Successful Treatment of Bleeding in Acquired Hemophilia A with Activated Prothrombin Complex Concentrate in Spain

INTRODUCTION. Acquired hemophilia A (AHA) is a rare autoimmune disorder characterized by development of autoantibodies against coagulation factor VIII (FVIII). Bypassing agents are recommended as first-line for the treatment of bleeding episodes in patients with AHA. Due to the low incidence of AHA, available clinical data on efficacy and safety of the activated prothrombin complex concentrate (aPCC) in patients with AHA are limited. The objective of this retrospective multicenter study was to detail AHA management in patients treated with aPCC in real life in Spain.

METHODS. Data from patients with AHA, treated in any moment with aPCC, in five reference centers for coagulopathies disorders, between June 2012 and June 2017, have been collected.Bleedings were classified as initial (first episode after AHA diagnosis or relapse), concurrent (new bleeding at the same time but at a different anatomical location), subsequent (a new bleed recurring 72 hours after the resolution of the previous bleed) or re-bleed (same anatomical location within 72 hours of the resolution of the previous bleeding). Severity of the bleed was evaluated according the Word Health Organization scale. Hemostatic efficacy was assessed as bleeding cessation and pain control. Safety was evaluated during bypassing agent treatment and until 30 days after discontinuation.

RESULTS . Ten patients (6 males), 40% idiopathic AHA, median aged 70 years (64-84, IQR) at diagnosis. Seven patients out of 10 had at least 1 thrombotic risk factor, but no history of thrombotic events previous AHA. The median baseline residual FVIII level was 1% (0-1%, IQR), the median inhibitor titer was 24 BU (9-40, IQR).

In all cases the suspected diagnosis of AHA was precipitated by a bleeding event (combined with a prolonged aPTT in 7 patients). Suspected diagnosis came from hematology (80%), emergency room (10%) and internal medicine (10%). The diagnosis was made promptly by hematology after the suspicion at a median of 1 day (0-7, IQR). 10 patients presented 19 bleedings (13 initial, 4 subsequent, 1 concurrent, 1 re-bleed) (WHO severity: grade 1, n=1; grade 2, n=5; grade 3, n=12; grade 4, n=1) that were recorded. 84% of these bleedings arose spontaneously, 44% of them manifested primarily as muscle hematomas. There was emergency surgery because of acute abdominal surgey complication. Seventeen bleedings were treated with aPCC as first line (n=11) or second line after rFVIIa (n=6), achieved bleeding cessation and pain control in the 100% of the evaluated bleeding episodes. The mean initial dose per infusion was 54.4 (± 12.9 SD) U/kg, the median total dose was 48000 U (32000-68000 U, IQR), the initial dosing interval was 8 hours (8-12, IQR), the median duration of treatment was 5.5 days (3.5-10.5 days, IQR), and the median number of injections was 15 (7.5-21, IQR). No adverse events, including thromboembolic events, were described during aPCC treatment. A 75-years-old female patient died due to a severe respiratory insufficiency after 19 days of aPCC discontinuation. The reasons to change from rFVIIa to aPCC were non bleeding control in 2 patients and necessity to reduce the number of infusions per day for ambulatory management in the rest. All patients received first line immunosuppressive therapy: prednisone 1 patient, corticosteroids plus cyclophosphamide 7 patients, rituximab plus other immunosuppressive drug 2 patients. Patient with prednisone alone and one with rituximab plus esteroides needed a second line treatment for no response after more than 4 weeks. Median time to response in the group of corticosteroids plus cyclophosphamide was 56.5 days (40-108, IQR), rituximab plus other immunosuppressive drug 56.5 days (50-56.5 days, IQR).

CONCLUSIONS . This is the first study providing information on the daily use of aPCC in the treatment of AHA in Spain. With a hemostatic efficacy rate of 100% and a good safety profile, in line with other published real-life data. This multicenter Spanish experience supports the role of aPCC as first-line treatment for bleedings in AHA.