Intermittent injections vs. continuous infusion of Factor VIII in haemophilia patients undergoing major surgery

Abstract

Summary. Continuous infusion (CI) of factor VIII (FVIII) has been proved to be a safe alternative to intermittent bolus injections (BI) in haemophilia A. Most reports on CI suggest a considerable saving in FVIII compared with historical controls treated with BI, but some recent reports failed to demonstrate such an effect. The present study prospectively compared safety, efficacy and factor requirements in 43 major surgical procedures performed in severe haemophilia A patients who were treated with either BI (18 operations) or CI (25 operations). The aim was to maintain factor VIII levels above the same minimum levels. Improved safety of CI over BI was observed, despite a bias in favour of the BI group (all underwent unilateral operations, compared with 24% of the CI group who underwent bilateral operations). Higher nadir levels were found in the CI group (0´44^0´06 vs. 0´31^0´09 IU/ml; P , 0´01) with a lower incidence of dangerous drops below 0´3 IU/ml (8% vs. 44% of patients respectively; P , 0´01), and a lower drop in haemoglobin (Hb) (1´56^1´21 vs. 3´01^2´13 g/dl; P , 0´05) and blood transfusion requirements (12% vs. 39%; P , 0´01). Major bleeding complications developed in three out of 18 patients (17%) in the BI group and none of the CI group (P 0´06). The FVIII dosage was lower by 36% in the CI group (467^104 vs. 733^126 IU/kg; P , 0´01). Had the trough factor levels been maintained at the target levels, a greater difference of 72% would probably have been observed.

Continuous infusion of coagulation factors: current opinion

“…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 ].…”

Stability of full‐length recombinant FVIII formulated with sucrose during continuous infusion using a mini‐pump infusion device

“…In this context, plasma levels of D-dimer (DD), a marker of endogenous fibrinolysis, may have clinical and prognostic significance with higher DD values being associated with a more advanced stage of disease and shortened survival [2][3][4][5]. Given the involvement of the hemostatic system in tumor progression, the therapeutic use of anticoagulants could have a positive impact on the survival of cancer patients and several studies have indeed suggested that low-molecular weight heparin (LMWH) might prolong survival in cancer patients with [6-8] and without venous thromboembolism (VTE) [9][10][11].…”

“…This review compiled the data from a number of studies that compared bolus and continuous infusion therapies. A notable prospective study by Batarova and Martinowitz [3] compared the safety, efficacy, and factor requirements in 43 major surgical procedures performed in severe hemophilia patients with either bolus injections or continuous infusion. This study showed that continuous infusion of FVIII resulted in significantly higher nadir FVIII levels (P < 0.01), a significantly lower drop in hemoglobin levels (P < 0.05), significantly lower transfusion requirements (P < 0.01), and a significantly lower FVIII dosage (P < 0.01) compared with bolus injection.…”

Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion

“…In fact, availability of FVIII product at the end of phase 1 of the study (week 13) was greater than at baseline. This finding may be explained by a saturation of FVIII binding sites 37,38 due to low-level FVIII protein production due to the vector.…”