title: Plasma concentrations of tissue factor and its inhibitor in chronic thromboembolic pulmonary hypertension: a step closer to explanation of the disease aetiology?
abstract: BACKGROUND
  The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not clearly understood. In some patients, the disease is preceded by acute pulmonary embolism (APE), and is characterised by intravascular thrombosis, vasoconstriction, inflammation and remodelling of pulmonary arteries. Ensuing pulmonary hypertension leads to potentially fatal chronic right ventricle failure. Both inborn and acquired risk factors were identified. Pathogenesis of haemostatic disorders is not completely explained, and extrinsic coagulation pathway disorders may play a role in CTEPH aetiology.
  
  
  OBJECTIVE
  To evaluate levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in CETPH, and to delineate their role in the disease pathogenesis.
  
  
  METHODS
  Plasma concentrations of TF and TFPI were evaluated in 21 CTEPH patients, in 12 patients with pulmonary arterial hypertension (PAH), in 55 APE survivors without persistent pulmonary hypertension after at least 6 months from the acute episode, and in 53 healthy volunteers (control group C). Most patients were treated with vitamin K antagonists (VKA), and some with unfractionated or low molecular weight heparin. Exclusion criteria included malignancy, inflammation, and recent operation.
  
  
  RESULTS
  Tissue factor concentration was lower in CTEPH and in post-APE patients, not stratified by anticoagulation modality, as compared to control group (p = 0.042; p = 0.011) and PAH group (p = 0.024, p = 0.014). Patients with CTEPH and post-APE on adequate VKA-anticoagulation had similar TF concentration to group C. TFPI concentration was similar in CETPH and post-APE patients irrespective of anticoagulation, and higher as compared to group C (respectively, p = 0.012; p = 0.024; p = 0.004). TFPI concentration was similar in patients with CETPH and in post-APE group, both on adequate VKA-anticoagulation when compared to group C. In the post-APE group, there was no significant difference in TFPI concentration between patients receiving adequate and subjects without anticoagulation. Group C was significantly (p = 0.000) younger than any other group, and showed correlation (r = 0.31) between age and TFPI concentration.
  
  
  CONCLUSIONS
  In CTEPH there is a high consumption of TF, leading to reduction in plasma concentration of TF and increase in TFPI. Adequate VKA-anticoagulation normalises TF and TFPI plasma concentrations, as is the case of APE survivors.
authors.affiliation: Centra Medyczne Luxmed-Medycyna Rodzinna we Wrocławiu, Wojewówdzki Szpital Specjalistyczny we Wrocławiu - Ośrodek Badawczo-Rozwojowy. martacisowska1@wp.pl.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Cisowska-Czajka
authors.forename: Mariusz P
authors.initials: MP
authors.lastname: Mazij
authors.forename: Maria H
authors.initials: MH
authors.lastname: Kotschy
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lewczuk
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000097:blood; D013925:Thromboplastin / Q000032:analysis*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D014812:Vitamin K; D013925:Thromboplastin
keywords: anticoagulation; chronic thromboembolic pulmonary hypertension (CTEPH); tissue factor (TF); tissue factor pathway inhibitor (TFPI)