Comparative Study on the Anticoagulant Effects of Low Molecular Weight Heparins as Measured by Whole Blood Act, Anti-Xa and a Newly Developed Prothrombinase Induced Clotting Time (PiCT) Assay.

Low Molecular Weight Heparins (LMWHs) are currently developed for anticoagulation in various intravenous indications such as DVT treatment and percutaneous interventions (PCI). Traditionally, these drugs are administered in anti-Xa units. The purpose of this study was to compare the relative levels of anticoagulation produced by different LMWHs in whole blood ACT (Hemochron), an amidolytic anti-Xa method and a plasma-based global anticoagulant assay, the PiCT test (Pentapharm, Basel, Switzerland). Various LMWHs such as dalteparin, enoxaparin, reviparin and a synthetic pentasaccharide were supplemented to freshly drawn native blood samples to simulate patient samples containing 1 U/ml anti-Xa levels. Three generic versions of enoxaparin were also included in this study. In addition to the ACT measurement in whole blood, citrated plasma samples were also tested for APTT, Heptest, PiCT, amidolytic anti-Xa and IIa activities, and protease generation assays. All agents produced assay-based effects on different tests, which were not proportional to the adjusted anti-Xa activity. Correlation of the ACT data resulted in a good relationship with PiCT for the commercially available branded products(r²=0.97). ACT and Heptest (r²=0.51), ACT and anti-Xa (r²<0.3), ACT and anti-IIa (r²= 0.93). The correlation of PiCT and Heptest was (r²=0.73) better than ACT and Heptest. However, the generic versions of enoxaparin did not provide similar results. PiCT and Heptest also gave the good correlation. These results clearly suggest that for the global anticoagulant actions of LMWHs, anti-Xa measurements are of limited value and should not be used to asses the anticoagulant efficacy of LMWHs in PCI and other surgical conditions. These differences may be more obvious in the generic versions of LMWHs, which are apparently produced using pharmacopeial specifications. Thus, it is important to include a clot-based method in the cross referencing and standardization of LMWHs.