Document Detail


Optimizing management of hirudin anticoagulation.
MedLine Citation:
PMID:  15804161     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accurate anticoagulation monitoring, critical during cardiac surgery (CS), is especially important for novel therapeutics such as hirudins, for which there are no known antidotes. The activated clotting time (ACT), which is standard for heparin monitoring, has been reported to be insufficiently sensitive to high levels of hirudins. A simple, accurate, and sensitive assay is needed to monitor hirudins at the levels required for CS. During the REPLACE/II clinical trials, the HEMOCHRON Jr. Signature ACT+ was used to monitor Angiomax during percutaneous cardiac intervention (PCI) procedures and was observed to lose sensitivity at bivalirudin concentrations greater than 8-10 microg/mL. A new assay, the ACTT, was developed to increase the linear sensitivity of the ACT+ over the range of 15-30 microg/mL bivalirudin to extend the clinical utility of the assay to CS levels. Both in vitro and ex vivo studies were performed using the ACTT and ACT+. In vitro ACT+ and ACTT clotting times, identical for bivalirudin levels up to approximately 5 microg/mL, diverged from each other near 10 microg/mL. The ACTT showed excellent linearity to bivalirudin at concentrations up to 30 microg/ mL. Reproducibility was also superior with coefficients of variation <15% across 13 donors at clotting times <760 seconds. The ACTT was evaluated for monitoring bivalirudin during PCI in 67 patients. The ex vivo comparison of ACTT to ACT+ <340 seconds, showed a slope near 1.0 and an average difference between the tests of 5%. At higher clotting times this slope increased to near 3.0, with an average difference between tests of 20%. These data suggest that the ACTT displays increased sensitivity to high levels of bivalirudin.
Authors:
Megan A Measday; Marcia L Zucker; Chi-Miau Pan; Frank M LaDuca
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of extra-corporeal technology     Volume:  37     ISSN:  0022-1058     ISO Abbreviation:  J Extra Corpor Technol     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-04-04     Completed Date:  2005-06-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0267637     Medline TA:  J Extra Corpor Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-70     Citation Subset:  T    
Affiliation:
International Technidyne Corporation, Edison, New Jersey 07039, USA.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Transluminal, Percutaneous Coronary
Blood Coagulation
Blood Coagulation Tests*
Cardiopulmonary Bypass / methods*
Drug Monitoring*
Fibrinolytic Agents / pharmacology*
Hirudin Therapy
Hirudins / analogs & derivatives*,  pharmacology*
Humans
Peptide Fragments / pharmacology*
Point-of-Care Systems
Recombinant Proteins / pharmacology*
Thrombin Time
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Hirudins; 0/Peptide Fragments; 0/Recombinant Proteins; 128270-60-0/bivalirudin

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


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