329
&agr;2-PLASMIN INHIBITOR
DEFICIENCY
SIR,-Dr Koie and colleagues (Dec. 23/30, p. 1334) describe the first case of x2 plasmin inhibitor (a2-r.t.) deficiency. x,-n.t. is believed to be the most potent and most rapidly functioning plasmin inhibitor in human plasma. Of special interest was their observation that, despite a substantially shortened whole-blood clot-lysis time, the level of fibrinogen and its degradation products in the patient’s blood were normal. Koie et al. ascribe this to the presence of other plasmin inhibitors, which "are usually potent enough to prevent in-vivo fibrinogenolysis, while xz P.I. is important for the protection of local hxmostatic plugs". This conclusion fails to explain why the other inhibitors were ineffective in inhibiting whole-blood clot
lvsis.
We would like to offer another explanation, based on our observations on the differences in the mechanism of fibrinolysis and fibrinogenolysis. We have shown that fibrinogen degradation, both during in-vitro incubation and in-vivo after cuff occlusion’ or exerciser is prevented by a potent inhibitor of plasminogen activator (antiactivator). Accordingly, it is the formation of antiactivator-activator complexes which prevent the conversion of plasminogen to plasmin in blood. Antiplasmins are not involved at this stage. However, as soon as fibrin is formed, the antiactivator-activator complex is dissociated and conversion of plasminogen to plasmin takes place. The subsequent rate of lysis of fibrin is dependent on the concentration of antiplasmins in blood, as illustrated by Koie’s findings. The importance of a specific antiactivator in preventing fibrinogenolysis is shown by the results of an experiment in which clotted and unclotted plasma were incubated with human vascular activator (from cadaver limbs), urokinase, streptokinase, and plasmin. Plasmin caused comparable degradation of fibrin and fibrinogen, whereas the activators did not. In the presence of vascular activator, no fibrinogen degradation occurred, illustrating the specificity of the antiactivator for this particular activator. The rapid fibrinolysis without fibrinogenolysis observed by Koie et al. in ’-
&agr;2-PLASMIN INHIBITOR
DEFICIENCY
SIR,-Dr Koie and colleagues (Dec. 23/30, p. 1334) describe the first case of x2 plasmin inhibitor (a2-r.t.) deficiency. x,-n.t. is believed to be the most potent and most rapidly functioning plasmin inhibitor in human plasma. Of special interest was their observation that, despite a substantially shortened whole-blood clot-lysis time, the level of fibrinogen and its degradation products in the patient’s blood were normal. Koie et al. ascribe this to the presence of other plasmin inhibitors, which "are usually potent enough to prevent in-vivo fibrinogenolysis, while xz P.I. is important for the protection of local hxmostatic plugs". This conclusion fails to explain why the other inhibitors were ineffective in inhibiting whole-blood clot
lvsis.
We would like to offer another explanation, based on our observations on the differences in the mechanism of fibrinolysis and fibrinogenolysis. We have shown that fibrinogen degradation, both during in-vitro incubation and in-vivo after cuff occlusion’ or exerciser is prevented by a potent inhibitor of plasminogen activator (antiactivator). Accordingly, it is the formation of antiactivator-activator complexes which prevent the conversion of plasminogen to plasmin in blood. Antiplasmins are not involved at this stage. However, as soon as fibrin is formed, the antiactivator-activator complex is dissociated and conversion of plasminogen to plasmin takes place. The subsequent rate of lysis of fibrin is dependent on the concentration of antiplasmins in blood, as illustrated by Koie’s findings. The importance of a specific antiactivator in preventing fibrinogenolysis is shown by the results of an experiment in which clotted and unclotted plasma were incubated with human vascular activator (from cadaver limbs), urokinase, streptokinase, and plasmin. Plasmin caused comparable degradation of fibrin and fibrinogen, whereas the activators did not. In the presence of vascular activator, no fibrinogen degradation occurred, illustrating the specificity of the antiactivator for this particular activator. The rapid fibrinolysis without fibrinogenolysis observed by Koie et al. in ’-
