CROSS-REACTIVITY OF HUMAN MOLECULAR MARKERS FOR DETECTION OF PRETHROMBOTIC STATES IN VARIOUS ANIMAL SPECIES

The aim of the present study was to investigate the reactivity of immu noreagents developed for clinical applications in humans in different animal species (hen, mouse, rat, rabbit, guinea-pig, dog, pig, sheep, baboon). Prothrombin fragment 1 + 2, thrombin-antithrombin III complex and fibrinopeptide A were tested for coagulation, platelet factor 4 a nd beta-thromboglobulin for platelet activation, glycoprotein IIb-IIIa , glycoprotein Ib and P-selectin for platelet membrane glycoproteins, D-dimers for fibrinolysis, thrombomodulin for activation of endothelia l cells and thrombospondin and von Willebrand factor for adhesive prot eins. Prothrombin fragment 1 + 2, platelet factor 4, beta-thromboglobu lin and D-dimers were revealed only in baboons. Fibrinopeptide A was w ell detected in baboons but weakly in mice, dogs, pigs and sheep. Wher eas glycoprotein IIb-IIIa was revealed on guinea-pig, dog and sheep pl atelets and glycoprotein Ib on rabbit and dog platelets, P-selectin an d thrombomodulin were never detected. Thrombospondin was revealed in h ens, mice, rats, guinea-pigs, pigs, sheep and baboons and von Willebra nd factor in mice, rats, guinea-pigs, dogs, pigs, sheep and baboons. I nterestingly, thrombin-antithrombin III complex (TAT) was detected in all species tested except the hen. A time- and dose-dependent increase in TAT was observed when mts, dogs or pigs were infused with thrombop lastin (4.5-450 mu l/kg/h), while administration of hirudin (1 mg/kg) abolished this TAT generation. Thus, the TAT immuno-assay could provid e a tool for the screening of antithrombotic drugs in a number of anim al species. However, the possibility of using a wider panel of human i mmunoreagents would appear to be restricted to baboons which display g ood species cross-reactivity.