Hematopoietic stem cell transplant-associated thrombotic microangiopathy: current paradigm and novel therapies

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) remains a difficult complication to address due to its high mortality rate, lack of standard diagnostic criteria and limited therapeutic options. Underscoring this challenge is the complex pathophysiology involved...

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Bibliographic Details
Published in:Bone marrow transplantation (Basingstoke) 2018-02, Vol.53 (2), p.129-137
Main Authors: Khosla, J, Yeh, A C, Spitzer, T R, Dey, B R
Format: Article
Language:English
Subjects:
631/250/1904
631/532/1542
692/699/249/1764
Biomarkers
Care and treatment
Cell Biology
Complement activation
Criteria
Diagnosis
Diagnostic systems
Dosage and administration
Graft-versus-host reaction
Hematology
Hematopoietic stem cell transplantation
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic stem cells
Humans
Hypertension
Immunosuppressive agents
Internal Medicine
Medicine
Medicine & Public Health
Nitric oxide
Pharmacology
Public Health
review
Risk analysis
Risk factors
Stem cell transplantation
Stem Cells
Thrombosis
Thrombotic Microangiopathies - etiology
Thrombotic Microangiopathies - pathology
Thrombotic Microangiopathies - therapy
Thrombotic microangiopathy
Transplantation
Transplantation Conditioning - adverse effects
Transplantation Conditioning - methods
Transplants & implants
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Summary:Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) remains a difficult complication to address due to its high mortality rate, lack of standard diagnostic criteria and limited therapeutic options. Underscoring this challenge is the complex pathophysiology involved and multiple contributing factors that converge on a final pathway involving widespread endothelial injury and complement activation. In addressing our current understanding of TA-TMA, we highlight the risk factors leading to endothelial damage and a pathophysiological cascade that ensues. We have also compared the different definition criteria and biomarkers that can enable early intervention in TA-TMA patients. Current first-line management includes discontinuation or alteration of the immunosuppressive regimen, treatment of co-existing infectious and GVHD, aggressive hypertension control and supportive therapy. We discuss current pharmacological therapies, including newer agents that target the complement cascade and nitric oxide pathways.
ISSN:0268-3369
1476-5365
DOI:10.1038/bmt.2017.207