Continuous factor VIII infusion therapy in patients with haemophilia A undergoing surgical procedures with plasma‐derived or recombinant factor VIII concentrates

Abstract

We describe the experience of a single medical centre with continuous factor VIII (FVIII) infusion therapy in a cohort of patients undergoing elective surgery. Twenty-eight patients had a total of 45 procedures. Intraoperative haemostasis was considered excellent in all 45 cases. FVIII levels were maintained between 46% and 191% of normal (median, 103%) for 2-7 days. Bleeding occurred after five procedures (11%) at times when factor VIII levels were within haemostatic range. No patient required reoperation to control bleeding. There were no cases of sepsis related to continuous infusion of factor VIII. We conclude that continuous infusion: (1) is a safe and effective means of replacement therapy in patients with haemophilia undergoing surgery; (2) provides easier monitoring and more constant coagulation factor levels; and (3) has the potential to decrease the cost of replacement therapy by reducing overall usage of product.

Continuous infusion of coagulation factors: current opinion

“…Bidlingmaier et al [34 ], in a prospective open-labeled nonrandomized study with 43 continuous infusion treatments for surgery in children with hemophilia, proved continuous infusion to be a safe and effective method of perioperative care in children with reduced factor requirements. The mean total FVIII consumption for minor, moderate and major surgery, however, was still quite high compared with other studies (Table 1) [2, 13,15]. The authors feel that the high FVIII targets may not be necessary in all patients [34 ].…”

“…The most There are variations in continuous infusion protocols currently used and they concern different steady state factor levels targeted, resulting in different dosage and total factor demands. These variations may be explained by the lack of evidence-based information on the hemostatic minimum for specific clinical situations, or anecdotal bleeding complications occurring even at factor levels higher than those empirically considered as hemostatically sufficient [15,34 ]. Some centers seeking cost-effectiveness use low-dose continuous infusion protocols [14,56], however, other centers emphasize safety rather than costeffectiveness and use a 'high fixed dose continuous infusion' (4.0-5.0 IU/kg/h), instead of 'adjusted dose continuous infusion' [2] and target the steady state levels around 1.0 IU/ml [15,16 ,34 ].…”

“…An additional significant advantage of continuous infusion is its factor saving potential owing to the avoidance of unnecessary high peak levels that inevitably accompany bolus injection treatment [8][9][10]. Despite the existence of simple guidelines for continuous infusion [2, 6 ,10], in practice, the methods still vary widely and this is expressed mainly by different steady state factor levels targeted, resulting obviously in different dosing regimes (fixed rate, adjusted dose continuous infusion) and total factor requirements [10][11][12][13][14][15]16 ].…”

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 of Coagulation Products in Hemophilia

“…A good stability and low volume of concentrates allow to employ comfortable portable mini-pumps [18] with the exchange of infusion bags with concentrated products at intervals of 1-3 days (and longer), making this treatment convenient [1]. Nevertheless, in the USA and Canada, 59% and 80% of hemophilia centers employing the CI method, respectively, further dilute the concentrates with 60-500 mL of normal saline, and only 41% of US centers use the products up to 24 h after reconstitution [5,19,20].…”