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Additive effect of factor X on the structure and stability of activated factor VII-induced fibrin clot in hemophilic plasma with inhibitor

      Replacing deficient factor (F) VIII or FIX is the most common treatment strategy for congenital hemophilia; however, repeated infusions can promote the formation of FVIII or FIX inhibitors. Importantly, the appearance of these inhibitors significantly reduces the hemostatic effect of regular FVIII or FIX replacement [
      • Fischer K.
      • Lewandowski D.
      • Marijke van den Berg H.
      • Janssen M.P.
      Validity of assessing inhibitor development in haemophilia PUPs using registry data: the EUHASS project.
      ]. Recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrates (APCC) are used for hemostatic management in patients having hemophilia with inhibitors (PHwI). Additionally, the plasma-derived FVIIa (pdFVIIa) and FX mixture (FVIIa/FX; Byclot®, KM Biologics Co., Ltd., Kumamoto, Japan) comprising FVIIa and FX in a weight ratio of 1:10 that enhanced the hemostatic effect of FVIIa was approved in Japan for the episodic and prophylactic treatment of patients with PHwI. The recommended doses of FVIIa/FX for hemostatic control ranged from 60 to 120 μg/kg (FVIIa concentration), and the plasma concentration (Cmax) of FVIIa and FX can increase to 1.2–1.8 μg/mL and 17.3–29.7 μg/mL, respectively [
      • Shirahata A.
      • Fukutake K.
      • Takamatsu J.
      • Shima M.
      • Hanabusa H.
      • Mugishima H.
      • Amano K.
      • Takedani H.
      • Tamashima S.
      • Matsushita T.
      • Tawa A.
      • Tanaka I.
      • Higasa S.
      • Kosaka Y.
      • Fujii T.
      • Sakai M.
      • Migita M.
      • Kawakami K.
      • Ohashi Y.
      • Saito H.
      A phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics.
      ].

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