Background: Analyses of pancreas transplant outcomes have revealed that pancreatic grafts exhibit an enhanced intolerance to prolonged cold ischaemia time (CIT), however the underlying pathophysiology remains unclear. Previous studies in islet transplantation have highlighted the role of Tissue Factor (TF) production by islets in initiation of detrimental thrombotic reactions. Emerging data also demonstrate the importance of TF-dependent pathways on the death of beta cells in response to pro-inflammatory cytokines. We hypothesise that prolonged pancreatic CIT confers a procoagulant phenotype on the donor organ, resulting in poorer recipient outcomes. The aim of this study was to determine the effect of prolonged CIT on the incidence of graft macrovascular thrombosis.

Methods: A retrospective analysis of all pancreas transplants performed in a single-centre from July 2007 to July 2015 was performed. Data were collected on donor and recipient demographics, length of CIT, intra-operative characteristics and re-operations. A review of all radiological imaging within ten post-operative days was performed to determine the incidence of macrovascular thrombus.

Results: 99 transplants; 69 simultaneous pancreas and kidney, 29 pancreas after kidney and one pancreas transplant alone, were included. The mean age of recipients was 44.1 years (range 24-67 years). Six patients had a previous pancreas transplant, one patient underwent third-time pancreas transplantation. 83.7% of transplants performed were from DBD donors and the median CIT was 16.2 hours. Seventy-six patients underwent computed topography scanning, identifying macrovascular thrombus in 28% of all transplants; (50% arterial, 43% venous, 7% arterial & venous thrombus), resulting in five graft pancreatectomies. The incidence of macrovascular graft thrombosis was 18.2% in transplants performed under the accepted CIT gold standard of 12 hours, whilst transplants reperfused beyond 12 hours had a thrombosis rate of 29.5% (p=ns).

Conclusion: This study, although limited to single institution figures, does suggest an association between prolonged CIT and graft macrovascular thrombosis, indicating potentially injurious procoagulant pathways. This hypothesis is currently being further examined using in-vitro assessment of TF-dependent pathways, and transcriptional and translational profiling of sequential CIT biopsies from donor pancreata allocated for research.

CITATION INFORMATION: Sandhu B, Charitidou S, Vallant N, McLean A, Taube D, DiCocco P, Herbert P, Crane J, Papalois V. Injurious Procoagulant Pathways During Prolonged Cold Storage of the Donor Pancreas. Am J Transplant. 2016;16 (suppl 3).

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