Print Email Facebook Twitter a2-Antiplasmin Enschede: Dysfunctional alpha 2-antiplasmin molecule associated with an autosomal recessive hemorrhagic disorder Title a2-Antiplasmin Enschede: Dysfunctional alpha 2-antiplasmin molecule associated with an autosomal recessive hemorrhagic disorder Author Kluft, C. Nieuwenhuis, H.K. Rijken, D.C. Groeneveld, E. Wijngaards, G. van Berkel, W. Dooijewaard, G. Sixma, J.J. Gaubius instituut TNO Publication year 1987 Abstract ??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 22.214.171.124; Plasmin, EC 126.96.36.199; Plasminogen, 9001-91-6 Subject Autosomal recessive inheritanceBleeding tendencyCase reportheredityAdolescentAntiplasminCase ReportFibrinFibrinolysisHemorrhagic DisordersHumanImmunodiffusionImmunoelectrophoresis, Two-DimensionalMaleMutationPapainPedigreePlasminPlasminogenSupport, Non-U.S. Gov't To reference this document use: http://resolver.tudelft.nl/uuid:40c1b456-25ff-4e9d-8a8a-ee4defba03a4 TNO identifier 230430 ISSN 0021-9738 Source Journal of Clinical Investigation, 80 (5), 1391-1400 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.