Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94‐9027) for haemophilia A

Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94-9027) for haemophilia A - Gu - 2014 - Haemophilia - Wiley Online Library Skip to Main Content Log in / Register Log In E-Mail Address Password Forgotten Password?

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Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94-9027) for haemophilia AJ-M. Gu1,*, P. Ramsey1, V. Evans1, L. Tang2, H. Apeler2, L. Leong1, J. E. Murphy2, V. Laux1 andT. Myles1Article first published online: 29 JAN 2014

DOI: 10.1111/hae.12374

© 2014 John Wiley & Sons Ltd

Issue

HaemophiliaVolume 20, Issue 4, pages 593–600, July 2014

Additional Information

How to CiteGu, J.-M., Ramsey, P., Evans, V., Tang, L., Apeler, H., Leong, L., Murphy, J. E., Laux, V. and Myles, T. (2014), Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94-9027) for haemophilia A. Haemophilia, 20: 593–600. doi: 10.1111/hae.12374

Author Information1

Hematology Research, US Innovation Center, Bayer HealthCare Pharmaceuticals, San Francisco, CA, USA

2

Biological Research, US Innovation Center, Bayer HealthCare Pharmaceuticals, San Francisco, CA, USA

* Correspondence: Jian-Ming Gu, Bayer HealthCare, LLC, 455 Mission Bay Blvd South, San Francisco, CA 94158, USA.
Tel.: +1 415 437 5901; fax: +1 415 437 5968;
e-mail: jian-ming.gu@bayer.com

Publication HistoryIssue published online: 20 JUN 2014Article first published online: 29 JAN 2014Manuscript Accepted: 18 DEC 2013Funded byBayer HealthCare SEARCH Search Scope All contentPublication titlesIn this journalIn this issue Search String Advanced >Saved Searches > SEARCH BY CITATION Volume: Issue: Page: ARTICLE TOOLSGet PDF (488K)Save to My ProfileE-mail Link to this ArticleExport Citation for this ArticleGet Citation AlertsRequest Permissions AbstractArticleReferencesCited By View Full Article (HTML) Enhanced Article (HTML) Get PDF (488K) Keywords:aPTT assays;clotting time;coagulation tests;factor VIII;haemophilia;PEGylationSummary

Patients with haemophilia (PWH) are usually monitored by the one-stage activated partial thromboplastin time (aPTT) factor VIII (FVIII) assay. Different aPTT activators may affect clotting time (CT) and FVIII:C levels in patients treated with PEGylated FVIII. To evaluate the characteristics of PEGylated FVIII (BAY 94-9027) in various aPTT clotting assays, and to identify suitable aPTT reagents for monitoring BAY 94-9027 during the treatment of PWH, BAY 94-9027 and World Health Organization (WHO) 8th FVIII standards (WHO-8) were spiked into pooled and individual severe haemophilia A plasma at 1.0, 0.25 and 0.05 IU mL-1. Five commercial aPTT reagents widely used in clinical laboratories were compared and evaluated for BAY 94-9027 activity in plasma from PWH. BAY 94-9027 and WHO-8 bestowed similar CT and excellent precision when ellagic acid (SynthAFax, Dade Actin, and Cephascreen) aPTT reagents were used. In contrast, BAY 94-9027 showed significantly prolonged CT and poor precision compared with WHO-8 using silica aPTT reagents (APTT-SP and STA PTT 5). Furthermore, free 60-kDa polyethylene glycol (PEG), used for the conjugation of FVIII, showed a dose-dependent prolongation of CT in the APTT-SP assay. There was no effect on the SynthAFax-APTT, prothrombin time, or FXIa-initiated thrombin generation assay, demonstrating that the PEG moiety on FVIII has no general effect on the coagulation cascade. In summary, ellagic aPTT reagents (SynthAFax, Dade Actin, and Cephascreen) are most suitable for evaluating potency of BAY 94-9027 and should be the preferred aPTT reagents used in clinical laboratories for monitoring FVIII activity after infusion of BAY 94-9027 to PWH.

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