title: Impairment of the plasmin activation system in primary pulmonary hypertension: evidence for gender differences.
abstract: Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.
authors.affiliation: Department of Cardiology, University of Vienna, Austria. guenter.christ@univie.ac.at
authors.forename: G
authors.initials: G
authors.lastname: Christ
authors.forename: S
authors.initials: S
authors.lastname: Graf
authors.forename: R
authors.initials: R
authors.lastname: Huber-Beckmann
authors.forename: G
authors.initials: G
authors.lastname: Zorn
authors.forename: I
authors.initials: I
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Kneussi
authors.forename: B R
authors.initials: BR
authors.lastname: Binder
authors.forename: K
authors.initials: K
authors.lastname: Huber
mesh_terms: D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000378:metabolism; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D001779:Blood Coagulation Factors; D013917:Thrombin; D005341:Fibrinolysin