Recombinant human antithrombin prevents xenogenic activation of hemostasis in a model of pig‐to‐human kidney transplantation

• DOI: 10.1111/xen.12104
• Publication Date: 2014-05-08T07:06:57Z
• Authors: Wolf Ramackers; Lars Friedrich; Johannes Klose; Florian Vondran; Sabine Bergmann; Wolfgang Schüttler; Kai Johanning; Sonja Werwitzke; Arne Trummer; Verena Bröcker; Jürgen Klempnauer; Michael Winkler; Andreas Tiede
• Keywords: Ex vivo; Xenotransplantation; Thrombotic microangiopathy

Xenogenic activation of hemostasis (XAH) represents a major hurdle for the transplantation discordant animal organs into humans as it results in thrombotic microangiopathy (TMA). We have previously shown that recombinant human-activated protein C (rhAPC) mitigates XAH and TMA an ex vivo model pig-to-human kidney transplantation. However, use rhAPC may not be feasible perioperative setting due to possible bleeding complications.Here, we explored effects another natural inhibitor coagulation, human antithrombin (rhAT), comparison with rhAPC. Unmodified porcine kidneys (n = 25) were perfused blood, or blood supplemented rhAT. Surrogate parameters organ survival, markers (D- Dimer, thrombin-antithrombin complex [TAT], fibrinogen, activity, plasminogen), endothelial cell platelet (E-selectin, P-selectin), function tests histological signs evaluated.Perfusion was > 240 min all experiments autologous but limited 126 ± 78 increased vascular resistance. Addition rhAT protected from allowed perfusion times min. In addition, there less reduced release P-selectin overexpression E-selectin, whereas progressive loss function, observed during perfusion, prevented. The effect dose-dependent maximum protection obtained at 3 IU/ml.In conclusion, this xenotransplantation, prevented doses appear clinical preclinical settings.