The use of continuous infusion of factor concentrates in the treatment of hemophilia

Abstract

Bolus infusion of clotting factor concentrates remains the most common approach to the treatment or prevention of bleeding in patients with hemophilia. Although successful use of continuous infusion of such concentrates has been reported by several groups, this alternative treatment method has not achieved widespread popularity. We report here our experience in one hemophilia center with the use of continuous infusion of factor VIII and factor IX concentrates in 13 patients, 11 with hemophilia A, and 2 with hemophilia B. All patients were treated successfully for bleeding episodes (e.g., hemarthroses, intracranial, or gastrointestinal bleeding) or for surgical procedures (appendectomy, thoracotomy, etc.). Three patients with low titer factor VIII inhibitors were treated successfully with constant infusion therapy, requiring a mean dose of factor VIII concentrate 2.3 fold (8.20 u/kg/h) higher than that of the patients without inhibitors (3.63 u/kg/h) to maintain a circulating plasma level of factor VIII of 1 u/ml. The use of constant infusion of clotting factor concentrates is safe, efficacious, and more convenient than bolus therapy of factor concentrates and should be considered for hospitalized hemophilia patients requiring replacement therapy.

Evaluation of recombinant factor VIII (Kogenate®) stability for continuous infusion using a minipump infusion device

“…This mechanism of FVIII delivery has been used to provide haemostasis for surgery [4, 5], primary or secondary prophylaxis [6–8], treatment for severe bleeding episodes [5, 9–11] and induction of tolerance in haemophiliac individuals having factor VIII allo‐antibodies [12–14]. Continuous infusion is superior to sequential bolus injections, in that considerably less FVIII is utilized, resulting in reduced cost [15, 16]. Furthermore, continuous infusion results in stable levels of circulating rFVIII activity, in contrast to the peaks and troughs observed with intermittent bolus infusions or injections [17].…”

Efficacy and safety of continuous infusion of Mononine® during five surgical procedures in three hemophilic patients

“…In 1989, Bona et al [3] reported the continuous infusion of Konine (Cutter Pharmaceuticals, Berkeley, CA) in two moderate haemophilia B patients without inhibitors: one of them had been admitted for synovectomy, the other for hemorrhagic syndrome. Stigendal et al [25] reported the case of a hemophilia B patient who underwent a total hip replacement with a continuous infusion of Immunine (Immuno AG, Vienna, Austria).…”

“…Further studies using immunopurified or recombinant factor VIII confirmed the advantages of this method compared to bolus injections [3][4][5][6][7][8][9][10][11].…”

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).…”