Thrombocytopenia after pig‐to‐baboon liver xenotransplantation: where do platelets go?

Abstract

Following liver xenotransplantation, the early disappearance of platelets from the circulation was at least in part due to their aggregation with circulating WBC, which may augment their deposition in the liver xenograft and native lungs. Prevention of platelet aggregation with monocytes and neutrophils is likely beneficial in reducing their subsequent sequestration in the liver xenograft and native organs.

Porcine Extrahepatic Vascular Endothelial Asialoglycoprotein Receptor 1 Mediates Xenogeneic Platelet Phagocytosis In Vitro and in Human-to-Pig Ex Vivo Xenoperfusion

“…In a recent study, high amounts of platelet-platelet and platelet-WBC aggregates were found and linked to low apparent platelet counts. 7,11 In the present study, we also observed platelet-WBC aggregation after 10 and 20 minutes of incubation of whole, non-anticoagulated human blood with PAEC grown on microcarrier beads. These data suggest that platelet aggregation with WBC might be a common phenomenon in pigto-primate xenotransplantation or xenoperfusion.…”

“…8 Transplantation of organs from α1,3-galactosyltransferasegene-knockout(GalTKO)orGalTKO and human CD46 transgenic pigs also led to thrombocytopenia throughout the posttransplant period. 11 Determination of the mechanisms responsible for this thrombocytopenia is necessary for the development of preventive strategies. In this study, we have shown the expression of ASGR1, a known platelet binding C-type lectin receptor, in PAEC as well as PFAEC.…”

“…10 Platelet activation and aggregation are critical events that might precede the development of thrombocytopenia and/or sequestration of platelets in xenografts. 11 However, platelet phagocytosis by endothelial cells through receptor-ligand interactions cannot be excluded. Recently, it has been shown that porcine Kupffer cells and liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets in ex vivo perfusion systems.…”

Pig Liver Xenotransplantation

“…Platelet loss and platelet/leukocyte aggregation would appear to be a major problem. 21,39 However, if the native liver remains in situ , the production of primate coagulation factors leads to the development of thrombotic microangiopathy in the graft, resulting in ischemic injury and graft destruction (just as in pig heart and kidney xenografts).…”

“…Evidence has been presented to indicate that (i) primate platelets are phagocytosed by pig liver macrophages (Kupffer cells) and sinusoidal endothelial cells, 20–23,44 or (ii) may be lost in platelet-leukocyte aggregates in the graft and in certain recipient organs. 20,39 …”