Document Detail


The response to activated protein C after cardiopulmonary bypass: impact of factor V leiden.
MedLine Citation:
PMID:  15562039     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activated protein C (aPC) resistance is a recognized hypercoagulable phenotype that is associated with increased risk for thrombosis in multiple clinical settings. Factor V Leiden (FVL) represents a specific inherited cause of aPC resistance, but the perioperative thrombotic risk of FVL is unclear. In this investigation, we sought to quantify whether cardiopulmonary bypass produces alterations in aPC resistance in FVL carriers and noncarrier controls, testing the hypothesis that FVL is associated with a relatively hypercoagulable postoperative state. Two-hundred-five adult cardiac surgery patients were prospectively enrolled into a genetic registry whose purpose was to study the impact of genetic variables on clinical outcomes. For this study, 8 subjects heterozygous for FVL were identified (group L), as well as 2 control groups: group MC, matched controls, 18 matched subjects without FVL; and group UC, unmatched controls, 11 consecutive subjects without FVL. Plasma was sampled at the beginning of surgery, 10 min after protamine administration, and on postoperative day 1, and assayed for resistance to aPC (normal aPC ratio is >2.0). Both MC and UC groups exhibited normal aPC ratio at baseline (2.40 and 2.36, respectively), which increased significantly (to 2.76 and 2.75, P = 0.007 and 0.021, respectively) on postoperative day 1, indicating increased postoperative sensitivity to aPC. Conversely, group L subjects exhibited aPC resistance at baseline (aPC ratio 1.80), and did not change significantly postoperatively (P = 0.867). Patients without FVL therefore show laboratory evidence consistent with relative protection from postoperative thrombosis, whereas FVL carriers do not. These findings provide mechanistic support for previous speculations of increased postoperative thrombotic risk associated with FVL.
Authors:
Brian S Donahue
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  99     ISSN:  0003-2999     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-24     Completed Date:  2004-12-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1598-603, table of contents     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology, 504 Oxford House, Vanderbilt University, Nashville, TN 37232, USA. brian.donahue@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
Activated Protein C Resistance / genetics*,  physiopathology*
Cardiopulmonary Bypass*
DNA / genetics
Factor V / genetics*,  physiology*
Female
Heterozygote
Humans
Male
Middle Aged
Postoperative Complications / blood
Protein C / physiology
Thrombophilia / genetics,  physiopathology
Thrombosis / physiopathology
Treatment Outcome
Grant Support
ID/Acronym/Agency:
1-K23-HL04476/HL/NHLBI NIH HHS; 1-U01-HL65962/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Protein C; 0/factor V Leiden; 9001-24-5/Factor V; 9007-49-2/DNA

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


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