Document Detail


In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris.
MedLine Citation:
PMID:  10978264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1+2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving either recombinant hirudin (31 patients) or heparin (36 patients). Blood samples were obtained at baseline (before any treatment), after 3 to 5 days of study drug infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drug discontinuation were significantly lower than at baseline (P:=0.0014), whereas they had not changed in the patients receiving heparin; at this time point, the difference between patients receiving hirudin and those receiving heparin was statistically significant (P:=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were similarly persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion were significantly lower than at baseline in both treatment groups (P:=0. 0005 for hirudin and P:=0.042 for heparin) and remained lower after 1 month (P:=0.0001 for both hirudin and heparin). The fibrinopeptide A plasma levels were not different between patients treated with hirudin versus heparin at baseline, at the end of infusion, and after 1 month. Thus, in patients with unstable angina, in vivo thrombin generation and activity are reduced during intravenous infusion of recombinant hirudin. However, the inhibition of thrombin generation is not sustained, and after 1 month, the majority of patients have biochemical signs of increased thrombin generation.
Authors:
P A Merlini; D Ardissino; R D Rosenberg; E Colombi; P Agricola; L Oltrona; F Ottani; M Galvani; K A Bauer; B Bottasso; F Bertocchi; P M Mannucci
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  20     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-12     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2162-6     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Ospedale Niguarda Ca' Granda, Milan, Italy. ARDIS001@planet.it
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MeSH Terms
Descriptor/Qualifier:
Aged
Angina Pectoris / metabolism*
Angina, Unstable / metabolism*
Female
Heparin / pharmacology*
Hirudins / pharmacology*
Humans
Infusions, Intravenous
Male
Middle Aged
Recombinant Proteins / pharmacology
Thrombin / metabolism*
Chemical
Reg. No./Substance:
0/Hirudins; 0/Recombinant Proteins; 9005-49-6/Heparin; EC 3.4.21.5/Thrombin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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