Clinical usefulness of diagnostic criteria for transplant-associated thrombotic microangiopathy

Abstract

One major cause of treatment-related death is transplant-associated thrombotic microangiopathy (TA-TMA). Because of difficulties with diagnosis, many criteria for TA-TMA have been defined. Some patients clinically suspected as TA-TMA have been treated as TA-TMA regardless of TA-TMA criteria fulfillment (clinical-TMA). To examine sensitivities of TA-TMA criteria for clinical-TMA, we retrospectively evaluated 160 patients undergoing allogeneic hematopoietic stem cell transplantation by five major TA-TMA criteria and compared them with clinical-TMA. Cumulative incidences of TA-TMA and non-relapse mortality (NRM) were widely diverse between criteria. Thirty-eight patients fulfilled one or more TA-TMA criteria (total-TMA), and 12 of them fulfilled only one criterion. In patients with total-TMA, thrombocythemia, serum creatinine > 1.5 × baseline, and proteinuria were especially repeatedly observed among TA-TMA criteria. Ninety-two percent of clinical-TMA patients were classified as patients with total-TMA, and high NRM incidences were exhibited in patients with total-TMA even without clinical-TMA. Hematopoietic cell transplant-comorbidity index ≥ 3, nutritional risk index < 83.5, and grade II-IV acute graft-versus-host disease were extracted as independent risk factors for total-TMA. TA-TMA summation criteria that can cover most of clinical-TMA patients and high-risk patients of NRM were useful in clinical settings, and items of TA-TMA criteria previously described might be triggers for applying TA-TMA criteria.

Von Willebrand factor as a potential predictive biomarker of early complications of endothelial origin after allogeneic hematopoietic stem cell transplantation

“…This is also the case for complement evaluation, as proposed as a grading biomarker of severity of TA-TMA 37 . Furthermore, endothelial-related complications are sometimes challenging to identify because their recognized diagnostic criteria can be easily confounded with other common conditions related to alloHCT 4,19 . Identifying patients at risk of developing patent endothelial diseases, knowing that all patients experience some degree of endothelial activation, could be a key element in controlling treatment-related morbidity and mortality.…”

“…Vascular endothelial syndrome, mainly mediated by drug toxicity and allogeneic reactivity, is a wellrecognized post-transplant complication and includes a variety of life-threatening complications 1,2 . Its frequency is highly variable depending on the diagnostic criteria used in different studies ranging from 8-35% in the early post-transplant period [2][3][4] . The most common endothelial dysfunctions described after alloHCT include capillary leak syndrome (CLS), engraftment syndrome (ES), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS) and diffuse alveolar hemorrhages (DAH) 1,5 .…”