Effects of nucleotides and nucleosides on coagulation

Area of Science:

• Cardiovascular Physiology
• Hemostasis and Thrombosis
• Sepsis Pathophysiology

Background:

• Nucleotides like ADP are released during sepsis, a condition linked to hypotension and coagulation system activation.
• Sepsis-induced hypotension can lead to disseminated intravascular coagulation.
• The impact of nucleotide-induced cardiovascular collapse on hemostasis requires investigation.

Purpose of the Study:

• To determine if nucleotide-induced cardiovascular collapse affects the hemostatic system.
• To assess the hemostatic changes induced by systemic infusion of adenosine, ADP, ATP, UTP, and nitric oxide.

Main Methods:

• Ten pigs underwent randomized infusions of adenosine, ADP, ATP, UTP, or nitric oxide to induce hypotension.
• Whole blood thromboelastography (TEG) was used to evaluate hemostatic function.
• Endothelial release of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was measured.

Main Results:

• ADP infusion significantly reduced maximum amplitude and angle in TEG, indicating hypocoagulation.
• Increased t-PA release and decreased PAI-1 were observed, but TEG showed no increased fibrinolysis.
• Other infused substrates did not induce significant hypocoagulation.

Conclusions:

• Circulating ADP induces hypocoagulation without evidence of increased fibrinolysis via TEG.
• Systemic ADP may contribute to the coagulopathy observed in severe sepsis.
• Further investigation into the clinical significance of these findings is warranted.