Potency Adjustment of Unfractionated Heparins to Harmonize the USP and WHO Standardization. Impact on Anticoagulant Practice in the US

Abstract

To harmonize the potency of US heparin (UFH) supplies with the WHO standard, the USP has mandated use of a revised procedure resulting in a 10–13% reduction of anticoagulant potency. To assess the impact of 10% potency adjustment, stock solutions of UFH were prepared to represent a 10% decrease (90 U/ml), no change (100 U/ml) and a 10% increase (110 U/ml). Differences were evaluated in the surgical and interventional range (1–5 U/ml) using the ACT and in the therapeutic range (0–1.0 U/ml) using plasma clotting assays. Protamine titration studies were conducted in both studies. Thrombin generation studies were conducted at lower levels. Rabbit models of stasis thrombosis and ear bleeding were used to determine the impact on antithrombotic and hemorrhagic activities. Differences in the ACT were only noted at concentrations >1.0 U/ml. No difference in protamine neutralization profile was noted. Supplementation to normal plasma did not result in differences in the PT, APTT, Heptest, thrombin time, anti‐IIa and anti‐Xa activities. Some differences were noted utilizing a thrombin generation assay. These studies suggest that a 10% change in heparin potency may not impact the anticoagulant practice in the therapeutic or prophylactic range. Closer monitoring may be needed in specialized populations and in those patients requiring surgical and prophylactic anticoagulation where higher concentrations of UFH are reached.