Hirudin as a molecular probe for thrombin in vitro and during systemic coagulation in the pig

The amount of thrombin active in vivo in the intravascular space (blood and endothelial surface), both basally and in experimental intravascular coagulation, is measured by way of the accessibility of thrombin to intravascular hirudin. Blood samples from pigs given intravenous 125I-labeled hirudin contain 125I-labeled hirudin-thrombin complex in concentrations indicative of a basal thrombin concentration in vivo of 0.5 nmol/liter. Intravenous infusion of Salmonella endotoxin elicits an increase in the circulating concentration of hirudin-thrombin complex that begins within 15 min and is 20-30 times basal after 4 hr. Induction of mild intravascular coagulation is evidenced by a modest reduction in plasma fibrinogen concentrations. It is concluded that there is a basal pool of hirudin-accessible thrombin in the intravascular space that, were it free in the plasma phase, would be sufficient in principle to sustain intravascular coagulation.