title: Effects of nucleotides and nucleosides on coagulation.
abstract: 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.affiliation: Copenhagen Muscle Research Centre, Rigshospitalet, Denmark.
authors.forename: Laurids T
authors.initials: LT
authors.lastname: Bune
authors.forename: Pia
authors.initials: P
authors.lastname: Thaning
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Louise
authors.initials: L
authors.lastname: Bochsen
authors.forename: Jaya B
authors.initials: JB
authors.lastname: Rosenmeier
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D009705:Nucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D009711:Nucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine
chemical_list: D009705:Nucleosides; D009711:Nucleotides; D009569:Nitric Oxide