Summary
Many animals are used in research on blood coagulation and fibrinolysis, but the relevance
of animal models to human health is often questioned because of differences between
species. The objective was to find an appropriate animal species
,
which mimics the coagulation profile in humans most adequately. Species differences
in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin
generation was measured in platelet-poor plasma. Measurements were performed in blood
from five different species: humans, rats, pigs, sheep and rabbits. In humans and
sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation
and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening
in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05).Similarly,
the endogenous thrombin potential (ETP) was in the same range in humans and sheep.
The maximum clot firmness with or without thrombin stimulation was similar in rabbits
and humans. The maximum lysis with or without thrombin stimulation was similar in
humans and pigs. Significant species differences exist in the coagulation profile
with or without thrombin stimulation. Most importantly, sheep had a clotting time
most similar to humans and could thus be a suitable species for translational coagulation
studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental
species to study fibrinolytic pathway and support the usefulness of rabbits as a species
for examining platelets.
Keywords
Clotting time - endogenous thrombin potential - species differences - thrombin