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/ml], the median PAP level was 1.59 mg/l (IQR, 1.40-1.91 mg/l) and the median D-dimer level was 71 microg/l (IQR, 46-111 microg/l). The median PAP concentration for patients with PAI-1 less than 1.0 U/ml was 1.73 mg/l (IQR, 1.53-2.30 mg/l), and that for PAI-1 of at least 1.0 U/ml was 1.54 mg/l (IQR, 1.36-1.83 mg/l) (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 (> 15 U/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.
Agren
Anna
A
Department of Hematology, Coagulation Unit, Karolinska University Hospital, Stockholm, Sweden. anna.agren@karolinska.se
Wiman
Björn
B
Schulman
Sam
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D006474:Hemorrhagic Disorders / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000172:deficiency*; D011485:Protein Binding; D012189:Retrospective Studies; D013548:Sweden; D010959:Tissue Plasminogen Activator / Q000097:blood*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin