Prevention of the Liquoid-Induced Consumption Coagulopathy by the Protease Inhibitor Aprotinin

Abstract

SummaryThe protease inhibitor aprotinin reduced the incidence of the generalized Shwartzman reaction after Liquoid injection into the rabbit. This inhibitory effect is caused by the interference of aprotinin with the intravascular coagulation process (consumption coagulopathy) since decreases in fibrinogen levels after Liquoid injection were prevented. As the main anticoagulant effect of aprotinin is the inhibition of surface factor activation and as on the other hand Liquoid acts as a surface-active substance, it seems conceivable that aprotinin might prevent Liquoid-induced consumption coagulopathy by interfering with Hageman factor activation.Aprotinin did not have any effect on the incidence of hemorrhages in the lungs in Liquoid-injected animals.Furthermore, aprotinin prolonged the survival time of rabbits injected with Liquoid. This effect is not related to the action of aprotinin on the coagulation process.

Development of Glomerular Fibrinolytic Activity in the Rat

“…Deposits of fibrin were readily identifiable by specific immunofluorescence in rats after liquoid injection [20, own observation] as well as in children with hemolytic uremic syndrome. Intravascular coagulation is considered as an intermediary mechanism responsible for renal injury in both conditions [14]. GFA was augmented after liquoid injection.…”

Pathophysiology of Generalized Intravascular Coagulation

“…If the occurrence of the generalized Shwartzman reaction was inhibited by pre treating the animals with warfarin, Hageman factor activity did not decrease anymore, although there is no reason for endotoxin not to attack Hageman factor [106,162]. Furthermore, the inhibition of Hageman factor activation by lysozymes did not prevent GIC after endotoxin injection [162], whereas lysozymes inhibited GIC induced by Liquoid, indicating the primary activation of Hageman factor by Liquoid [158,160,165]. If endotoxin was injected into rabbits with an impaired intrinsic coagulation system, GIC still occurred [231].…”