Thrombomodulin and Endothelial Dysfunction: A Disease-Modifier Shared between Malignant Hypertension and Atypical Hemolytic Uremic Syndrome

Nephron. 2018;140(1):63-73. doi: 10.1159/000490201. Epub 2018 Jun 25.


Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood vessels. Five percent of all patients with atypical hemolytic uremic syndrome (aHUS) have mutations in the gene coding for TM, with a peak presentation in young children. Mutations often translate into quantitative and qualitative abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS is relatively poor with frequent relapses after transplantation despite its membrane-bound character. We observed a woman presenting with malignant hypertension (MHT) and associated kidney, brain, cardiac, and hematological involvement with thrombotic microangiopathy on kidney biopsy. She had a documented mutation of the gene coding for TM, which was associated with both aHUS and an increased risk for venous and arterial thrombosis. As TM has anti-coagulant, anti-inflammatory, and cytoprotective properties and also attenuates alternative complement activation, this glycoprotein could play an active role in other diseases with endothelial involvement apart from aHUS. We discuss the potential role of TM in the pathophysiology of various endotheliopathies including MHT. We also provide a framework for future therapeutic options.

Keywords: Endothelial; Malignant hypertension; Thrombomodulin; Thrombotic microangiopathy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Atypical Hemolytic Uremic Syndrome / genetics*
  • Atypical Hemolytic Uremic Syndrome / pathology
  • Atypical Hemolytic Uremic Syndrome / physiopathology
  • Child
  • Child, Preschool
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Hypertension, Malignant / genetics*
  • Hypertension, Malignant / pathology
  • Hypertension, Malignant / physiopathology
  • Kidney / pathology
  • Thrombomodulin / genetics*
  • Thrombomodulin / metabolism
  • Thrombomodulin / therapeutic use
  • Thrombotic Microangiopathies / complications
  • Thrombotic Microangiopathies / genetics*
  • Thrombotic Microangiopathies / pathology


  • THBD protein, human
  • Thrombomodulin