Fibrinolytic states in a patient with congenital deficiency of alpha 2- plasmin inhibitor

Abstract

The fibrinolytic system of a patient with congenital deficiency of α2-proteinase (plasmin) inhibitor (α2PI) was studied. The patient’s whole blood clot formed in vitro was lysed rapidly in several hours on incubation. This accelerated in vitro fibrinolysis was suppressed by an addition of purified α2PI. The degree of suppression was proportional to the amount of α2PI added. In spite of the accelerated in vitro fibrinolysis, the increases of fibrinogen/fibrin-related antigen and fragment A (the earliest plasmin-catalyzed degradation product of fibrinogen) were not detected when the blood was mixed with plasmin inhibitors immediately after drawing blood. It was also revealed by sodium dodecylsulfate (SDS) gel electrophoresis that fibrinogen structure was not altered and plasminogen was in a native form. These results suggested that there was no increased in vivo fibrinogenolysis. When the patient’s citrated plasma was incubated in vitro, no progressive degradation of fibrinogen was observed in SDS gel electrophoresis in spite of the accelerated conversion of native Glu-plasminogen to modified Lys-plasminogen in the patient’s plasma. The conversion was most likely catalyzed by a trace amount of plasmin spontaneously generated during the incubation. When the patient’s plasma was clotted by recalcification, the fibrin formed was rapidly lysed. This in vitro fibrinolytic activity seems to be dependent on plasminogen activator activity in plasma, since the incubation of plasma, which decreases plasma plasminogen activator activity, resulted in the decrease of the fibrinolytic activity. With an addition of a small amount of urokinase, fibrinolysis was extensive, but there was still a very low degree of fibrinogenolysis. These results suggest that α2PI is effective in inhibiting fibrinolysis, but other protease inhibitors in plasma such as α2-macroglobulin are ineffective in inhibiting fibrinolysis, although they are effective in inhibiting plasmin in the plasma milieu thereby preventing fibrinogenolysis. Administration of tranexamic acid to the patient corrected not only the patient’s abnormal fibrinolytic system but also the hemorrhagic tendency.