No inhibitor development after continuous infusion of factor concentrates in subjects with bleeding disorders undergoing surgery: a prospective study

Abstract

Inhibitor development against von Willebrand factor, factor VIII or factor IX is one of the most severe complications of treating patients with von Willebrand's disease (VWD), haemophilia A or haemophilia B respectively. Continuous infusion of factor concentrate has been implicated as a risk factor for inhibitor development. This prospective study investigated inhibitor development after continuous infusion of factor concentrate for surgical procedures in subjects with VWD or a severe form of haemophilia (factor activity <1%). Observations were made on the occurrence of inhibitor formation, adverse events and virus seroconversions. Main inclusion criteria comprised a negative history of inhibitors to replacement factor concentrate, ≥ 50 exposure days to factor concentrate and anticipated surgery requiring replacement factor coverage for ≥ 3 days. Therapy began with a bolus dose of 30-50 IU kg(-1) body weight of factor concentrate followed by continuous infusion with 3-4 IU kg(-1) h(-1) . Continuous infusion dose of factor concentrate was adjusted based on factor levels measured at least once daily. In 46 subjects included in the study to date, no inhibitors have been identified at discharge or follow-up (3-4 weeks after surgery), and no thrombotic events or postoperative wound infections occurred. All subjects underwent surgery without major blood loss, and hemostatic efficacy was generally rated 'excellent'. The results of the current study are promising, although the number of subjects is too small to make a definitive statement about the incidence of inhibitor development during continuous infusion of factor concentrate. Therefore, this study will be continued.

Continuous infusion of recombinant factor VIII formulated with sucrose in surgery: Non‐interventional, observational study in patients with severe haemophilia A

“…At the end of the study, none of the patients had developed inhibitors to FVIII; yet, all had over 150 EDs to FVIII and no documented history of inhibitors at enrolment. Similarly, other studies have reported no de novo inhibitors for FVIII‐experienced patients who received rFVIII as CI during surgery , and a review of summary data for FVIII in over 70 surgeries in previously treated patients found no reports of inhibitor development . One limitation of this study is that inhibitor tests from some patients are missing, as they might have been considered low‐risk patients and therefore not been more often tested in usual practice.…”

Surgery in patients with von Willebrand disease

“…Factor replacement can be administered via continuous infusion or intravenous bolus infusion [13]. In this study, intravenous bolus infusion was the route of administration in all operations when factor concentrate was used.…”

Risks and challenges of orthopaedic invasive interventions in haemo -philia in a low-resource country

“…The most challenging complication was the development of inhibitors in PwH preoperatively not considered for this situation, imposing the change of replacement therapy to a prohibitive therapy, difficult to access because of the costs (22). It seemed not to be connected with the factor concentrate or the modality of factor concentrate administration (bolus vs. infusion, plasma derived vs recombinant) (23). It is difficult to answer the question regarding the responsible factor or condition for inhibitor formation.…”