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Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy.

Abstract
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.
AuthorsOsama Elsallabi, Vijaya Raj Bhatt, Prajwal Dhakal, Kirk W Foster, Ketki K Tendulkar
JournalClinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis (Clin Appl Thromb Hemost) Vol. 22 Issue 1 Pg. 12-20 (Jan 2016) ISSN: 1938-2723 [Electronic] United States
PMID26239316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Copyright© The Author(s) 2015.
Chemical References
  • Rituximab
Topics
  • Female
  • Graft vs Host Disease (diagnosis, etiology, pathology, therapy)
  • Hematopoietic Stem Cell Transplantation (adverse effects)
  • Humans
  • Male
  • Plasma Exchange
  • Risk Factors
  • Rituximab (therapeutic use)
  • Thrombotic Microangiopathies (diagnosis, etiology, pathology, therapy)
  • Transplantation Conditioning

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