P230 Clinicopathological Correlation of Transplant Associated Thrombotic Microangiopathy Miriam Berry1, Victoria Bardsley2, Meryl Griffiths2, Sathia Thiru2, Nicholas Torpey1, Verena Broecker2 1 2 Transplant Unit, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United Kingdom Introduction: Transplant associated thrombotic microangiopathy (TA-TMA) is found in about 1% of renal transplant biopsies. Many factors may contribute to aetiology and there are often discrepancies between the histological, clinical and serological findings at the time of diagnosis. This uncertainty has significant therapeutic implications. Methods: We performed a database search to identify all transplant patients diagnosed with TMA since 2008. Index biopsies were re-evaluated and scored using Banff criteria. Pathological characteristics of TMA were assessed. All previous and subsequent histopathological, clinical and serological data were reviewed and a final causal diagnosis was established following clinicopathological conference. Diagnosis of calcineurin inhibitor (CNI) toxicity was based on the absence of histopathological or clinical evidence of any other cause of TMA and improvement following CNI withdrawal. Results: We identified 22 patients with TA-TMA and reviewed 84 renal transplant biopsies, 40 of which showed TA-TMA. 85% were diagnosed within 12 months of transplantation. Patients with ESRF due to immunological disease were over-represented in our cohort (45%), as were recipients of HLA or ABO antibody incompatible grafts (23%). Antibody Mediated Rejection (AMR) and CNI toxicity were the two commonest causes of TATMA (41% and 36%, respectively). Histopathological characteristics of TA-TMA were not significantly different between these groups. In 5/13 patients with DSA, TA-TMA occurred in the absence of microcirculation injury (C4d positive in 4/5 cases). All were considered as a manifestation of AMR in the presence of significant DSA. 10/22 patients showed acute vascular rejection in at least one of their biopsies (3 Banff v1 lesions, 4 Banff v2, 3 Banff v3). In 2 patients this T cell mediated rejection (TCMR) was the only likely cause of TMA. Neither had detectable DSA at any time. The outcome was bimodal; 6/22 patients reached end stage renal failure while the remainder returned to baseline renal function. 5/6 graft losses had AMR. Conclusions: Morphological characteristics of TA-TMA are of limited value in identifying the underlying cause. AMR was the commonest cause of TA-TMA, the only manifestation of AMR in some cases and associated with poor renal outcomes. CNI related disease responded to drug withdrawal and this group had much better renal outcomes. Cell mediated vascular rejection was seen in 45% patients, indicating the role of endothelial injury in a multifactorial process. Multiple hits are likely to precipitate TMA: underlying susceptibility, vascular injury and an additional trigger such as CNI.