Factor (F)VIII/VIIa enhances global haemostatic function in the co‐presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor
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Media type:
E-Article
Title:
Factor (F)VIII/VIIa enhances global haemostatic function in the co‐presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor
Description:
<jats:title>Summary</jats:title><jats:p>Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor (<jats:styled-content style="fixed-case">PWHA</jats:styled-content>‐inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates (<jats:styled-content style="fixed-case">aPCC</jats:styled-content>) activated factor (F)<jats:styled-content style="fixed-case">VIII</jats:styled-content><jats:italic>in vitro,</jats:italic> and was mediated mainly by the activated <jats:styled-content style="fixed-case">FVII</jats:styled-content> (<jats:styled-content style="fixed-case">FVII</jats:styled-content>a) contained in <jats:styled-content style="fixed-case">aPCC</jats:styled-content>. We have extended those studies to assess global coagulation in whole blood from 18 <jats:styled-content style="fixed-case">PWHA</jats:styled-content>‐inh in the co‐presence of <jats:styled-content style="fixed-case">aPCC</jats:styled-content> and <jats:styled-content style="fixed-case">FVIII</jats:styled-content> using Ca<jats:sup>2+</jats:sup>‐triggered rotational thromboelastometry. The clot times (<jats:styled-content style="fixed-case">CT</jats:styled-content>s) in the presence of both <jats:styled-content style="fixed-case">aPCC</jats:styled-content> (0·05 iu/ml) and recombinant (r)<jats:styled-content style="fixed-case">FVIII</jats:styled-content> (1 iu/ml) <jats:italic>ex vivo</jats:italic> were shortened compared to the <jats:styled-content style="fixed-case">aPCC</jats:styled-content> alone (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0·01). These enhancing effects of <jats:styled-content style="fixed-case">rFVIII</jats:styled-content> were observed, irrespective of recognizing inhibitor epitopes; however, the clot formation time and ‘α’‐angle were not significantly different. In samples from 7 <jats:styled-content style="fixed-case">PWHA</jats:styled-content>‐inh post‐infusion of <jats:styled-content style="fixed-case">aPCC</jats:styled-content> (70‐80 iu/kg), only the <jats:styled-content style="fixed-case">CT</jats:styled-content>s were shortened in the presence of <jats:styled-content style="fixed-case">rFVIII</jats:styled-content><jats:italic>ex vivo</jats:italic> compared to its absence (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0·05), indicating that the enhanced activity centred on the initiation phase of coagulation. Furthermore, experiments in the co‐presence of <jats:styled-content style="fixed-case">rFVII</jats:styled-content>a and <jats:styled-content style="fixed-case">rFVIII</jats:styled-content> demonstrated that <jats:styled-content style="fixed-case">FVIII</jats:styled-content> accelerated only the <jats:styled-content style="fixed-case">CT</jats:styled-content>s. We concluded that <jats:styled-content style="fixed-case">FVIII</jats:styled-content>/<jats:styled-content style="fixed-case">FVII</jats:styled-content>a‐related coagulation mechanism enhanced global haemostatic function by the co‐presence of bypassing agents and FVIII in PWHA‐inh.</jats:p>