Experience with Optivate®, a new high purity concentrate of factor VIII with von Willebrand factor, in patients undergoing surgery

Abstract

The efficacy and safety of Optivate(®) was assessed in 23 surgical operations, orthopaedic (12) including 5 revision arthroplasties, ophthalmic (1), ENT (1), dental (6), liver biopsy (2), and removal of portacath (1) on 15 teenagers and adults with severe haemophilia A. The preoperative dose was calculated to raise the FVIII concentration to 100 IU dL(-1). Subsequent doses were targeted to maintain at least 50 IU dL(-1). There were 11 major and 12 minor operations categorized as receiving intensive replacement therapy for ≥ 5 days or < 5 days respectively. The median preoperative dose was 50.4 (range 18.2-88.2) IU kg(-1). The median incremental recovery based on this first dose in 10 procedures (5 patients) was 2.9 (range 2.4-3.4 IU dL(-1) ) per IU kg(-1). The daily doses decreased during the first 4 days of the study. The patients in this study received 173 infusions in total. Outcome was 'good' or 'excellent' for 19 (83%) of 23 operations, 'uncertain' in three procedures because an antifibrinolytic agent was used as well and for one procedure outcome was not assessed. Tolerance was good. There were no excessive bleeds, no inhibitors and no virus transmissions.

Thrombotic adverse events to coagulation factor concentrates for treatment of patients with haemophilia and von Willebrand disease: a systematic review of prospective studies

“…Types and brands of factor concentrates administered in the selected studies are shown in Table 1. Forty‐five studies [20–64] reported patients with HA receiving FVIII concentrates (Table 2), 15 studies [65–79] patients with HB treated with FIX concentrates (Table 3) and 11 studies [80–90] VWD patients treated with VWF containing products (Table 4). Owing to the peculiar pathophysiologic situation, six studies [91–96] reporting haemophilia patients who had central venous access devices (CVAD) in order to facilitate long‐term regular concentrate administration (prophylaxis, immune tolerance induction) were analyzed separately (Table 5).…”

“…Five studies [32,41,63,73,75] reported only treatment of bleeding episodes (three in HA, two HB), whereas in most cases patients on regular prophylaxis (17 studies; 16 HA, 1 VWD) or undergoing surgical procedures (11 studies; 4 HA, 3 HB, 4 VWD) or both (24 studies; 15 HA, 7 HB, 2 VWD) were also evaluated. Twelve studies [39,48,53,57,64,65,69,71,83,84,86,90] reported only surgical interventions (6 HA, 2 HB, 4 VWD), three of these studies (2 HA, 1 HB) focusing on factor administration by continuous infusion (CI) [39,53,71]. Patients with HA and inhibitors receiving FVIII concentrates for immune tolerance induction were also included in three studies [34,38,47], whereas indications of treatments were not specified in two (one HA, one HB) [20,70].…”

Pharmacokinetic profile of Optivate® (high‐purity factor VIII/von Willebrand factor concentrate) in treating von Willebrand disease

“…Overall Optivate was well tolerated. There have been no reports of inhibitor development to FVIII and/or VWF with Optivate in this study or any of the other clinical studies [2,[6][7][8][9] or from postmarketing experience to date.…”

“…Optivate is licensed in several countries worldwide for the treatment of Haemophilia A in both adults and children [6][7][8][9]. This letter reviews data from a BPL sponsored single centre, randomized pharmacokinetic (PK) study comparing Optivate and Haemate P (also known as Humate P) in VWD patients.…”

“…Therefore, maintaining lower postinfusion FVIII levels could possibly lower the risk of thrombosis. To date, there have been no adverse reactions with a thrombotic aetiology from either formal clinical trials or reporting of spontaneous adverse drug reactions with Optivate [2,[6][7][8][9]. In addition, thrombogenicity data gathered from a separate Optivate study in 11 VWD patients (unpublished data) concluded there was no clinical evidence of thrombosis.…”