The role of endothelial cell injury in thrombotic microangiopathy

Am J Kidney Dis. 2010 Dec;56(6):1168-74. doi: 10.1053/j.ajkd.2010.06.006. Epub 2010 Sep 16.


Thrombotic microangiopathy (TMA) refers to a clinical and pathologic syndrome in which endothelial injury results in the manifestations of thrombocytopenia, microangiopathic hemolytic anemia, and kidney injury. A host of causes may induce endothelial injury and TMA, including enteric bacterial toxins, deficiency or dysfunction of complement regulatory proteins, deficiency or inhibition of von Willebrand factor-cleaving proteases, and factors that inhibit endothelial cell proliferation and turnover. This has led specialists to concentrate on these specific inciting factors in terms of designing treatment and management. However, a key and less recognized factor is the underlying level of endothelial health. Many persons with hereditary causes may remain disease free for years or may never develop disease. Others with acute inciting events, such as Escherichia coli O157 enteritis, never manifest TMA. Experimental studies document the importance of specific factors, such as endothelial nitric oxide levels, in helping protect animals from TMA. This suggests that one might approach the management of TMA not simply with specific treatments aimed at the underlying hereditary cause or inciting event, but rather at general measures that may improve overall endothelial health. We propose studies to determine whether interventions that improve endothelial health, such as the administration of angiotensin-converting enzyme inhibitors, statins, vitamin C, allopurinol, or nitric oxide-producing drugs, may be able to prevent TMA, even in persons with underlying hereditary conditions that otherwise would predispose them to these diseases.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Atypical Hemolytic Uremic Syndrome
  • Endothelium, Vascular / injuries*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Hemolytic-Uremic Syndrome / physiopathology
  • Hemolytic-Uremic Syndrome / therapy
  • Humans
  • Nitric Oxide
  • Plasma Exchange
  • Thrombotic Microangiopathies / etiology
  • Thrombotic Microangiopathies / physiopathology*
  • Thrombotic Microangiopathies / therapy
  • Treatment Outcome


  • Nitric Oxide