Ex vivo activity of heparin is not predictive of blood loss after neutralization by protamine.

To study whether the ex vivo activity of heparin and Fraxiparin correlates to and predicts the extent of blood loss induced by the heparins (pre- and post neutralization by protamine), a rat tail transection model and a rabbit ear bleeding model were used. In the rat model heparin (2 mg/kg i.v.) significantly prolonged the bleeding time, while this dose of Fraxiparin had no effect. In the rabbit ear blood loss model, heparin (2 mg/kg i.v.) produced significant increases in blood loss while Fraxiparin (2 mg/kg i.v.) produced approximately 30% of the blood loss induced by heparin. Equigravimetric protamine reduced the heparin-induced blood loss by approximately 50%, however, significant blood loss, thrombin time and Heptest activity remained. Heparin and Fraxiparin (3 mg/kg s.c.) did not cause any increased bleeding. While, all activities of heparin were completely neutralized by protamine, the Heptest activity of Fraxiparin was resistant to neutralization. The ex vivo activity of heparins after neutralization by protamine does not correlate to the extent of blood loss which suggests it may not be necessary to neutralize all ex vivo activities of the heparins to baseline values to be assured that blood loss is reversed.