a2-Antiplasmin Enschede: Dysfunctional alpha 2-antiplasmin molecule associated with an autosomal recessive hemorrhagic disorder

??2-Antiplasmin (??2-AP) is a major fibrinolysis inhibitor, whose complete, congenital absence has been found to be associated with a distinct hemorrhagic diathesis. We studied a 15-yr-old male with a hemorrhagic diathesis after trauma from early childhood on. This bleeding tendency was associated with a minimal ??2-AP level recorded functionally in the immediate plasmin inhibition test: ???4% of normal. However, a normal plasma concentration of ??2-AP antigen (83%) was found. His sister (5 yr old) showed similar results (2 and 92%). In their family, eight heterozygotes could be identified by half-normal activity results and normal antigen concentrations. The inheritance pattern is autosomal recessive. On analysis, the ??2-AP of the propositus was homogeneous in all respects tested, suggesting a homozygous defect. We designated the abnormal ??2-AP as ??2-AP Enschede. ??2-AP Enschede showed the following characteristics: (a) complete immunological identity with normal ??2-AP; (b) normal molecular weight (sodium dodecyl sulfate-polyacrylamide gel electrophoresis); (c) normal ??-electrophoretic mobility; (d) presence in plasma of both molecular forms excluding and excessive conversion to the less reactive non-plasminogen-binding form; (e) quantitatively normal binding to lys-plasminogen and to immobilized plasminogen kringle 1-3; and (f) normal Factor XIII-mediated binding to fibrin. Functional abnormalities were found in: (i) no inhibition of amidolytic activities of plasmin and trypsin, even on prolonged incubation; (ii) no formation of plasmin-antiplasmin complexes in plasma with plasmin added in excess; and (iii) no inhibition of fibrinolysis by fibrin-bound ??2-AP. In the heterozygotes, the presence of abnormal ??2-AP did not interfere with several functions of the residual normal ??2-AP. One-dimensional peptide mapping showed an abnormal pattern of papain digestion. We conclude that in this family, abnormal antiplasmin molecules, defective in plasmin inhibition but with normal plasminogen-binding properties, have been inherited. The residual plasminogen-binding properties do not protect against a hemorrhagic diathesis.Chemicals/CAS: antiplasmin, 9049-68-7; Antiplasmin; Fibrin, 9001-31-4; Papain, EC 3.4.22.2; Plasmin, EC 3.4.21.7; Plasminogen, 9001-91-6