More on: Discovery of alpha2-plasmin inhibitor and its congenital deficiency.

摘要

I read with great interest the historical sketch 'Discovery of alpha_2-plasmin inhibitor (alpha_2-PI) and its congenital deficiency' by Professor Aoki. Like Professor Aoki, I was working in the late 1960s and early 1970s on plasma inhibitors of plasmin and plasminogen activation. From 1965 until 1973, I worked in the research laboratories of Pfizer Limited with JTB Shaw on a project to find novel fibrinolytic-thrombolytic drugs. In early studies during assay development, we discovered that in the absence of serum, fibrin clots incorporating plasminogen and urokinase lyzed at rates that were only slightly affected by the concentration of anions in the clot fluid. In the presence of serum, however, the lysis times were markedly lengthened in the presence of certain anions, especially chloride ions. This effect was not seen when preformed plasmin was incorporated into plasminogen-deficient fibrin clots. We concluded that plasmin produced by the activation of plasminogen in situ in a fibrin clot was protected in some way from antiplasmins and suggested that certain ions weakened the complexes between plasminogen and fibrin and that plasmin formed in their presence would lose its immunity to antiplasmins and be inhibited in the same way as extraneous plasmin. In the presence of acetate ions, serum inhibition of activator-induced fibrinolysis was reduced. I used this information to develop a sensitive dilute blood clot lysis assay for detecting 'spontaneous' fibrinolysis in whole blood.