Impairment of the plasmin activation system in primary pulmonary hypertension: evidence for gender differences.
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.
Christ
G
G
Department of Cardiology, University of Vienna, Austria. guenter.christ@univie.ac.at
Graf
S
S
Huber-Beckmann
R
R
Zorn
G
G
Lang
I
I
Kneussi
M
M
Binder
B R
BR
Huber
K
K
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
D001779:Blood Coagulation Factors; D013917:Thrombin; D005341:Fibrinolysin