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

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

Kluft, C.
Nieuwenhuis, H.K.
Rijken, D.C.
Groeneveld, E.
Wijngaards, G.
van Berkel, W.
Dooijewaard, G.
Sixma, J.J.
Gaubius instituut TNO

1987

??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

Autosomal recessive inheritance
Bleeding tendency
Case report
heredity
Adolescent
Antiplasmin
Case Report
Fibrin
Fibrinolysis
Hemorrhagic Disorders
Human
Immunodiffusion
Immunoelectrophoresis, Two-Dimensional
Male
Mutation
Papain
Pedigree
Plasmin
Plasminogen
Support, Non-U.S. Gov't

http://resolver.tudelft.nl/uuid:40c1b456-25ff-4e9d-8a8a-ee4defba03a4

230430

0021-9738

Journal of Clinical Investigation, 80 (5), 1391-1400

article