A narrative review of transplant-associated thrombotic microangiopathy: pathogenesis and novel therapies

Abstract

Background and Objective: Hematopoietic stem cell transplantation (HSCT) is the only cure for most hematologic disorders. Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication after HSCT. It has a high morbidity and mortality rate relative to other post-transplant complications. We summarize in this review the pathogenesis of TA-TMA as reported in previous studies and some of the current novel therapeutic approaches in the hope of providing ideas for treating this disease. Methods: We collected published literature related to TA-TMA up to August 2022 from databases including PubMed and Embase to summarize the pathogenesis, treatment, and outlook of TA-TMA, combined with our own studies related to TA-TMA. All the publications referred are in English. Key Content and Findings: Microvascular thrombosis due to endothelial cell injury raised from multiple causes may be its primary pathophysiological process. Disturbances in the oxidative microenvironment, complement dysregulation, microvascular hemolytic anemia, and endothelial injury may lead to multi-organ failure and death. The initial onset of the disease is often difficult to differentiate from other post-transplant disorders such as graft-versus-host disease and hepatic vein occlusive disease, which delays the diagnosis. Recent studies have shown that complement is a major pathogenic factor in TA-TMA, and complement blockers have potential therapeutic value for TA-TMA. Eculizumab was an effective treatment, and the Food and Drug Administration (FDA) has granted narsoplimab priority review. Additional interventions targeting the oxidative microenvironment, such as N-acetylcysteine, have also been reported to be effective against TA-TMA treatment in individual cases. Conclusions: TA-TMA is a severe complication after HSCT with high morbidity and mortality, for which the pathogenesis is not yet clear, and treatments are not fully effective. Many new therapies include new complement blockers and emerging prevention methods. Further elucidation of the disease’s risk factors, and pathophysiology will provide the theoretical basis for additional prevention and treatment options.