Antithrombin III Glasgow: a variant with increased heparin affinity and reduced ability to inactivate thrombin, associated with familial thrombosis.
A functional antithrombin III (AT III) deficiency has been identified in two generations of a family with a high incidence of thrombosis. The deficiency presented as approximately 50% reduction in heparin cofactor activity compared to its antigen concentration. No abnormality was detected by crossed immunoelectrophoresis in the presence or absence of heparin. Plasma from the propositus was precipitated with dextran sulphate, applied to heparin-Sepharose and the AT III stepwise eluted with NaCl. The AT III had a reduced ability to inactivate thrombin, when this was monitored by substrate hydrolysis or by SDS polyacrylamide gel electrophoresis. Its mobility was normal by the latter technique using 10-20% gradient gels under reducing and non-reducing conditions. AT III from the patient was reapplied to heparin-Sepharose and eluted with a NaCl gradient. An active pool eluted in the same NaCl concentration range used to purify normal AT III, while predominantly inactive AT III eluted at higher NaCl concentrations. It is concluded that this variant, designated AT III Glasgow, has increased affinity for heparin but reduced ability to inactivate thrombin.
Lane
D A
DA
Department of Haematology, Charing Cross and Westminster Medical School, Hammersmith, London.
Lowe
G D
GD
Flynn
A
A
Thompson
E
E
Ireland
H
H
Erdjument
H
H
D000990:Antithrombin III / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D058833:Antithrombin Proteins; D000991:Antithrombins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013917:Thrombin / Q000037:antagonists & inhibitors; D013924:Thrombophlebitis / Q000097:blood / Q000235:genetics*
D058833:Antithrombin Proteins; D000991:Antithrombins; C094336:antithrombin Glasgow; C054089:antithrombin III Glasgow; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin