Hemostatic status in long-term surviving xenografts.
BACKGROUND
Liver xenotransplantation presents, apart from immunologic problems, metabolic incompatibilities between species. The liver plays a key role in blood coagulation. The aim of this study is to describe the hemostatic status of long-term surviving xenografts in a hamster-to-rat liver xenotransplantation model.


METHODS
Orthotopic liver transplantation with Tacrolimus and MMF was carried out with Golden Syrian hamsters, Brown Norway, or Dark Agouti rats as donors and Lewis rats as recipients. Prothrombine time (PT), activated partial thromboplastin time (APTT), antithrombin, protein-C, free protein-S, TAT-complexes, and factors V and VIII were assessed using standard methods.


RESULTS
Protein-C was absent in rats, but values in xenotransplanted animals increased progressively toward those recorded in hamsters. Xenotransplanted animals also acquired PT, APTT, free protein-S, and antithrombin levels similar to those of donors and we observed a substantial activation of coagulation especially 7 days post-transplantation. Despite TAT high levels, we did not find thrombotic alterations in the histologic analysis of grafts.


CONCLUSIONS
These results reflect a destabilization of the thrombotic-hemostatic balance, not associated with consumption coagulopathy, which gradually disappears. This deregulation is a general imbalance resulting from the replacement of all the components of hepatic synthesis. After 100 days of xenotransplantation, the absence of symptoms of thrombosis or hemorrhage suggests that the change of hemostatic status takes place under conditions of relative equilibrium.
Molleví
David G
DG
Department of Surgery and Surgical Specialties, University of Barcelona School of Medecine Campus Bellvitge, L'Hospitalet de Llobregat, Barcelona, Catalonia. dgmollevi@iconcologia.net
Ginestà
Mireia M
MM
Domenech
Pere
P
Serrano
Teresa
T
Figueras
Joan
J
Jaurrieta
Eduard
E
D000818:Animals; D000990:Antithrombin III; D006224:Cricetinae; D006085:Graft Survival; D006487:Hemostasis; D008297:Male; D008647:Mesocricetus; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood; D011486:Protein C / Q000032:analysis; D011517:Prothrombin Time; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000401:mortality
D011486:Protein C; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases