Laboratory evidence of hyperfibrinolysis in association with low plasminogen activator inhibitor type 1 activity

Low activity of plasminogen activator inhibitor type 1 (PAI-1) has been associated with bleeding complications in surgery. We earlier reported a higher prevalence of low PAI-1 activity among patients with bleeding tendency as compared with normal control individuals. The present study evaluated whether low PAI-1 activity actually is associated with markers of increased fibrinolytic activity in plasma from patients with a history of bleeding. PAI-1 activity, plasmin -antiplasmin complex (PAP) and D-dimer were analyzed in plasma samples from 424 consecutive patients referred to the Coagulation Unit for investigation of bleeding symptoms. The median PAI-1 activity was 4.0 U/ml Interquartile range (IQR), 1 - 10 U/mll, the median PAP level was 1.59 mg/I (IQR, 1.40-1.91 mg/l) and the median D-dimer level was 71 mu g/I (IQR, 46-111 mu g/l). The median PAP concentration for patients with PAI-1 less than 1.0 U/ml was 1.73 mg/I (IQR, 1.53- 2.30 mg/1), and that for PAI-1 of at least 1.0 U/ml was 1.54 mg/I (IQR, 1.36 -1.83 mg/1) (P<0.0001). There was also a significant difference between the PAP levels in patients with normal PAI-1 1-15 U/ml) versus elevated PAI-1 (>15U/ml) (P= 0.024). The level of D-dimer did not correlate with PAI-1 activity. In conclusion, the activation of plasminogen measured as PAP was higher in patients with bleeding symptoms in combination with PAI-1 activity less than 1.0 U/ml than in those with PAI-1 activity of at least 1.0 U/ml. The coagulation activity under normal conditions, as measured by D-dimer, did not differ between the two patient subsets. The results support our previous definition of low PAI-1 as activity below 1.0 U/ml. Blood Coagul Fibrinolysis 18:657660 (c) 2007 Lippincott Williams & Wilkins.