Document Detail


Effects of nucleotides and nucleosides on coagulation.
MedLine Citation:
PMID:  20389237     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion of adenosine, ADP, ATP, UTP or nitric oxide until mean arterial pressure was reduced to approximately 40% of baseline simulating sepsis-induced hypotension. The effect of the infusions on the haemostatic system was evaluated by TEG, and endothelial release of tissue plasminogen activator and plasminogen activator inhibitor-1 was measured. In contrast to the other infused substrates, ADP caused a reduction in maximum amplitude (71.4 to 64.2; P < 0.05), and reduced the angle, representing the thrombus formation (75.6 to 66.4; P < 0.05), indicating hypocoagulation. Despite increases in t-PA release (2.1 to 2.7 ng/ml; P < 0.05) and reductions in plasminogen activator inhibitor (33.9 +/- 10.9-17.8 +/- 4.4 ng/ml; P < 0.05) no increased fibrinolysis was found when whole blood was evaluated by TEG. Circulating ADP induces hypocoagulation without signs of increased fibrinolysis as evaluated by TEG. The potential clinical significance of these findings should be investigated further because ADP discharged systemically may possibly contribute to the coagulopathy observed in severe sepsis.
Authors:
Laurids T Bune; Pia Thaning; Pär I Johansson; Louise Bochsen; Jaya B Rosenmeier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis     Volume:  21     ISSN:  1473-5733     ISO Abbreviation:  Blood Coagul. Fibrinolysis     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9102551     Medline TA:  Blood Coagul Fibrinolysis     Country:  England    
Other Details:
Languages:  eng     Pagination:  436-41     Citation Subset:  IM    
Affiliation:
Copenhagen Muscle Research Centre, Rigshospitalet, Denmark.
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