Tissue factor pathway inhibitor in activated prothrombin complex concentrates (aPCC) moderates the effectiveness of therapy in some severe hemophilia A ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-04-01

AUTHORS

Kenichi Ogiwara, Keiji Nogami, Tomoko Matsumoto, Midori Shima

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. More... »

PAGES

577-587

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-014-1572-4

DOI

http://dx.doi.org/10.1007/s12185-014-1572-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008380679

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24687919


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