Treatment of Acute Bleeds in Acquired Hemophilia: An Updated Analysis From the Hemophilia and Thrombosis Research Society (HTRS) Registry.

Abstract 3499

Poster Board III-436

Acquired hemophilia A (AH) is a rare disorder marked by the development of auto-antibodies to factor VIII. Patients present with a prolonged aPTT that does not correct with mixing and clinically evident bleeding. The Hemophilia and Thrombosis Research Society (HTRS) registry is maintained to study treatment strategies for hemophilia and related disorders in the US. Prior analysis of data resulted in the identification of 25 patients with 29 acute bleeds recorded. An expanded and updated analysis is now presented of treatment patterns for acute bleeds in patients with AH.

In total, 90 patients were identified in HTRS, 51 of whom had 138 reported bleeding episodes. Of these, 71 bleeds (51%) were treated with recombinant Factor VIIa (rFVIIa), including 49 bleeds treated with rFVIIa alone and 22 with rFVIIa plus other agents or blood products. In addition, 51 (37%) bleeds were treated with other agents including aPCC (Autoplex T: 19 bleeds, FEIBA: 13 bleeds), aPCC and blood products (7 bleeds), blood products alone (8 bleeds), and FVIII (2 bleeds). 14 episodes did not require treatment for acute bleeds, and 2 had no treatment data recorded. Of patients with bleeds, there were 28 males and 22 females; 36 were Caucasian and 13 African-American. Mean (median) age at time of bleed was 69 (76) years.

For those treated with rFVIIa, median (range) initial dose was 91.2 (22-270) mcg/kg, median dose per infusion was 91.0 (22-270), and total treatment dose per bleeding episode was 536.1 (22-18,000)) mcg/kg. Total number of rFVIIa doses was 4 (1-240) for a median of 1 (1-60) day and total treatment duration of 1 (1-60) day for the entire bleeding episode. Dosing data is not available for aPCC.

Efficacy was rated by the physician at 72 hours. In patients using rFVIIa, effectiveness was rated as the bleeding stopped in 53/71 episodes (75%); bleeding slowed in 13/71 episodes (no other agents given for 8 episodes, no bleed stop date identified in 3 and the bleed stopped with other agents in 2), bleeding stopped but a re-bleed occurred in 48 hours for 1 episode (no other agents given), no improvement in 3 episodes (no bleed stop date identified in 2, and switched to other agent in 1). Overall rFVIIa efficacy including complete and partial response was 93%. rFVIIa was used as first line therapy in 63 episodes, and as second line therapy in 8. rFVIIa treatment failure, in which the bleed responded to an alternative agent, was 3/71 (4.2%) episodes. Treatment results were not documented for 1 episode. In patients using aPCC, the bleeding stopped in 28/38 episodes (74%); bleeding slowed in 5/38 episodes (no other agents given), and there was no improvement in 5 episodes (no other agents given). Overall aPCC efficacy including complete and partial response was 87%. aPCC treatment failure was 2/45 (4.4%). Of note, 15% of rFVIIa and 50% of bleeds treated with aPCC occurred in 1 patient.

Reported adverse events with rFVIIa were rare. One 31-year-old patient with pre-eclampsia and bleeding after a Caesarean section experienced transient neurologic symptoms after receiving rFVIIa 90 mcg/kg q2h for 113 consecutive doses; a cerebral MRI showed multifocal ischemia. No thrombotic complications were reported in 3 individuals treated with higher dose rFVIIa (160,180, 270 mcg/kg). AE data for other agents is not available.

While registry data can only demonstrate the treatment captured in selected bleeds reported, this significantly expanded HTRS registry now represents the 2^nd largest data set reporting factor use in AH. Treatment of AH has also been documented in recent registries outside the US (e.g. EACH2, SACHA). The current analysis demonstrates rFVIIa and aPCC effectiveness consistent with prior reports. The registry suggests that failures to conventional dosing may respond to very high dosing for rFVIIa without sacrificing safety. As this registry was originally intended in part to track the safety of rFVIIa, these derived data may be somewhat biased and selective. Nevertheless, they are certainly indicative that rapid and safe hemostasis can be achieved in an aging adult population where thrombogenicity of hemostatic agents is of major concern. This registry will continue to collect data on AH patients to determine whether treatment and dosing trends change as experience with rFVIIa expands. In addition, these expanded data support HTRS as a suitable platform to assess other critical management issues (e.g. immune tolerance) within the AH population in the future.