Monitoring unfractionated heparin therapy: relationship between eight anti-Xa assays and a protamine titration assay

Several studies have demonstrated that heparin assays, such as anti-activated factor X (anti-Xa) assays, can be successfully substituted for activated partial thromboplastin time for heparin dosage monitoring. A number of different assays are available and the relationship between results with different techniques is largely unknown. The aim of the present study was to assess the relationship between heparin assays by protamine titration and anti-Xa assays. Samples were collected from 43 patients receiving unfractionated heparin (UFH). In each sample, the heparin level was determined using a protamine titration assay and eight commercially available anti-Xa assays. The mean heparin level by protamine titration was 0.31 U/ml. Mean anti-Xa activity results ranged from 0.40 to 0.42 IU/ml for the three clotting-based assays, and from 0.32 to 0.40 IU/ml for five chromogenic assays. Thus mean results of different anti-Xa assays varied by up to 30%. The range of anti-Xa activity equivalent, on average, to 0.2-0.4 U/ml by protamine titration, considered to be the therapeutic range, was approximately 0.25-0.5 IU/ml, depending on the assay. The relationship between results of clotting and chromogenic methods was similar irrespective of whether or not warfarin-induced prolongation of international normalized ratios was present.