CONGENITAL DEFICIENCY OF ALPHA-2-PLASMIN INHIBITOR ASSOCIATED WITH SEVERE HEMORRHAGIC TENDENCY

α2-Plasmin inhibitor (α2PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. The authors report here a case of complete deficiency of α2PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extremely rapid and was complete in 4-8 hr. The concentration of plasma protease inhibitors, including α2-macroglobulin, antithrombin III, α1-antitrypsin, and ClINH, were all normal. The concentration of α2-PI in the patient's plasma, assayed by immunological methods, was < 0.1 mg/100 ml (normal concentration, 6.1 ± 0.88 mg/100 ml [mean ± SE]) and functional assays showed a complete deficiency of α2PI. Addition of purified α2PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, 4 siblings, and 4 other members of this family were asymptomatic, but the titers of α2PI in their plasmas were κ 50% of normal pooled plasma. There were 3 consanguineous marriages in this family, and the α2PI deficiency appears to have been inherited as an autosomal recessive trait. The authors speculate that α2PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of α2PI in hemostasis.