title: Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis.
abstract: OBJECTIVE
  To evaluate the coagulative/fibrinolytic cascade and the circulating markers of the endothelial injury in systemic sclerosis (SSc).
  
  
  METHODS
  Plasma was obtained from 29 patients with SSc and tested for thrombin-antithrombin (TAT), fragments 1+2 (F1+2), dermatansulphate (DS), thrombomodulin (TM), lipoprotein (a) [Lp(a)], von Willebrand factor (vWF), tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimers, intercellular adhesion molecole-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin. The data were correlated with lung (forced vital capacity, diffusing lung capacity for carbon monoxide, vital capacity) and skin (skin score) involvement.
  
  
  RESULTS
  Coagulation was significantly activated (increase in F1+2, P <.001; TAT, P <.01; and Lp(a), P <.05). TM was not significantly different from controls. vWF was significantly increased (P <.01), and its supranormal multimers increased in more than 50% of patients. DS was significantly increased in diffuse cutaneous SSc (P <.01). Fibrinolysis was impaired as shown by reduced D-dimers (P <.01) and decreased levels of PAI (P < 0.01). The markers of endothelial injury were also significantly elevated. DS correlated significantly with forced vital capacity (P <.01) and forced vital capacity ratio (P <.01).
  
  
  CONCLUSIONS
  Injury to the endothelium reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway. The loss of the balance between fibrinolysis and coagulation contributes to vessel engulfment with fibrin and breakdown of vessel patency. The increase of circulating DS suggests that this factor may be a new marker of endothelial injury.
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Florence, Italy. cerinic@unifi.it
authors.forename: Marco Matucci
authors.initials: MM
authors.lastname: Cerinic
authors.forename: G
authors.initials: G
authors.lastname: Valentini
authors.forename: G G
authors.initials: GG
authors.lastname: Sorano
authors.forename: S
authors.initials: S
authors.lastname: D'Angelo
authors.forename: G
authors.initials: G
authors.lastname: Cuomo
authors.forename: L
authors.initials: L
authors.lastname: Fenu
authors.forename: S
authors.initials: S
authors.lastname: Generini
authors.forename: S
authors.initials: S
authors.lastname: Cinotti
authors.forename: M
authors.initials: M
authors.lastname: Morfini
authors.forename: A
authors.initials: A
authors.lastname: Pignone
authors.forename: S
authors.initials: S
authors.lastname: Guiducci
authors.forename: A
authors.initials: A
authors.lastname: Del Rosso
authors.forename: R
authors.initials: R
authors.lastname: Kalfin
authors.forename: D
authors.initials: D
authors.lastname: Das
authors.forename: F
authors.initials: F
authors.lastname: Marongiu
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D015415:Biomarkers