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Blood Res. 2013 Dec;48(4):282-6. doi: 10.5045/br.2013.48.4.282. Epub 2013 Dec 24.

Sequential therapy with activated prothrombin complex concentrates and recombinant activated factor VII to treat unresponsive bleeding in patients with hemophilia and inhibitors: a single center experience.

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  • 1Department of Pediatrics, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Korea.



Currently, the greatest challenge in hemophilia treatment is managing hemophilia patients with inhibitors. The two main bypassing agents that are used to treat hemophilia patients with inhibitors are activated prothrombin complex concentrates (APCC) and recombinant factor VIIa (rFVIIa). Hemophilia patients with inhibitors can develop bleeding episodes, that are refractory to monotherapy with either APCC or rFVIIa and thus are often difficult to manage.


This report describes a retrospective chart review of four hospitalized patients with severe hemophilia and inhibitors who were treated with sequential therapy of APCC and rFVIIa for refractory bleeding. Sequential therapy was defined as the administration of both rFVIIa and APCC within 12 h.


In 5 episodes experienced by 4 patients with inhibitors, bleeding was not controlled by single bypass treatment, but it was controlled when two agents were sequentially administered. Sequential therapy was administered by alternating one APCC dose to 1 to 2 rFVIIa doses, with dosing intervals ranging from 3 to 6 h. All bleeding episodes were controlled within 12 to 24 h. Sequential therapy was discontinued after 2 to 5 days. No adverse clinical events, such as thrombosis, were observed.


Sequential therapy with APCC and rFVIIa was efficacious without adverse events; however, attention on thrombosis is needed. In addition, a prospective clinical trial is needed to provide further evidence for this treatment.


Hemophilia; Inhibitor

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