title: Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.
abstract: BACKGROUND
  Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder characterized by pulmonary arterial hypertension as a consequence of organized thrombotic material in the central pulmonary arteries. Incomplete resolution of acute pulmonary emboli is believed to be pathogenically important; however, the mechanism for poor thrombus dissolution remains to be explained. We undertook this study to assess the major determinants of plasma fibrinolysis in patients with CTEPH (n = 32).
  
  
  RESULTS
  Immunological and functional levels of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH group, no between-group differences were detected in the enzymatic activities of these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in response to an experimentally induced venous occlusion. Immunoprecipitation and fibrin autography of PPP from two patients with markedly elevated basal t-PA antigen levels demonstrate that the t-PA antigen was present in PPP primarily in complex with PAI-1.
  
  
  CONCLUSIONS
  Although abnormalities of the fibrinolytic system were detected, neither a high resting plasma PAI-1 activity nor a blunted response of t-PA to venous occlusion can be invoked as an etiology for CTEPH:
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California, San Diego.
authors.forename: M A
authors.initials: MA
authors.lastname: Olman
authors.forename: J J
authors.initials: JJ
authors.lastname: Marsh
authors.forename: I M
authors.initials: IM
authors.lastname: Lang
authors.forename: K M
authors.initials: KM
authors.lastname: Moser
authors.forename: B R
authors.initials: BR
authors.lastname: Binder
authors.forename: R R
authors.initials: RR
authors.lastname: Schleef
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004691:Endarterectomy; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D007223:Infant; D015849:Plasminogen Inactivators / Q000097:blood; D013923:Thromboembolism / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator