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-sit u thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activatio n system are associated with the predominate affection of females. Plasma l evels of plasminogen activator inhibitor type I (PAI-1), tissue-type plasmi nogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standa rdized venous occlusion (VO) in patients with PPH (24 female, 9 male). At b aseline, 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 p ositive correlation to mean pulmonary artery pressure (mPAP), as well as no nsignificant lower t-PA activity, higher PAI-I 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, a s well as increased PAI-1 activity (p = 0.05). We hypothesize, that the obs erved presence of gender differences in the plasmin- and thrombin activatio n system in PPH leading to an antifibrinolytic/prothrombotic state might, i n part, explain the female predominant incidence of this disease.