Incomplete reversal of enoxaparin-induced bleeding by protamine sulfate

The neutralizing effect of protamine sulfate on enoxaparin-induced bleeding was compared in two rat models: one employing the gastric mucosa, and the other the tail skin, using a 2:1 ratio of protamine sulfate to enoxaparin on a weight basis. Whereas protamine sulfate reduced the median bleeding time (from 20 to 9.5 min) and blood loss (80%) in the gastric mucosa, and apparent 'all-or-none' response was seen in the tail skin, in agreement with a different hemostatic mechanism in the two bleeding models. In both models, protamine sulfate incompletely reversed the bleeding induced by enoxaparin.