Continuous infusion in haemophilia: current practice in Europe

Abstract

Summary. Continuous infusion (CI) of factor VIII (FVIII) is an effective method for replacement therapy in haemophilia. Recently, concerns have been raised regarding association of CI with the development of inhibitors. The aim of this study was to gain information on the current practices in Europe regarding CI and the true inhibitor incidence after this mode of therapy. In a cross sectional study performed in 22 Comprehensive Care Centres (CCCs), we evaluated CI techniques, treatment protocols, efficacy, safety and complications of CI including inhibitors. Thirteen (59%) CCCs reported a total of 1079 CI treatments, given peri-operatively or for major bleeds, in 742 patients. Most centres used 'adjusted dose' CI aimed at median target FVIII level of 0.8 IU mL(-1). CI was haemostatically very effective with a low incidence of complications: median incidence of postoperative bleeding was 1.8%, six centres observed phlebitis in 2-11% of CI treatments. Only nine (1.2%) patients developed inhibitors (0.45% of 659 severe and 7.2% of 83 mild haemophilia patients). Additional analysis of inhibitor patients revealed several confounding factors (low number of prior FVIII exposure days, high steady-state factor levels during CI, high-risk genotype). In this unprecedentedly large cohort, CI treatment appears to be an effective and safe treatment that does not increase the risk of inhibitor development in patients with severe haemophilia. Thus, previous small case series reports suggesting that CI may increase inhibitors cannot be confirmed. Inhibitor risk in mild haemophilia could not be evaluated as the influence of other, potentially confounding, risk factors could not be excluded.

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

“…KI je posebej varen način nadomestnega zdravljenja, saj z njo vzdržujemo stalne aktivnosti FVIII / IX in znižamo celokupno porabo faktorja. S KI se izognemo nepotrebnim občasnim previsokim, tudi lahko nevarnim aktivnostim faktorja, poleg tega pa očistek strjevalnega faktorja v prvih dneh KI pomembno pade (51)(52)(53)(54)(55)(56)(57). V nasprotju z nekdanjim mnenjem pa danes izkušnje velikih centrov dokazujejo, da KI pri tež-ki in lahki obliki HA ne sproži pogostejše tvorbe inhibitorjev (55,58,59).…”

Genetic and Environmental Risk Factors for Factor VIII Inhibitor Development

“…This issue is of particular interest and concern for patients with milder forms of the disease not heavily exposed to the factor. In most studies, however, both continuous infusion and bolus injections have been used, and in some large centers significant numbers of patients have been treated with continuous infusion with no indication of an increased incidence of inhibitors [42]. Therefore, at least in patients with severe disease, there appears to be no evidence on which to base a recommendation that continuous infusion should be avoided and from a logical point of view the same should be true for those with a milder form.…”

Continuous Infusion of Coagulation Products in Hemophilia

“…Continuous infusion of factor VIII Continuous infusion using a variety of pdFVIII and rFVIII products has been introduced into common practise of hemophilia management worldwide, with 61% and 59% of comprehensive care centers employing CI in the US and Europe, respectively [19,20,24]. The Japanese guideline for hemophilia treatment suggest to use CI for major surgery [35,36].…”

“…Most recently Takedani [37], Rahmé et al [38], and Chevalier et al [39] reported on successful use of CI in 28, 20, and 72 total knee replacements, respectively. A prospective controlled study comparing CI and BI for major surgery using protocols that were similar regarding the surgical technique and postoperative target minimum levels demonstrated that efficacy and safety were better with CI than with BI in terms of minimum factor levels achieved, blood loss (as measured by a decrease in hemoglobin level), blood transfusion requirements, and bleeding complications ( [24]. The incidence of postoperative bleeding among the centers was only 1.8% (range 0-7.0%).…”

“…A prospective controlled study comparing CI and BI for major surgery using protocols that were similar regarding the surgical technique and postoperative target minimum levels demonstrated that efficacy and safety were better with CI than with BI in terms of minimum factor levels achieved, blood loss (as measured by a decrease in hemoglobin level), blood transfusion requirements, and bleeding complications ( [24]. Eight centers reported cost savings over traditional bolus therapy ranging from 15% to 36% [24]. Eight centers reported cost savings over traditional bolus therapy ranging from 15% to 36% [24].…”