Continuous infusion of B‐domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience

Abstract

This retrospective, open-label, non-comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto), B-domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as 'excellent' or 'good' in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non-haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non-serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild-to-moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well-tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well-tolerated regimen for patients with haemophilia A undergoing surgery.

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients

“…Unfortunately, in all these studies, only the FVIII loading dose was based on an individual PK-profile obtained several days before surgery. [30][31][32][33][34][35] Iterative perioperative FVIII dosing-adjustments after first loading dose could not be performed as there was no population PK model. The perioperative population PK model presented here will now make Bayesian adaptive dosing in this setting possible.…”

Continuous infusion during total joint arthroplasty in Japanese haemophilia A patients: comparison study among two recombinants and one plasma‐derived factor VIII

“…However, it was difficult to judge the continuous infusion rate and clearance. The initial infusion rate in previous studies [2,5,13–15] was from 1.8 to 6.0 IU kg −1 h −1 , and the average clearance of FVIII in previous studies [1,4,16] was from 2.65 to 3.89 mL kg −1 h −1 . In the above results, there are only three reports that described the clearance and infusion rate for a single product during some kinds of surgeries.…”

Successful double bypass in a patient with severe hemophilia A: a case report

“…In our case the patient was affected by severe hemophilia A and admitted to hospital for cardiac revascularization made by double bypass internal mammary artery -coronary artery. According to international guidelines and published studies, to control haemostasis the patient was treated during surgery and for thirteen postoperative days with continuous infusion of recombinant FVIII B-domain deleted [5,6]. A published review by Sharathkumar et al showed that inhibitor development [7] is a possible complication of continuous infusion of coagulation factor, but in our case the laboratory tests excluded this hypothesis.…”