Summary
Phenylbutazone, oxyphenbutazone, and sulfinpyrazone were equally effective at the
dosage of 100 mg/kg (per os) in inhibiting thrombin- and ADP-induced platelet aggregation
in hyperlipemic rats, and in preventing the development of thrombosis initiated by
the intravenous injection of an endotoxin. Despite a slight anticoagulant effect of
these substances, their antithrombotic activity appears to be due mostly to inhibition
of platelet aggregation.
Thrombosis in hyperlipemic rats could also be prevented by a dicoumarol derivative,
acenocoumarin, which only inhibits coagulation. Therefore, both platelet aggregation
and fibrin formation appear to be essential for the occurrence of large thrombi under
these conditions. Nevertheless, although acenocoumarin has no direct effect on platelet
aggregation, it could indirectly affect this phenomenon by blocking the formation
of thrombin, which is suspected of being the agent responsible for initiating thrombosis
in hyperlipemic rats.
Low doses of phenylbutazone and acenocoumarin, in condition, which when given alone
were ineffective in inhibiting thrombosis, could decrease the severity of thrombosis
by 33%. The substance GP45840, when added in vitro to platelet-rich plasma as well as given per os to hyperlipemic rats, was no more
effective than sulfinpyrazone in inhibiting platelet aggregation. Nevertheless, this
substance was significantly more efficient in reducing thrombosis than was sulfinpyrazone,
apparently through some additional anticoagulant activity. The results of these experiments
suggest that it could be beneficial to affect both coagulation and platelet aggregation
in order to satisfactorily prevent thrombosis.
