Clinical Features and Treatment of Hereditary and Acquired Plasmin Inhibitor Deficiency

Objective: This review reports on diagnosis, clinical features, and treatment of hereditary and acquired deficiency of plasmin inhibitor. Data Sources: We considered the international literature published since 1978, when the first case of hereditary plasmin inhibitor deficiency had been described. Selection Criteria: The studies reporting on clinical symptoms, prophylaxis, and treatment of bleeding have been completely analyzed. Results: At least 10 homozygous and 40 heterozygous cases of hereditary plasmin inhibitor deficiency have been described so far. Homozygous patients present with a severe hemorrhagic diathesis. Heterozygous patients have only a mild or no bleeding tendency. Bleeding in hereditary plasmin inhibitor deficiency can be effectively treated with antifibrinolytic agents such as tranexamic acid or epsilon aminocaproic acid. Patients with acquired plasmin inhibitor deficiency suffer from underlying diseases accompanied by complex impairment of hemostasis and fibrinolysis. There is no evidence from controlled studies that acquired plasmin inhibitor deficiency alone causes bleeding or crucially aggravates a bleeding tendency. In these patients, aprotinin should be used as an antifibrinolytic instead of tranexamic or epsilon aminocaproic acid, when indicated as a consequence of bleeding and hyperfibrinogenolysis. Controlled studies dealing with the efficacy of the administration of fresh frozen plasma and/or solvent/detergent (S/D)-treated human plasma to patients with complex disorders of hemostasis and fibrinolysis are underway. Conclusions: Hereditary plasmin inhibitor deficiency is a very rare disorder. Bleeding can successfully be managed by antifibrinolytics. Acquired plasmin inhibitor deficiency is a concomitant of complex impairment of hemostasis and fibrinolysis. Antifibrinolytic therapy is indicated when bleeding occurs as a consequence of hyperfibrinogenolysis. In these cases, aprotinin should be preferred. Controlled studies are underway to examine the efficacy of plasmin inhibitor replacement using fresh frozen plasma or S/D-treated plasma.