A new model to assess the haemorrhagic potential of various heparin preparations.

Abstract

In the gastric mucosa, haemostasis is hampered by the acidity and peptic activity of the gastric juice and by the fibrinolytic activity of plasmin. The hostile intragastric environment may be responsible for the unsecure haemostasis, with episodes of rebleeds often seen in gastroduodenal haemorrhage. Secondly, the haemostatic mechanisms of the gastric mucosa are largely independent of platelet aggregation and thus rely mainly on the coagulation system, making the gastric mucosa a unique model to test haemorrhagic effects of anticoagulants. Using a rat gastric chamber technique, we studied bleeding times from induced gastric mucosal lesions after intravenous administration of unfractionated and low molecular weight heparins. The bleeding times were dose-dependently prolonged by all heparins. With unfractionated heparin, significant prolongation of the bleeding times was seen already at a dose of 75 anti-Factor Xa U/kg, proving that the present model is more sensitive than previous models. The bleeding time per unit dose of both Kabi 2165 (p less than 0.05) and enoxaparin (p less than 0.001) was significantly less than that of unfractionated heparin.