100% as a first-line, and 75-80% as a salvage
therapy. Patients with low inhibitor titer and lower response can be treated
with concentrate of FVIII in the recommended dose of 40 IU/kg plus 20 IU/kg
for each BU of inhibitor. The treatment of non-life-threatening haemorrhages
with desmopressin (DDAVP 0.3 ?g/kg) may increase both FVIII and vWF.
Sometimes inhibitors disappear spontaneously, but longterm management is
necessary for eradication of inhibitors by immunosuppression (prednisone 1
mg/kg 3 weeks alone or in combination cyclophosphamide 2 mg/kg),
immunomodulation, intravenous immunoglobulin (HD IgG 2g/kg 2 or 5 d),
physical removal of antibodies (plasmapheresis or immunoadsorption), or
various combinations. Recently, a therapy with rituximab, an anti-CD20
monoclonal antibody, has shown to be effective in acquired haemophilia.
Acquired haemophilia syndrome: Pathophysiology and therapy
