Interspecies variation in the cellular phase of blood fibrinolytic activity

In normal humans, whole blood fibrinolytic activity is three to six times greater than that of companion plasma. This additional activity derives from neutrophil enzymes, with possible contributions from other cell types. Rats and dogs are frequently used to study fibrinolysis in animal models of human disease. Compared with humans, rats are relatively neutropenic, whereas dogs have a relative neutrophilic leukocytosis. Interspecies variation in cellular phase fibrinolytic activity has not been examined. We therefore determined whole blood, plasma, and cellular phase fibrinolytic activity in 27 rats and 6 dogs, using a 125I-fibrin solid phase assay. Whole blood and plasma activities were similar in rats, consistent with very low cellular activity. Dogs, however, had high cellular phase activity, making up an average 91% of whole blood activity. These results suggest that blood fibrinolytic mechanisms in rats differ from those in humans and dogs, and that this difference should be considered when studying fibrinolysis in models of human disease.