title: Cross-reactivity of human molecular markers for detection of prethrombotic states in various animal species.
abstract: The aim of the present study was to investigate the reactivity of immunoreagents 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 and 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 endothelial cells and thrombospondin and von Willebrand factor for adhesive proteins. Prothrombin fragment 1 + 2, platelet factor 4, beta-thromboglobulin and D-dimers were revealed only in baboons. Fibrinopeptide A was well detected in baboons but weakly in mice, dogs, pigs and sheep. Whereas glycoprotein IIb-IIIa was revealed on guinea-pig, dog and sheep platelets and glycoprotein Ib on rabbit and dog platelets, P-selectin and thrombomodulin were never detected. Thrombospondin was revealed in hens, mice, rats, guinea-pigs, pigs, sheep and baboons and von Willebrand factor in mice, rats, guinea-pigs, dogs, pigs, sheep and baboons. Interestingly, 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 rats, dogs or pigs were infused with thromboplastin (4.5-450 microliters/kg/h), while administration of hirudin (1 mg/kg) abolished this TAT generation. Thus, the TAT immunoassay could provide a tool for the screening of antithrombotic drugs in a number of animal species. However, the possibility of using a wider panel of human immunoreagents would appear to be restricted to baboons which display good species cross-reactivity.
authors.affiliation: INSERM U.311, Etablissement de Transfusion Sanguine, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Ravanat
authors.forename: M
authors.initials: M
authors.lastname: Freund
authors.forename: F
authors.initials: F
authors.lastname: Dol
authors.forename: Y
authors.initials: Y
authors.lastname: Cadroy
authors.forename: J
authors.initials: J
authors.lastname: Roussi
authors.forename: F
authors.initials: F
authors.lastname: Incardona
authors.forename: J P
authors.initials: JP
authors.lastname: Maffrand
authors.forename: B
authors.initials: B
authors.lastname: Boneu
authors.forename: L
authors.initials: L
authors.lastname: Drouet
authors.forename: C
authors.initials: C
authors.lastname: Legrand
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D002645:Chickens; D004285:Dogs; D005260:Female; D005342:Fibrinolysis; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010215:Papio; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013552:Swine; D013925:Thromboplastin / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D013925:Thromboplastin; D010447:Peptide Hydrolases