Polymerisation Defect of Fibrinogen London

Abstract

In the present study further work has been carried out on fibrinogen that has been isolated from a patient with a coagulation defect tentatively designated fibrinogen London. The dysfibrinogenemia was characterised by normal polypeptide chains on SDS gel electrophoresis, normal release of fibrinopeptide A and a delayed polymerisation of fibrin monomers. The polymerisation defect was pH and ionic strength dependent and partially corrected by protamine sulphate and Ca++ ions. Studies on the NH2 and COOH terminal polymerisation domains were carried out using insolubilised fibrin monomers prepared from patient and normal fibrinogen (Kudryk et al, Thromb. Res, 9,25. 1976). High MW fragment D, prepared by plasmin digestion of normal fibrinogen, bound to both normal and patient fibrin monomer and was eluted with 8M urea indicating no gross malfunction of the NH2 terminal polymerisation domain. Also purified fibrinogens from normal and patient plasma a bound to normal fibrin monomer sepharose, suggesting that the COOH terminal domain is capable of binding to the NH2 terminal domain of normal fibrin. These results suggest that the polymerisation defect of fibrinogen London is different in character to that of fibrinogen Detroit, where the NH2 terminal domain does not bind to the normal COOH terminal domain.