[Diagnosis and management of bleeding disorders caused by hyperfibrinolysis (designated intractable disease No. 347 in Japan)].

Hyperfibrinolysis-related bleeding is well recognized in conditions such as the acute phase of trauma, disseminated intravascular coagulation with hyperfibrinolysis, and acute promyelocytic leukemia. In contrast, whether primary hyperfibrinolysis can directly cause bleeding in the absence of an underlying disorder has not been sufficiently investigated, largely due to the lack of an established disease concept and the limited availability of reliable functional assays. Congenital deficiencies of individual fibrinolysis inhibitors-such as plasminogen activator inhibitor-1 (PAI-1) deficiency, α2-plasmin inhibitor (α2-PI) deficiency, and thrombomodulin (TM) disorders leading to impaired activation of thrombin-activatable fibrinolysis inhibitor (TAFI)-are extremely rare but are known to result in severe bleeding manifestations. Based on functional assessment assays for these conditions, we have proposed a novel disease entity, "bleeding disorders caused by hyperfibrinolysis," and established diagnostic criteria. This entity was designated in Japan as an intractable disease (No. 347), effective April 2025. This review outlines the clinical significance and diagnostic framework of this disorder and highlights the potential contribution of fibrinolytic dysfunction to bleeding disorder of unknown cause (BDUC).