gms | German Medical Science

Introduction: During pig-to-primate xenotransplantation aberrant activation of coagulation (AAC) can be observed causing disseminated intravascular coagulation (DIC). It is still controversial if AAC is an epiphenomenon of ongoing rejection or mediated by an independent pathomechanism. Thus, the aim of this study was to analyze the influence of xenoreactive antibodies (XRA) on AAC.

Materials and methods: In an ex vivo perfusion system porcine kidneys (n=10) were perfused with human blood. The experiments were performed in three different groups: perfusion with porcine blood (1), with human blood without pharmacological intervention (2) or addition of recombinant human activated protein C (rhAPC) (3). Donor sera were collected before the perfusion was started and XRA titers were detected by flowcytometry. Blood tissue samples were obtained after termination of the perfusion experiments.

Results: Perfusion in group 1 was not restricted. Analyses of blood and tissue samples revealed neither signs for AAC nor deposition of IgM/IgG and low XRA titer. Perfusion in group 2 was limited showing AAC and IgM/IgG deposits; XRA titers were high. Group 3 showed prolonged perfusion times without signs for AAC. However, strong IgM/IgG deposits were detected. XRA titers were high.

Conclusion: In this study we analyzed the effect of XRA on AAC. Xenogenic perfusion alone caused AAC in all experiments. However, C3a levels did not correlate with the grade of derangement. The Addition of rhAPC abolished AAC despite high XRA titers. C3a levels and XRA titers were comparable to those of group 2. At least in this model AAC is not dependent on XRA titer or complement activation but on adequate anti-coagulative therapy.