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01-05-2014 | Original Article

Tissue factor pathway inhibitor in activated prothrombin complex concentrates (aPCC) moderates the effectiveness of therapy in some severe hemophilia A patients with inhibitor

Authors: Kenichi Ogiwara, Keiji Nogami, Tomoko Matsumoto, Midori Shima

Published in: International Journal of Hematology | Issue 5/2014

Abstract

Some hemophilia A patients who have developed inhibitors are poorly responsive to activated prothrombin complex concentrates (aPCC) after daily dosage, but the mechanism(s) underlying this remain unknown. We examined two representative cases. In case 1, we found that changing to recombinant factor VIIa (rFVIIa) therapy was more effective, and the response to aPCC was restored within ~2 weeks. Tissue factor (TF)-triggered thrombin generation demonstrated a prolonged lag-time and decreased peak thrombin, and this impairment was focused on TF pathway inhibitor (TFPI). Plasma-free TFPI was elevated post-infusion of aPCC, while this was unaffected by rFVIIa. TFPI returned to normal range within 2–3 weeks. Plasmas obtained from patients with poor or good response to aPCC (aPCC-poor or aPCC-good), and good response to rFVIIa (FVIIa-good) demonstrated that free TFPI levels are increased in both aPCC groups, but not in FVIIa-good. TFPI levels pre- and post-infusion in aPCC-poor were significantly higher than those in aPCC-good. Addition of anti-TFPI antibody to the reaction samples demonstrated a greater increase of peak thrombin in aPCC-poor compared to aPCC-good, showing the higher TFPI activity in aPCC-poor. Free TFPI contained in aPCC corresponded to the increasing levels in plasma. In conclusion, TFPI in aPCC attenuated thrombin generation, and the reduced effectiveness of therapy in these circumstances appeared to be related to TFPI activity.

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Title: Tissue factor pathway inhibitor in activated prothrombin complex concentrates (aPCC) moderates the effectiveness of therapy in some severe hemophilia A patients with inhibitor
Authors: Kenichi Ogiwara
Keiji Nogami
Tomoko Matsumoto
Midori Shima
Publication date: 01-05-2014
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 5/2014
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-014-1572-4

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