US Experience with Recombinant Factor VIIa (rFVIIa) for Surgery in Acquired Hemophilia (AH): Analysis From the Hemophilia and Thrombosis Research Society (HTRS) Registry

Abstract

3372 Background: AH is a rare disorder caused by autoantibodies against factor VIII (FVIII). Patients can present with peri-operative bleeding, and a prolonged aPTT that doesn't correct with 1:1 mixing after 2 hours (37°C). The Hemostasis and Thrombosis Research Society (HTRS) Registry was established to support the society's research needs and monitor the safety of recombinant activated factor VII (rFVIIa). In October 2006, the FDA approved rFVIIa for the treatment of bleeding and prevention of bleeding during surgery in AH at 70–90 mcg/kg every 2–3 hours. In 2007, a new case report form (CRF) for capturing information about surgeries was added. Methods: Data on treatment during surgical procedures was collected from the HTRS registry surgical CRF. For each rFVIIa-treated surgery, the initial dose, total dose per procedure (prior to and post surgery), average infused dose, number of doses, and treatment duration were calculated. Queries were issued to verify any procedures lacking treatment data or where treatment was listed as “none”. Efficacy was assessed on a 4 point scale and an investigator assessed adequacy of hemostasis on the “planned regimen” immediately and at 24 and 72 hours. Results: Of 166 registered AH patients, 36 patients underwent 58 surgeries. There were 24 (43%) rFVIIa-treated procedures (17 rFVIIa only). The mean (range) age of all patients undergoing surgery was 69 (14–89), and for rFVIIa-treated patients was 77.8 (28–89). rFVIIa-treated patients were mostly female (71%) and Caucasian (59%). Approximately 33% (19/58) of all surgeries were elective, including 54% (13/24) of rFVIIa-treated surgeries. The most common procedures overall were central line placement (12), endoscopy (12) and orthopedic (5). rFVIIa-treated surgeries included: central venous access (6), endoscopy (5), incision, drainage and grafting of hand hematomas (3), AVM embolization (2), orthopedic procedures (2) cholecystectomy (1), colon biopsy (1), catheter removal (1), exchange of prostate brachytherapy implant (1), venipuncture (1) and IVC filter placement (1). rFVIIa was used pre-op in 19 procedures and post-surgery in 15. In 9/24 procedures (8/24 pre-op), a single rFVIIa dose was used. Median (range) for rFVIIa treatment is described in the table below: rFVIIa efficacy was rated as excellent/good in 17 (77.3%), fair/partially effective in 2 (9.1%), and poor/ineffective in 3 (13.6%). For those rated fair/partially effective, one received only one pre-op rFVIIa dose of 75 mcg/kg with antifibrinolytics (no post-surgery treatment) and the other received 1 pre-op and 2 post-op rFVIIa 106 mcg/kg doses at 2 hour intervals with no other treatments. For those rated poor/ineffective, one received rFVIIa and PRBCs only, one received rFVIIa 81 mcg/kg initially every 4–6 hrs then plasma-derived activated prothrombin complex concentrate (pd-aPCC) then rFVIIa, and one had resolution of a neck hematoma with rFVIIa (subsequently switched to pd-aPCC) but could not maintain an airway and was transferred to hospice. No thromboembolic events were reported in rFVIIa-treated patients. Two patients underwent 6 follow-up procedures during ongoing post-op rFVIIa-treatment. Eleven patients used hemostatic agents other than rFVIIa in 12 surgical procedures. These included use of pd- aPCC in 5 cases (3 pre-op; 2 pre-op and post-op) and use of desmopressin in 2 cases, and recombinant FVIII in 3 cases. Blood products (FFP, PRBCs) were used post-op in 2 cases. Thirteen patients underwent 16 surgeries with no reported treatment. Conclusions: rFVIIa provided adequate hemostasis for almost all rFVIIa-treated AH surgeries at doses largely conforming to the package insert. There were no safety concerns and no thromboembolic complications reported in this population of older patients. Lack of hemostatic therapy reported for some procedures may reflect surgery as a presenting AH symptom, surgery during ongoing treatment not requiring additional treatment, or surgery performed following immune suppression/tolerization. Disclosures: Ma: Novo Nordisk Inc.: Consultancy, Speakers Bureau. Kessler:Novo Nordisk: Consultancy, Research Funding. Fisher:Novo Nordisk Inc.: Employment. Gut:Novo Nordisk Inc.: Employment. Cooper:Novo Nordisk Inc.: Employment.

Acquired haemophilia: an overview for clinical practice

“…More recently, preliminary data have been published on the favourable safety and efficacy profiles of rFVIIa in the surgical setting from the HTRS registry . This is a longitudinal US database established in 1999 to study treatment strategies for patients with bleeding disorders and monitor the postapproval use of rFVIIa, which since 2006 (date of approval of rFVIIa for AHA in the US) has provided postmarketing surveillance on rFVIIa‐treated patients with AHA.…”

“…This is a longitudinal US database established in 1999 to study treatment strategies for patients with bleeding disorders and monitor the postapproval use of rFVIIa, which since 2006 (date of approval of rFVIIa for AHA in the US) has provided postmarketing surveillance on rFVIIa‐treated patients with AHA. We await the full publication of the HTRS data set with interest.…”

Overcoming the diagnostic and monitoring challenges for very rare bleeding disorders in the US: the potential benefits of a centralized laboratory

“…The EACH‐2 registry captured data between 2003 and 2008 and included 501 patients with AH from 117 centres and included data on 474 bleeding episodes, follow‐up for post‐partum haemorrhage and outcomes of immunosuppression . The Hemostasis and Thrombosis Research Society (HTRS) registry captured data between 2000 and 2011 and included 166 patients with AH with 237 bleeding episodes and 58 surgical procedures .…”