Posttransplant thrombotic microangiopathy: sensitivity of proposed new diagnostic criteria

Abstract

Objective diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA) has traditionally been difficult due to the multiple potential etiologies of thrombocytopenia and red blood cell fragmentation occurring after allogeneic hematopoietic stem cell transplantation (SCT). To attempt to address this issue of diagnostic uncertainty, two new diagnostic criteria for TA-TMA have recently been proposed: the Bone Marrow Transplant Clinical Trials Network (BMT-CTN) and the International Working Group (IWG) criteria. However, both newly proposed criteria are yet to be clinically validated. All 15 cases of TA-TMA previously diagnosed at the authors' institution between December 2001 and March 2008 were retrospectively reclassified under the newly proposed BMT-CTN and IWG criteria. Potential diagnostic pitfalls were identified in both the BMT-CTN and the IWG TA-TMA criteria. The main limitation of the BMT-CTN criteria appeared to be need for concurrent renal and/or neurologic dysfunction to be manifest at TA-TMA diagnosis, which was present in only 73% of our patient cohort. For the IWG criteria, the main limitation to TA-TMA diagnosis appeared to be the requirement for schistocytosis of more than 4%, which was present in only 27% of these patients. Our experience suggests that potentially significant diagnostic pitfalls remain with both recently proposed TA-TMA diagnostic criteria, pitfalls that are likely to limit the diagnostic sensitivity of both. It is recommended that further clinical correlation of both the BMT-CTN and the IWG criteria be undertaken before either is routinely adapted into SCT practice.