Factor IX replacement to cover total knee replacement surgery in haemophilia B: a single‐centre experience, 2000–2010

Abstract

Total knee replacement (TKR) is a well recognized treatment for haemophilic arthropathy. Successful haemostasis can be achieved by bolus doses or continuous infusion (CI) using either recombinant (r) or plasma-derived (pd) factor IX (FIX). We retrospectively analysed our experience of factor replacement to cover TKR in haemophilia B patients and explored factors related to FIX use during surgery. Between 2000 and 2010, 13 primary TKRs were performed in 11 haemophilia B patients. Operations were performed by the same surgeon using standard techniques. Median age was 58 years (42-79). An adjusted CI protocol was used for 5 days followed by bolus doses. FIX:C was maintained at 100 IU dL(-1) in the immediate postoperative period. There was no excess haemorrhage. There was no evidence of thrombosis or infection. All patients received mechanical thromboprophylaxis and only one chemical. CI was used in seven cases. Ten patients received pdFIX. Median hospital stay was 14 days (8-17). Median factor usage was 999 IU kg(-1) (768-1248). During CI, factor consumption was 695 IU kg(-1), 691 IU kg(-1) and 495 IU kg(-1) for BeneFix®, Replenine® and Haemonine, respectively. Clearance of both pdFIX and rFIX reduced during CI. All operations were uncomplicated. The decreased clearance in the CI setting reduced the amount of FIX required to maintain a therapeutic level. This reduction was greater with pdFIX and may be related to pharmacokinetic differences between pdFIX and rFIX. Given the excellent safety profile of the pdFIX products, CI of FIX and particularly pdFIX is safe, efficacious and convenient.

Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open‐label, uncontrolled, multicentre, phase III study

“…To some extent, two key concerns continue to present challenges to the current factor replacement approaches -treatment-related thrombogenicity and formation of inhibitor antibodies against FIX. Thrombosis has been reported following use of plasma derived or rFIX replacement by continuous infusion [10,21,22]. Neither the current nor the previous BAX326 study [5] showed any indication of thrombotic events.…”

Evidence of clinically significant extravascular stores of factor IX

“…[4] Furthermore,, in hemophilia B patients that receive continuous infusion of FIX for surgery, the amount of FIX required to maintain a level of 100% decreases with time—as though one were saturating binding sites. [5] These data suggest the existence of a significant extravascular FIX compartment.…”

Research in haemophilia B – approaching the request for high evidence levels in a rare disease

“…Information on 31 selected JA concerning 35 studies on HB and/or FIX is provided in Table . Overall 21 published studies (60.0%) were related to FIX, of which 17 (48.6%) were on safety, efficacy and/or pharmacokinetics of different FIX products , two studies on dosing , one on allergic reactions and one on use of FIX worldwide . HB was the focus of seven studies, of which three studies compared features of HA or FVII deficiency to HB, two studies on correlation between genotype and phenotype of HB , one registry on incidence of inhibitors, allergic and anaphylactic reactions and one study on the global prevalence of HB .…”