title: Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesis.
abstract: BACKGROUND
  Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking.
  
  
  OBJECTIVE
  To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population.
  
  
  METHODS
  In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls.
  
  
  RESULTS
  The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL(-1), was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77 and 2.75; 1.39-5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding tendency.
  
  
  CONCLUSIONS
  Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations.
authors.affiliation: Department of Hematology, Coagulation Unit, King Gustaf V Research Institute, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Agren
authors.forename: B
authors.initials: B
authors.lastname: Wiman
authors.forename: V
authors.initials: V
authors.lastname: Stiller
authors.forename: P
authors.initials: P
authors.lastname: Lindmarker
authors.forename: M
authors.initials: M
authors.lastname: Sten-Linder
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.forename: J
authors.initials: J
authors.lastname: Odeberg
authors.forename: S
authors.initials: S
authors.lastname: Schulman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006474:Hemorrhagic Disorders / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency*; D015995:Prevalence; D011485:Protein Binding; D012307:Risk Factors; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator