VPB0575 - USP Standardized Mixtures of Bovine, Ovine and Porcine Heparin Demonstrate Comparable Biologic Effects to Referenced Single Sourced Heparins and May be Interchangeable

Background: Unfractionated heparin (UFH) is the first line anticoagulant for the management of medical indications. Bovine and ovine mucosal sources represent alternate material to the commonly used porcine mucosa for production of UFH. Standardized heparins from various sources can be blended and their potency can be adjusted to exhibit comparable effects as the single sourced UFH.

Aims: The purpose of this study is to evaluate the pharmacologic profile of the blended heparin and compare these activities to that of the single sourced porcine, ovine and bovine heparins.

Methods: Clot based assays were used to study the anticoagulant effects of the heparins. The amidolytic anti-Xa assay was used to assess the inhibitory effects of these heparins on these proteases. Protamine sulfate (PS) neutralization studies were performed to evaluate the reversal of anticoagulant effects in the heparins.

Results: The aPTT assay showed that at final concentrations of 5 ug/ml and 2.5 ug/ml porcine heparin significantly prolonged the aPTT compared to ovine, bovine, and blended heparins. The potency adjusted heparins demonstrated comparable aPTT values at all concentrations (U/ml) (Figure 1). The anti-Xa assay showed that at all final concentrations between 10 ug/ml and 0.625 ug/ml porcine, ovine, and blended heparins produced significantly stronger Xa inhibition than bovine heparin. The potency adjusted heparins demonstrated comparable anti-Xa inhibition at all concentrations (U/ml) (Figure 2). The protamine sulfate neutralization studies demonstrated complete neutralization at all concentrations for all the potency adjusted heparins in the aPTT and anti-Xa assays.

Conclusion(s): These studies support the hypothesis that a blended heparin product from bovine, ovine, and porcine tissue, when standardized in USP unit-equivalent proportions, exhibits a comparable anticoagulant profile to the single species heparins. These findings suggest that there is a potential for development of an alternate heparin to stabilize supply chain of this important anticoagulant and warrant clinical validation.