title: Endothelial function in patients with sickle cell anemia during and after sickle cell crises.
abstract: BACKGROUND
  Prior studies have demonstrated increased adherence of sickle cell erythrocytes to vascular endothelial cells. While decreased production of nitric oxide and increased production of adhesion molecules have been implicated in this pathophysiology, the relative contribution of these mechanisms during acute sickle cell crises as compared to steady state conditions have not been elucidated.
  
  
  RESULTS
  We studied 10 consecutive young adult patients presenting with a sickle cell crisis. Endothelial function was evaluated by a non-invasive brachial artery shear stress method. Serum levels of adhesion molecules were obtained during the crisis. Both brachial artery responsiveness and serum levels of adhesion molecules were then repeated at steady state. Ten age and gender matched volunteers served as a control group. Impaired endothelial function and impaired endothelium-independent vasodilatation were observed in all sickle cell patients during both steady state and during crisis. Flow mediated dilation (FMD)% was 3.25+/- 2.76% during crisis, 4.57+/- 4.11 at steady state, compared with the control group FMD of 11.64+/- 7.69% (p< 0.001). Flow independent dilation was 10.35+/- 11.3% during crisis, 10.03+/- 6.52% at steady state, compared with control group FID of 24.17+/- 11.87% (p< 0.001). Levels of cell adhesion molecules and markers of inflammation were increased in sickle cell crisis patients compared with the control group: sCD40 ligand levels during the acute crisis were over twice the level of normal matched volunteers (p=0.02), and similarly significant increases were seen for E-selectin (p=0.008), ICAM-1 (p=0.037) and VCAM-1 levels (p=0.01). The levels of each of these biomarkers was not significantly increased during acute crises as compared to patients' recovery state.
  
  
  CONCLUSIONS
  Sickle cell anemia patients have severe systemic endothelial dysfunction as demonstrated by both brachial artery assessment and increased serum levels of adhesion molecules. These abnormalities characterize not only the sickle cell crisis but also the steady state pathophysiology of sickle cell anemia.
authors.affiliation: Department of Internal Medicine A, Poria Medical Center, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Blum
authors.forename: Shay
authors.initials: S
authors.lastname: Yeganeh
authors.forename: Aviva
authors.initials: A
authors.lastname: Peleg
authors.forename: Fina
authors.initials: F
authors.lastname: Vigder
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kryuger
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khatib
authors.forename: Khalid
authors.initials: K
authors.lastname: Khazim
authors.forename: Harold
authors.initials: H
authors.lastname: Dauerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery; D023201:CD40 Ligand / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D011446:Prospective Studies; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D023201:CD40 Ligand; D009569:Nitric Oxide