Postpartum inhibitor to factor VIII: treatment with high‐dose immunoglobulin and dexamethasone

Abstract

Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare event. About 50% of cases are idiopathic. Among younger people, inhibitors are often found in the postpartum period. Treatment must be administered either to overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches have been proposed for inhibitor eradication, based on immunosuppressive drugs such as corticosteroids, cyclophosphamide and azathioprine, with varying results. High-dose immunoglobulin (HDIg) has been recently proposed as first-line therapy. We report on four cases with acquired inhibitor to FVIII occurring 4-8 months after delivery. At diagnosis, inhibitor titre was < 5 Bethesda units mL(-1) (BU mL(-1)) in three cases, and > 5 BU mL(-1) in one. Factor VIII coagulant activity (FVIII:C) was < 1 U dL(-1) in three cases and 12 U dL(-1) in one. We treated the patients with HDIg (400 mg kg(-1) day(-1) for 5 consecutive days) and dexamethasone (24 mg day(-1) for 5-7 consecutive days), administered at the same time. In three women, the inhibitor was suppressed in 2-50 weeks. After an off-therapy period ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the inhibitor undetectable. The fourth woman remained unresponsive. In two cases, recombinant activated factor VII administration stopped the bleeding. Thus, intermediate- to high-dose dexamethasone and HDIg given at the same time could be a successful and safe therapeutic approach for a rapid and complete remission from the development of FVIII inhibitors

The use of recombinant activated factor VII in obstetric and gynaecological haemorrhage

“…activated prothrombin complex concentrates and rFVIIa) in patients with high‐titre FVIII antibodies and severe bleeding 71,76 . There are few cases reported in literature on the use of rFVIIa in postpartum acquired haemophilia A 73,77–80 . Mazzucconi et al 80 described four postpartum inhibitor cases treated with high‐dose immunoglobulin and dexamethasone; in two women, bleeding symptoms were stopped by the concomitant use of rFVIIa at a dose of 90 microgram/kg every 12 hours for 4 days.…”

“…There are few cases reported in literature on the use of rFVIIa in postpartum acquired haemophilia A 73,77–80 . Mazzucconi et al 80 described four postpartum inhibitor cases treated with high‐dose immunoglobulin and dexamethasone; in two women, bleeding symptoms were stopped by the concomitant use of rFVIIa at a dose of 90 microgram/kg every 12 hours for 4 days. Other cases successfully treated with rFVIIa have been collected by Baudo and de Cataldo in the Register of acquired FVIII inhibitors from the Italian Association of Haemophilia Centres 73,77 .…”

Acquired factor VIII inhibitor in a non‐haemophilic boy

“…Autoantibodies to factor VIII occur in patients with autoimmune disorders, as well as benign lymphoproliferative diseases, leukaemia, lymphomas, asthma bronchiale and after administration of certain drugs [2–7]. They can appear during pregnancy and the postpartum period [8–10].…”