title: Markers of thrombogenesis and fibrinolysis and their relation to inflammation and endothelial activation in patients with idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Chronic anticoagulation is a standard of care in idiopathic pulmonary arterial hypertension (IPAH). However, hemostatic abnormalities in this disease remain poorly understood. Therefore, we aimed to study markers of thrombogenesis and fibrinolysis in patients with IPAH.
  
  
  METHODS
  We studied 27 consecutive patients (67% female) with IPAH aged 50.0 years (IQR: 41.0-65.0) and 16 controls without pulmonary hypertension. Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complexes were measured to assess thrombogenesis; tissue-type plasminogen activator (tPA) antigen and plasmin-anti-plasmin complex to characterize activation of fibrinolysis; plasminogen activator inhibitor 1 (PAI-1) to measure inhibition of fibrinolysis; and endothelin-1 (ET-1) and interleukin-6 (IL-6) to assess endothelial activation and systemic inflammation, respectively. In addition, in treatment-naive IPAH patients these markers were assessed after 3 months of PAH-specific therapies.
  
  
  RESULTS
  TPA (10.1[6.8-15.8] vs 5.2[3.3-7.3] ng/ml, p<0.001), plasmin-anti-plasmin (91.5[60.3-94.2] vs 55.8[51.1-64.9] ng/ml, p<0.001), IL-6 (4.9[2.5-7.9] vs 2.1[1.3-3.8] pg/ml, p=0.001) and ET-1 (3.7 [3.3-4.5] vs 3.4[3.1-3.5], p= 0.03) were higher in patients with IPAH than in controls. In IPAH patients plasmin-anti-plasmin and tPA correlated positively with IL-6 (r=0.39, p=0.04 and r=0.63, p<0.001, respectively) and ET-1 (r=0.55, p=0.003 and r=0.59, p=0.001, respectively). No correlation was found between tPA or plasmin-anti-plasmin and markers of thrombogenesis. Plasmin-anti-plasmin decreased after 3 months of PAH specific therapy while the other markers remained unchanged.
  
  
  CONCLUSIONS
  In the present study we showed that markers of fibrynolysis were elevated in patients with IPAH however we did not find a clear evidence for increased thrombogenesis in this group of patients. Fibrinolysis, inflammation, and endothelial activation were closely interrelated in IPAH.
authors: Department of Cardiac and Vascular Diseases of the John Paul II Hospital in Krakow and the Jagiellonian University Collegium Medicum, Krakow, Poland.
authors: Grzegorz
authors: G
authors: Kopeć
authors: Deddo
authors: D
authors: Moertl
authors: Sabine
authors: S
authors: Steiner
authors: Ewa
authors: E
authors: Stępień
authors: Tomasz
authors: T
authors: Mikołajczyk
authors: Jakub
authors: J
authors: Podolec
authors: Marcin
authors: M
authors: Waligóra
authors: Jakub
authors: J
authors: Stępniewski
authors: Lidia
authors: L
authors: Tomkiewicz-Pająk
authors: Tomasz
authors: T
authors: Guzik
authors: Piotr
authors: P
authors: Podolec
mesh_terms: D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D065627:Familial Primary Pulmonary Hypertension / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D011516:Prothrombin; D013917:Thrombin; D010959:Tissue Plasminogen Activator