Recombinant Factor VIIa (rFVIIa) Is Safe and Effective When Used to Treat Acute Bleeding Episodes and to Prevent Bleeding During Surgery in Patients with Acquired Hemophilia: Updated Assessment From the Hemostasis and Thrombosis Research Society (HTRS) Registry AH Database,

Acquired hemophilia (AH) is a rare disorder marked by the development of autoantibodies to factor VIII, with associated mortality of 8–22%. Patients present with bleeding episodes or unexpected bleeding at surgery, and a prolonged aPTT that does not correct with 1:1 mixing (2 hrs, 37°C). While the antibody often resolves with immunosuppression, most patients will need hemostatic treatment with bypassing agents including rFVIIa (NovoSeven RT) to resolve bleeding episodes or prevent bleeding during surgery.

Data were analyzed from the HTRS registry (January 2004 – July 2011), supporting rFVIIa post-marketing surveillance, including data entered during the past 2 years on acute bleed and new surgical case report forms.

Of 154 identified AH patients, 99 had 217 reported bleeds and 35 underwent 56 surgical procedures. There were 125 (58%) rFVIIa-treated bleeds: 82 rFVIIa alone, 43 rFVIIa plus other agents/blood products, and 107 (86%) first-line rFVIIa therapy. For rFVIIa-treated bleeding episodes, 65 (52%) were in males and 60 (48%) in females; 85 were in white-non Hispanics and 24 (19%) in black non-Hispanics. Mean (median) age at bleeding was 66 (68) years. Median (range) of recent inhibitor titer was 16 (0–620) BU. Bleeds were spontaneous (85), traumatic (27), surgical/procedure-related (7), dental (2) or other (3). rFVIIa bleed treatment over a median 1 (range 1–60) day(s) are shown below:

Efficacy of rFVIIa (physician-rated for each regimen), was reported as “bleeding stopped” in 105 (84%) episodes; “bleeding slowed” in 14 (11%) episodes (stopped with other agents in 3 episodes); “no improvement” in 5 (4%) episodes (no bleed stop date identified in 4, stopped with other agent in 1), and was not documented in 1. Excluding the 4 rFVIIa treatment failures where bleeding stopped after switching to another agent, overall rFVIIa efficacy was 97%. The only thromboembolic event was in a post-partum patient with transient neurologic symptoms.

Of 56 surgical procedures ranging from minor procedures to major surgeries, 24 (43%) were rFVIIa-treated procedures (17 rFVIIa only). The 17 rFVIIa-treated patients had a mean (range) age of 72.4 (28–89) years, and were mostly in female and white non-Hispanic patients. Surgeries included central venous access (6), endoscopy (5), incision, drainage and grafting of hand hematomas (3), embolization of AVM (2), orthopedic procedures (2), cholecystectomy (1), colon biopsy (1), catheter removal (1), exchange of prostate treatment implant (1), venipuncture (1) and IVC placement (1). rFVIIa was used prior to surgery in 19 procedures and post-operatively in 15. rFVIIa treatment parameters are shown below:

A single dose was used in 8/24 surgeries; maximum treatment was 19 days. Efficacy of any bypassing agents was rated as excellent/good or fair/partially effective in 20/24 (83%) procedures. Adequate hemostasis was achieved with planned regimens (all agents) in 16 procedures, with minor rFVIIa dose increases in 3, with additional agents in 2 (1 each PRBCs and Helixate), and “other” reported for 1. There were no thromboembolic events (TEs) reported.

The HTRS registry now represents the 2^nd largest data set reporting rFVIIa use in AH with 75% increase in rFVIIa-treated bleeds in the past 2 years, and is the only one to report data gathered on minor and major surgical procedures in AH. For acute bleeds and surgeries, median rFVIIa dosing was similar to doses recommended for routine treatment of bleeding episodes in patients with autoantibody inhibitors based on published studies. As AH surgeries are uncommon, we believe the surgeries reported relate to bleeding sites or venous access. No safety concerns were reported in this older population. As this registry was originally intended in part to track the safety of rFVIIa, these derived data may be somewhat biased and selective. Nevertheless, the data certainly indicate that rapid and safe hemostasis can be achieved for acute bleeding episodes and prevention of excessive bleeding during surgery with rFVIIa in an aging population where thrombogenicity is of concern.

Ma:Novo Nordisk Inc.: Consultancy. Kessler:Novo Nordisk Inc.: Consultancy. Gut:Novo Nordisk Inc.: Employment. Cooper:Novo Nordisk Inc.: Employment.