Imbalance of plasminogen activator inhibitor type-1 (PAI-1) and tissue plasminogen activator (t-PA) activity in patients with Noonan syndrome

J Pediatr Hematol Oncol. 2010 Oct;32(7):532-6. doi: 10.1097/MPH.0b013e3181e0d152.


Background: Patients with Noonan syndrome have been reported to have an increased incidence of bleeding with trauma and surgery. Although various abnormalities of hemostasis have been described in reported series, there has been no consistent abnormality described and none have investigated fibrinolytic pathways.

Methods: Fibrinolytic parameters including tissue plasminogen activator (t-PA; activity and antigen), plasminogen activator inhibitor type-1 (PAI-1; activity and antigen), plasminogen (activity and antigen), thrombin-antithrombin complex, prothrombin time (PT), and activated partial thromboplastin time where studied in 12 patients with Noonan syndrome (total of 15 data sets). PT and activated partial thromboplastin time were performed locally whereas the fibrinolytic parameters were performed in a single national reference laboratory. Individual results were compared with published age-appropriate norms and the mean values of the study patients were compared with the midpoint of normal range for each component measured. The ratio of PAI-1/t-PA activity was calculated for each set of results and compared with a "normal" value calculated from the midpoint normal range value for each component.

Results: Patients with Noonan syndrome consistently demonstrated an elevation of t-PA activity in relationship to PAI-1 activity and a decreased PAI-1/t-PA ratio (P<0.01 for each comparison).

Conclusions: Patients with Noonan syndrome seem to have an imbalance in fibrinolytic components favoring fibrinolysis. This may be an important contributor to the bleeding noted in these patients.

MeSH terms

  • Adolescent
  • Antithrombin III / metabolism
  • Child
  • Child, Preschool
  • Female
  • Fibrinolysis / physiology*
  • Hemorrhage / blood*
  • Hemostasis / physiology
  • Humans
  • Male
  • Noonan Syndrome / blood*
  • Partial Thromboplastin Time
  • Peptide Hydrolases / metabolism
  • Plasminogen / metabolism
  • Plasminogen Activator Inhibitor 1 / blood*
  • Prothrombin Time
  • Tissue Plasminogen Activator / blood*
  • Young Adult


  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • antithrombin III-protease complex
  • Antithrombin III
  • Plasminogen
  • Peptide Hydrolases
  • Tissue Plasminogen Activator