Translating biomarker insights into practice: a path forward in TA-TMA management

Recent advances in the management of transplant-associated thrombotic microangiopathy (TA-TMA) include the harmonization of diagnostic criteria and the identification of high-risk disease features. Individual hematologic and complement biomarkers show moderate specificity when used alone in the dete...

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Main Authors: Sonata Jodele, Eleni Gavriilaki
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1550365/full
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author Sonata Jodele
Eleni Gavriilaki
author_facet Sonata Jodele
Eleni Gavriilaki
author_sort Sonata Jodele
collection DOAJ
description Recent advances in the management of transplant-associated thrombotic microangiopathy (TA-TMA) include the harmonization of diagnostic criteria and the identification of high-risk disease features. Individual hematologic and complement biomarkers show moderate specificity when used alone in the detection of TA-TMA in hematopoietic stem cell transplant (HSCT) recipients, but the identification of endothelial injury due to microangiopathic process can be enhanced using longitudinal monitoring of biomarkers and clinical features. An increase in the sC5b-9 level reflects terminal complement activation, a hallmark of TA-TMA pathogenesis that guides therapeutic interventions. In addition, distinguishing physiologic from pathologic complement activation is essential for timely diagnosis of the disease and selection of targeted interventions. Eculizumab therapy, a biomarker-guided C5 blocker, significantly improves clinical outcomes in severe TA-TMA; however, there is a lack of knowledge on how to select second-line complement inhibitors or combination therapies for cases with a suboptimal response to eculizumab. This article proposes practical approaches to increasing the specificity and attributability of TA-TMA diagnostic biomarkers by integrating clinically available supportive diagnostic tests and provides insights into potential biomarkers for currently available novel complement inhibitors. These findings help ensure timely diagnosis, prevent irreversible organ injury, and improve outcomes in HSCT recipients with TA-TMA.
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spelling doaj-art-b5e76e8ee5b447a2a9d77690d12e5ce92025-08-20T02:57:26ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15503651550365Translating biomarker insights into practice: a path forward in TA-TMA managementSonata Jodele0Eleni Gavriilaki1Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cancer and Blood Disease Institute, University of Cincinnati College of Medicine, Cincinnati, OH, United States2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceRecent advances in the management of transplant-associated thrombotic microangiopathy (TA-TMA) include the harmonization of diagnostic criteria and the identification of high-risk disease features. Individual hematologic and complement biomarkers show moderate specificity when used alone in the detection of TA-TMA in hematopoietic stem cell transplant (HSCT) recipients, but the identification of endothelial injury due to microangiopathic process can be enhanced using longitudinal monitoring of biomarkers and clinical features. An increase in the sC5b-9 level reflects terminal complement activation, a hallmark of TA-TMA pathogenesis that guides therapeutic interventions. In addition, distinguishing physiologic from pathologic complement activation is essential for timely diagnosis of the disease and selection of targeted interventions. Eculizumab therapy, a biomarker-guided C5 blocker, significantly improves clinical outcomes in severe TA-TMA; however, there is a lack of knowledge on how to select second-line complement inhibitors or combination therapies for cases with a suboptimal response to eculizumab. This article proposes practical approaches to increasing the specificity and attributability of TA-TMA diagnostic biomarkers by integrating clinically available supportive diagnostic tests and provides insights into potential biomarkers for currently available novel complement inhibitors. These findings help ensure timely diagnosis, prevent irreversible organ injury, and improve outcomes in HSCT recipients with TA-TMA.https://www.frontiersin.org/articles/10.3389/fmed.2025.1550365/fulltransplant-associated thrombotic microangiopathybiomarkerscomplementeculizumabravulizumabnarsoplimab
spellingShingle Sonata Jodele
Eleni Gavriilaki
Translating biomarker insights into practice: a path forward in TA-TMA management
Frontiers in Medicine
transplant-associated thrombotic microangiopathy
biomarkers
complement
eculizumab
ravulizumab
narsoplimab
title Translating biomarker insights into practice: a path forward in TA-TMA management
title_full Translating biomarker insights into practice: a path forward in TA-TMA management
title_fullStr Translating biomarker insights into practice: a path forward in TA-TMA management
title_full_unstemmed Translating biomarker insights into practice: a path forward in TA-TMA management
title_short Translating biomarker insights into practice: a path forward in TA-TMA management
title_sort translating biomarker insights into practice a path forward in ta tma management
topic transplant-associated thrombotic microangiopathy
biomarkers
complement
eculizumab
ravulizumab
narsoplimab
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1550365/full
work_keys_str_mv AT sonatajodele translatingbiomarkerinsightsintopracticeapathforwardintatmamanagement
AT elenigavriilaki translatingbiomarkerinsightsintopracticeapathforwardintatmamanagement