Haematologica
HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
QUICK SEARCH:   [advanced]


     

Published online 18 July 2008
Haematologica, Vol 93, Issue 9, 1351-1357 doi:10.3324/haematol.13039
Copyright © 2008 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dielis, A. W.J.H.
Right arrow Articles by Hamulyák, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dielis, A. W.J.H.
Right arrow Articles by Hamulyák, K.

Disorders of Hemostasis

Thrombomodulin-modified thrombin generation after in vivo recombinant factor VIII treatment in severe hemophilia A

Arne W.J.H. Dielis1, Wolfgang M.R. Balliël2, René van Oerle2, Wim T. Hermens3, Henri M.H. Spronk1, Hugo ten Cate1, Karly Hamulyák2

1 Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht
2 Department of Internal Medicine, Division of Haematology, University Hospital Maastricht, Maastricht
3 Delbia BV, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

Correspondence: Arne W.J.H. Dielis, MD, Maastricht University, PO Box 616, UNS50/Box 8, 6200 MD Maastricht, The Netherlands. E-mail:a.dielis{at}bioch.unimaas.nl

Background: Thrombin generation has been shown to reflect coagulation potential and factor VIII (FVIII) levels in patients with hemophilia A. We hypothesize that thrombin generation in the presence of thrombomodulin reflects plasma FVIII levels better.

Design and Methods: Plasma FVIII levels were determined chromogenically and thrombin generation was measured with and without thrombomodulin in 12 patients with severe hemophilia A. Blood was sampled at baseline and 15 min, 1, 3, 6, 24 and 48 hours after recombinant FVIII administration.

Results: FVIII administration restored the decreased baseline thrombin generation (reflected by endogenous thrombin potential, peak height, slope and time to peak). Lag time did not change. All thrombin generation parameters except time to peak returned to baseline within 48 hours, while plasma FVIII concentration was increased and time to peak shortened. Endogenous thrombin potential and peak height showed wide inter-individual variation, with strong intra-individual correlations. Addition of thrombomodulin to the assay shortened time to peak and decreased endogenous thrombin potential and peak height. The decrease in peak height was almost completely offset by FVIII administration. Multiple linear regression analysis revealed thrombomodulin-modified thrombin generation to be a moderately better predictor of plasma FVIII levels than thrombin generation in the absence of thrombomodulin (adjusted R2 0.79 vs. 0.71).

Conclusions: Addition of thrombomodulin has pronounced effects on all parameters of thrombin generation. This thrombomodulin-modified thrombin generation assay better reflects plasma FVIII levels than thrombin generation in the absence of thrombomodulin.

Key words: hemophilia A, thrombin generation, thrombomodulin, coagulation factor VIII.






HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
Copyright © 2008 by the Ferrata Storti Foundation.