Hemorrhagic disorders of fibrinolysis: a clinical review

Summary: Hyperfibrinolytic bleeding can be caused by a deficiency of one of the inhibitors of fibrinolysis (plasminogen activator inhibitor type 1 [PAI-1] or α2-antiplasmin [α2-AP]), or an excess of one of the activators of fibrinolysis: tissue-type plasminogen activator or urokinase-type plasminogen activator. This review focuses on the clinical implications of these disorders. The bleeding phenotype of fibrinolytic disorders is characterized by delayed bleeding after trauma, surgery and dental procedures. Bleeding in areas of high fibrinolytic activity is also common, such as menorrhagia and epistaxis. Patients with α2-AP deficiency present with the most severe bleeding episodes. Recently, it was discovered that hyperfibrinolytic disorders are associated with a high rate of obstetric complications such as miscarriage and preterm birth, especially in PAI-1 deficient patients. Hyperfibrinolytic disorders are probably underdiagnosed because of lack of knowledge and lack of accurate diagnostic tests. A substantial part of the large group of patients diagnosed as ‘bleeding of unknown origin’ could actually have a hyperfibrinolytic disorder. In the case of a high index of suspicion (i.e. because of a positive family history, recurrent bleeding or uncommon type of bleeding such as an intramedullary hematoma), further testing should not be withheld because of normal results of standard hemostatic screening assays. Timely diagnosis is important because these disorders can generally be treated well with antifibrinolytic agents.