Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in haemophilia patients with inhibitors undergoing major surgery

Rajiv K. Pruthi; Prasad Mathew; Leonard A. Valentino; Michael J. Sumner; Stephanie Seremetis; Keith W. Hoots; the NovoSeven in Surgery Study Investigators; on behalf of

doi:10.1160/TH07-03-0198

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 726-732
DOI: 10.1160/TH07-03-0198

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in haemophilia patients with inhibitors undergoing major surgery

Results from an open-label, randomized, multicenter trial

Rajiv K. Pruthi

¹Comprehensive Hemophilia Center, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

,

Prasad Mathew

²Comprehensive Hemophilia Center University of New Mexico, Albuquerque, New Mexico, USA

,

Leonard A. Valentino

³Rush University Medical Center, Chicago, Illinois, USA

,

Michael J. Sumner

⁴Novo Nordisk, Princeton, New Jersey, USA

,

Stephanie Seremetis

⁴Novo Nordisk, Princeton, New Jersey, USA

,

Keith W. Hoots

⁵Gulf State Hemophilia Center, Houston, Texas, USA

,

the NovoSeven in Surgery Study Investigators

› Author Affiliations

Abstract

Summary

Bolus infusion (BI) recombinant factor VIIa (rFVIIa) administration is safe and effective in the surgical management of haemophilia patients with inhibitors but has not been compared directly with continuous infusion (CI). We conducted an open-label, randomized, multicenter trial comparing the efficacy and safety of rFVIIa administered by BI or CI for the surgical management of haemophilia A or B patients with inhibitors to FVIII or FIX. Safety was compared with that of a control group of noninhibitor patients receiving FVIII or FIX concentrates for major surgery. All inhibitor subjects received an initial bolus dose of 90 μg/kg rFVIIa and were then randomly assigned to BI (n=12) or CI (n=12). The BI group received 90 μg/kg rFVIIa every two hours (h) during surgery through day 5, then every four hours for days 6–10. The CI group received 50 μg/kg/h rFVIIa through day 5, then 25 mg/kg/h for days 6–10. The control group (n=12) received FVIII or FIX per institutional protocols. Twenty-two major surgeries included orthopedic procedures on the knee (n=13), hip (n=3), and abdominal/pelvis procedures (n=4). One patient with an autoimmune FVIII inhibitor randomized to the BI arm was excluded from efficacy analysis. Haemostatic efficacy of rFVIIa in each group was comparable: effective in 8/11 and 9/12 subjects in the BI and CI arms, respectively, and ineffective in three subjects in each arm. Serious adverse events were related to continued or increased bleeding. In conclusion, haemostatic efficacy and safety of BI and CI of rFVIIa are comparable for the surgical management of haemophilia subjects with inhibitors.

Keywords

Bolus - continuous - inhibitors - rFVIIa - surgery

Full Text

References

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