Successful Use of Recombinant Factor IX Concentrate (Nonacog-alfa, Benefix®) in Two Patients with Severe Hemophilia B and Total Knee Replacement (TKR).
Authors: Gerhardt Andrea , Stahlschmidt Kristina , Ilg Ansgar , Scharf Rudiger E. , Zotz Rainer B. 
Published: April 2020

Abstract
Severe hemophilia is complicated by spontaneous joint bleedings, leading to severe secondary arthrosis. Hemophilic arthropathy with symptoms of incapacitating knee pain, not responding to medical treatment, associated with an impaired function is an indication for TKR. Compared to the general population, TKR in hemophiliacs is technically more demanding. A well-balanced hemostasis is the basic requirement for successful operative interventions in hemophilic patients. In the past decade, human plasma-derived factor IX concentrates (pdFIX) are used in the treatment and prevention of bleeding in patients with hemophilia B, but concerns remain regarding transmission of blood-borne pathogens, e.g. infectious prions causing new variant Creutzfeldt-Jakob disease, hepatitis A virus, and the transmission of parvovirus. This concern has stimulated intense efforts to develop a recombinant human factor (rFIX) product for use in persons with hemophilia B. Recombinant FIX is not exposed to human- or animal-derived proteins at any stage in manufacture or formulation, and therefore has an enhanced viral safety profile compared with current pdFIX products. It is structurally and functionally similar to pdFIX, although minor differences in the posttranslational sulfation and phosphorylation of rFIX have been associated with a lower in vivo recovery. Here in, we report on our experience with rFIX in 2 arthroplasties of knee joint arthropathies in 2 patients with severe hemophilia B. Indication for total knee replacement was arthropathy in stage III-V, flexion contracture, and axial malalignment. Mean hospitalization was 15.5 days (range 15–16 days). The patients received a non-constrained bicondylar TKA (LCS complete). Surgery was covered by appropriate rFIX replacement therapy with episodic bolus injections. A peri- and postoperative fIX level of 100% was required: an initial dose of rFIX (80 IU/kg/bw) was administered 15 min prior to surgery, followed by a dose of 30 to 40 IU/kg/bw immediately after surgery and 2 doses of 30 to 40 IU/kg/bw at 6 hours intervals postoperatively in both patients. In the first five days after surgery, 30 to 40 IU /kg/bw rFIX were administered every 8 hours (mean fIX trough level 95%; range 87% – 104%), followed by 30 to 40 IU/kg/bw every 12 hours for further 10 days mean fIX trough level 88%; range 60% – 99%). The postoperative blood loss in the drainage systems was 950 ml (patient 1) and 700 ml (patient 2), the preoperative and postoperative haemoglobin was 14.7g/dl/12.6g/dl (patient 1) and 14.2g/dl/11.5 g/dl (patient 2). Transfusion of red blood cells was not required in any of the patients. Postoperative thromboembolic prophylaxis with low molecular weight heparin (4000 IE/day) was performed. We observed good short-term results after a mean follow-up interval of 46.5 months (range 53 – 40 months) with no peri- and postoperative thromboembolic or bleeding complications and no infections. The extension deficit improved from 29.3° preoperatively to 3° postoperatively in average with no signs of instability. In conclusion, TKR results in improvement in quality of life because of pain-relief and increase of motility and function in all patients. Recombinant FIX appears to be an effective and safe therapeutic treatment option for prophylaxis of bleeding episodes in TKR in patients with severe hemophilia B.