Inhibitor Eradication in Postpartum Acquired Haemophilia A: Real-Life Case Series and Literature Review

Abstract

Background: Acquired haemophilia A (AHA) is a rare and severe bleeding disorder generally associated with pregnancy or aging. Spontaneous remission and prompt inhibitor eradication are described more frequently in postpartum cases. We evaluated retrospectively 15 postpartum AHA cases between 2007 and 2023 in order to evaluate response in terms of inhibitor eradication.

Results: The median age at diagnosis was 31 years (range 24-38). All patients reported bleeding at presentation after a median period of 40.6 days following delivery (range 2-180 days). The median FVIII level was 4.4% (range 0%-12.8%), with a median FVIII-inhibitor titer of 35 BU (range 2-156). The most severe bleeding symptoms were metrorrhagia and genital bleeding in nine patients (60%), and one patient had an important muscular haematoma. Two patients underwent hysterectomy before diagnosis due to severe bleeding. All patients required anti-haemorrhagic therapy with a median duration of 8 days (range 1-28 days): 60% (9/15) with eptacog alfa, two with an activated prothrombin complex concentrate, and in combination in four cases. The immunosuppressive treatment was corticosteroids alone in eight patients (53%), cyclophosphamide or azathioprine in combination with corticosteroids in four, while rituximab was used in two cases following traditional immunosuppressive therapy. After a median period of 28 days (range 10-210 days), the anti-FVIII inhibitor was eradicated with normalisation of coagulation in all but one patient. However, immunosuppressive therapy, including tapering, had a median duration of 2.3 months (range 1-23 months). At the time of data censoring, all patients were alive and well at the last follow-up with no significant adverse events.

Summary/conclusion: Notwithstanding that postpartum AHA has been reported to have a high rate of spontaneous remission, nearly half of this series experienced inhibitor eradication more than 1 month after disease onset and using immunosuppressive treatment for more than 2 months, with additional drugs being used in more than 40% of them, thus showing difficulties in disease remission in this postpartum AHA subpopulation.

Keywords: acquired haemophilia A; bleeding disorder; immunosuppressive therapy; inhibitor; postpartum.

FIGURE 1

Laboratory characteristics (FVIII levels, inhibitor titer) and time required for inhibitor eradication in women with post‐partum AHA.

FIGURE 2

Time to obtain FVIII‐inhibitor eradication in women with AHA (n = 15).

FIGURE 3

Duration of immunosuppressive treatment in women with post‐partum AHA (n = 15).

FIGURE 4

Time to eradication splitted for treatment in women with AHA (n = 15). CCS, corticosteroids; CTX, cyclophosphamide; AZT, azathioprine; RTX, rituximab.