Circulating endothelial cells and progenitors as prognostic factors during autoimmune thrombotic thrombocytopenic purpura: results of a prospective multicenter French study

J Thromb Haemost. 2014 Oct;12(10):1601-9. doi: 10.1111/jth.12681. Epub 2014 Sep 22.

Abstract

Background: Autoimmune thrombotic thrombocytopenic purpura (AI-TTP) is characterized by an excess of circulating ultralarge von Willebrand factor (VWF) caused by anti-ADAMTS-13 autoantibodies. Animal studies, however, have shown that endothelial cell activation may also be an important trigger of AI-TTP.

Objectives: To prospectively study circulating biomarkers of endothelial lesion and activation, such as circulating endothelial cells (CECs), soluble P-selectin (sP-selectin), or VWF, and of endothelial repair, such as circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs), in AI-TTP, in relation to disease severity and prognosis.

Results: Twenty-two patients were included in this study. CEC (P < 0.01), VWF (P < 0.05) and sP-selectin (P < 0.01) levels were significantly increased during crisis, and returned to baseline levels during remission. Both CEC (P < 0.05) and sP-selectin (P < 0.05) levels were significantly higher in patients who died or developed neurologic sequelae. CPC levels were substantially increased during the acute phase of the disease (P < 0.001), and returned to baseline levels during remission. Among CPCs, EPC levels were also increased during crisis (P < 0.05) and significantly decreased during remission. Patients who received < 16 plasma exchanges (PEs) had significantly higher EPC counts (P < 0.05) than those who needed more numerous PEs to obtain remission, suggesting that initial EPC counts may be associated with faster endothelial repair.

Conclusion: The profile of circulating endothelial markers shows massive endothelial activation and repair/remodeling during AI-TTP, and suggests that CECs and EPCs may be promising prognostic biomarkers of the disease.

Keywords: P-selectin; endothelium; prospective studies; purpura; stem cells; thrombotic thrombocytopenic.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Autoimmune Diseases / blood*
  • Autoimmune Diseases / therapy
  • Biomarkers / metabolism
  • Endothelial Cells / cytology*
  • Female
  • France
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Prognosis
  • Prospective Studies
  • Purpura, Thrombotic Thrombocytopenic / blood*
  • Purpura, Thrombotic Thrombocytopenic / therapy
  • Remission Induction
  • Stem Cells / cytology*
  • Young Adult
  • von Willebrand Factor / metabolism

Substances

  • Biomarkers
  • P-Selectin
  • von Willebrand Factor