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Thrombin generation in haemophilia A patients with factor VIII inhibitors after infusion of recombinant factor VIIa.
MedLine Citation:
PMID:  19490067     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Development of factor VIII inhibitors is a serious complication in haemophilia A patients. Recombinant factor VIIa (rVIIa) is clinically effective, but its effects on haemostatic system need still to be fully elucidated. MATERIAL AND METHODS: In an open controlled study, we measured thrombin generation (peak thrombin) in venous blood and prothrombin fragment F1 + 2 (F1 + 2) and D-dimer in venous and in shed blood in five haemophilia A patients with inhibitors before and after rVIIa infusion. A total of five healthy individuals who did not receive rVIIa served as controls. RESULTS: At baseline, patients had lower mean (min-max) peak thrombin levels than controls [0.12 (0.0-0.6) vs. 186.9 (116.0-254.4) nM, P = 0.001]. After infusion, peak thrombin levels increased in average to 40.7 (28.3-51.6) nM, which translates into 80.2% (95% CI 65.4-88.6%) lower levels compared to that of controls. Mean (min-max) F1 + 2 levels in venous blood did not differ significantly between patients and controls [160.7 (89.8-331.3) vs. 160.8 (104.4-242.3) pmol L(-1)], but increased in average (min-max) by 39.4% (14.1-58.5%) after infusion. In blood emerging from incisions made to determine the bleeding (shed blood), F1 + 2 levels were lower in patients than controls [1383.3 (906.4-2044.6) vs. 2981.7 (1610.0-4539.6) pmol L(-1); P = 0.04], but were not affected by rVIIa; D-dimer levels were significantly higher in haemophiliacs than in controls and remained unchanged after infusion. CONCLUSIONS: Haemophilia A patients with factor VIII inhibitors have low thrombin generation. After rVIIa, the extent of coagulation activation as measured by levels of F1 + 2 is increased, but thrombin generation is restored to only 20%. Peak thrombin levels could reflect the effects of rVIIa on coagulation mechanisms, and their relevance with regard to the clinical coagulation defect of haemophilia A patients with factor VIII inhibitors might be evaluated.
Authors:
S Eichinger; B Lubsczyk; M Kollars; L Traby; K Zwiauer; A Gleiss; P Quehenberger; P A Kyrle
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Publication Detail:
Type:  Journal Article     Date:  2009-05-26
Journal Detail:
Title:  European journal of clinical investigation     Volume:  39     ISSN:  1365-2362     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  England    
Other Details:
Languages:  eng     Pagination:  707-13     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria. sabine.eichinger@meduniwien.ac.at
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