ADAMTS13 activity in sickle cell disease

Am J Hematol. 2006 Jul;81(7):492-8. doi: 10.1002/ajh.20653.

Abstract

Sickle red blood cell (SRBC)-endothelial adhesion plays a central role in sickle cell disease (SCD)-related vaso-occlusion. As unusually large von Willebrand factor (ULVWF) multimers mediate SRBC-endothelial adhesion, we investigated the activity of ADAMTS13, the metalloprotease responsible for cleaving ULVWF multimers, in SCD. ADAMTS13 activity was determined using a quantitative immunoblotting assay. VWF:Ag and VWF:RCo were determined using commercial assays. The high-molecular-weight VWF multimer percentage was determined by employing gel electrophoresis. ADAMTS13 activity was similar among asymptomatic patients (n = 8), patients at presentation with a painful crisis (n = 23), and healthy controls. ADAMTS13/VWF:Ag ratios were lower in patients compared to healthy HbAA controls, with the lowest values at presentation with a painful crisis (P = 0.02). Division of samples in those with VWF:RCo/VWF:Ag ratios < 0.70 and those with ratios >or= 0.70 revealed significantly more samples with ratios >or= 0.70 (P = 0.01) collected during painful crises. ULVWF multimers were detected in 6 patient samples and in 1 control sample. ADAMTS13/VWF:Ag ratios were inversely related to the duration of symptoms at presentation with an acute vaso-occlusive event (r(s)-0.67, P = 0.002). Although SCD is characterized by elevated VWF:Ag levels, no severe ADAMTS13 deficiency was detected in our patients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • ADAM Proteins / blood*
  • ADAM Proteins / deficiency
  • ADAMTS13 Protein
  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / enzymology
  • Anemia, Sickle Cell / pathology
  • Blotting, Western
  • Cell Adhesion
  • Child
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / pathology
  • Erythrocytes, Abnormal / enzymology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / blood
  • Pain / etiology
  • Vascular Diseases / blood
  • Vascular Diseases / etiology
  • von Willebrand Factor / analysis

Substances

  • Multienzyme Complexes
  • von Willebrand Factor
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human