title: Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension.
abstract: BACKGROUND
  Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD.
  
  
  METHODS
  This cross-sectional study was performed using a cohort of patients followed at an adult Sickle Cell Clinic. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age, sex and body mass index-adjusted reference ranges. Clinical laboratory examinations, including hematologic studies and biochemical tests, as well as various measures of coagulation activation, endothelial activation and inflammation, were conducted on SCD subjects and on healthy, race-matched control subjects without SCD.
  
  
  RESULTS
  Patients with SCD (n=76) had higher plasma levels of markers of coagulation (thrombin-antithrombin complex, prothrombin fragment F1+2, D-dimer) and endothelial (soluble vascular endothelial cell adhesion molecule, sVCAM) activation compared with control subjects (n=6). SCD patients with PHT (n=26) had significantly higher levels of sVCAM compared with those patients without PHT (n=50). Although PHT patients showed increased plasma measures of coagulation activation, the differences were not statistically significant when compared to those of patients without PHT. HbSS patients with PHT also had a trend towards higher levels of other inflammatory cytokines (interleukins 6, 8 and 10) than HbSS patients without PHT. There was a modest negative correlation between hemoglobin and plasma measures of coagulation and endothelial activation, and modest positive correlations between markers of hemolysis and plasma measures of coagulation and endothelial activation.
  
  
  CONCLUSIONS
  SCD patients with PHT have higher levels of markers of endothelial activation and other inflammatory markers than patients without PHT. A trend towards an increased level of markers of coagulation activation was observed in SCD patients with PHT compared with that in patients without PHT. Markers of hemolysis are associated with coagulation activation and endothelial dysfunction in SCD patients. Clinical trials of anticoagulants and anti-inflammatory agents are warranted in SCD patients with PHT.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, CB# 7305, 3009 Old Clinic Bldg Chapel Hill, NC 27599-7305, USA. kataga@med.unc.edu
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.forename: Charity G
authors.initials: CG
authors.lastname: Moore
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hillery
authors.forename: Susan
authors.initials: S
authors.lastname: Jones
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Whinna
authors.forename: Dell
authors.initials: D
authors.lastname: Strayhorn
authors.forename: Cathy
authors.initials: C
authors.lastname: Sohier
authors.forename: Alan
authors.initials: A
authors.lastname: Hinderliter
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Parise
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Orringer
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000276:immunology*; D001777:Blood Coagulation; D015331:Cohort Studies; D004452:Echocardiography / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000276:immunology*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1