Four cases of bleeding diathesis in children due to congenital plasminogenactivator inhibitor-1 deficiency

Congenital plasminogen activator inhibitor-1 (PAI-1) deficiency is an extre mely rare disorder characterized by a bleeding diathesis that begins in chi ldhood due to hyperfibrinolysis as a result of decreased PAI-1 activity. We now present 4 unrelated pediatric cases of congenital PAI-1 deficiency. Al l 4 patients had a history of recurrent episodes of subcutaneous bleeding b eginning in early childhood. These episodes were characterized by abnormal prolonged bleeding after trauma, tooth extraction, and surgical procedures, as well as by rebleeding following initial hemostasis. The 2 female patien ts both had symptoms compatible with hypermenorrhea. The family history was positive in 2 of the 4 patients. Hemostatic screening studies in all 4 pat ients revealed no abnormalities. Testing for factor XIII antigen, von Wille brand factor antigen, ristocetin cofactor activity, alpha(2)-plasmin inhibi tor (alpha 2PI) activity, and plasminogen activity was normal. The euglobul in lysis times were shortened in all cases as compared with those in normal control subjects. None of the patients had elevated tissue plasminogen act ivator (tPA) antigen levels, but PAI activity was markedly decreased in all cases. Three of the patients also had reduced revels of PAI-1 antigen. The re tended to be a reduction in tPA-PAI-1 complex in all cases. In addition, 2 patients had elevated PIC (plasmin-alpha 2PI complex). Tourniquet tests were performed in 2 patients, with no appreciable rise in PAI-1. activity o r PAI-1 antigen levels. The administration of tranexamic acid clearly impro ved hemorrhagic symptoms in these patients. We considered PAI-1 deficiency to be the likely etiology of the congenital bleeding diatheses in these 4 c ases. Copyright (C) 2000 S . Karger AG, Basel.