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Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic rates.

Abstract
Platelets are activated in sickle cell disease (SCD), and particularly during vaso-occlusive episodes (VOE). Thrombospondin-1 (TSP1), a major secretory product of activated platelets, is increased in the circulation in VOE and binds to sickle red blood cells (RBC) promoting vascular adhesion. Thus, we hypothesized that TSP1 may represent a plasma biomarker of disease severity in SCD. We tested the plasma collected from patients in steady state (n = 27) and VOE (n = 14), as well as healthy controls (n = 17) at the University of Pittsburgh Medical Center (UPMC), and from patients in steady state enrolled in the walk-PHaSST clinical trial (n = 483). We found that TSP1 levels were increased in VOE in the UPMC cohort. Among steady-state patients at UPMC, TSP1 values correlated positively with lifetime history of acute chest syndrome (r = 0.72, P < 0.0001) and hemoglobin concentration (r = 0.49, P = 0.01), and negatively with markers of hemolysis, such as LDH (r = -0.50, P = 0.009). Analysis of the walk-PHaSST cohort also showed a positive association between TSP1 levels and hydroxyurea use (r = 0.14, P = 0.003), and confirmed the negative associations with the severity of hemolysis. Our results suggest that TSP1 levels are associated with more VOE, hydroxyurea use and lower rates of hemolysis. High TSP1 concentrations may indicate higher risk of the viscosity/vaso-occlusion phenotype of SCD.
AuthorsEnrico M Novelli, Gregory J Kato, Margaret V Ragni, Yingze Zhang, Mariana E Hildesheim, Mehdi Nouraie, Suchitra Barge, Michael P Meyer, Andrea Cortese Hassett, Victor R Gordeuk, Mark T Gladwin, Jeffrey S Isenberg
JournalAmerican journal of hematology (Am J Hematol) Vol. 87 Issue 3 Pg. 326-30 (Mar 2012) ISSN: 1096-8652 [Electronic] United States
PMID22318901 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antisickling Agents
  • Biomarkers
  • Hemoglobins
  • Thrombospondin 1
  • L-Lactate Dehydrogenase
  • Hydroxyurea
Topics
  • Acute Chest Syndrome (epidemiology, etiology)
  • Adult
  • Anemia, Sickle Cell (blood, complications, drug therapy)
  • Antisickling Agents (therapeutic use)
  • Biomarkers
  • Cohort Studies
  • Female
  • Hemoglobins (analysis)
  • Hemolysis
  • Humans
  • Hydroxyurea (therapeutic use)
  • L-Lactate Dehydrogenase (blood)
  • Leg Ulcer (epidemiology, etiology)
  • Male
  • Middle Aged
  • Osteonecrosis (epidemiology, etiology)
  • Platelet Activation
  • Retrospective Studies
  • Thromboembolism (epidemiology, etiology)
  • Thrombospondin 1 (blood)
  • Vascular Patency

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