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.

Postpartum acquired factor VIII inhibitors

“…The choice of the product depends on the severity of the bleeding and the FVIII inhibitor titers [12]. Thus, while clinically mild cases of acquired hemophilia with low-inhibitor titers can be managed successfully using DDAVP and FVIII concentrates [37,64,69,70,82], patients with high-titer FVIII antibodies and severe bleeding benefit from APCC and rFVIIa [60,70,73]. rFVIIa has been used successfully in the home treatment of patients with FVIII inhibitors, including postpartum cases [59].…”

“…Immunosuppressive agents other than cyclophosphamide (azathioprine, cyclosporine, 6-mercaptopurine) have been used less frequently for the management of postpartum FVIII inhibitors, but also appear to be effective [58,70]. Mazzucconi and colleagues [64] reported four cases of postpartum FVIII inhibitor treated with highdose immunoglobulins and dexamethasone: in 3 cases the combined therapy led to rapid eradication of the autoantibody. Stasi and colleagues [72] recently reported a complete remission in a case of postpartum acquired hemophilia A after treatment with rituximab and cyclophosphamide.…”

The use of recombinant activated factor VII in life‐threatening postpartum hemorrhage

“…Unpublished works were identified by searching the abstract books of the most important conferences on obstetric and hematological diseases. A total of 31 articles were retrieved from the literature search 22–52 …”

“…Table 1 analyzes in detail the studies. Our analysis of the published data identified 31 articles/abstracts including 97 patients with PPH receiving rFVIIa 22–52 . In those reports cesarean section is associated with an increased risk of onset of PPH as, among the 85 deliveries reported, 32 (37.6%) were by vaginal route and 53 (62.4%) by cesarean section.…”

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][3][4][5][6][7]. They can appear during pregnancy and the postpartum period [8][9][10].…”