We appreciate the comments of Drs Hughes and Gonzalez. However, it seems that they have misunderstood the mechanism of action of LMWH and made an incorrect conclusion in their letter. Increasing the dose of heparin compensates for the reduced bioavailability of antithrombin III, not the reduced bioavailability of heparin. Therefore, even though LMWH have a more predictable bioavailability than unfractionated heparin, the anticoagulant effect of the LMWH is dependent on the bioavailability of antithrombin III. In fact, because LMWH have a greater concentration of the pentasaccharide chain responsible for antithrombin III activation and fewer high-molecular-weight fractions (responsible for the minor direct heparin antithrombotic effect), they are even more critically dependent on the presence of antithrombin III for their effect. To state this another way, if there is inadequate antithrombin III, both unfractionated heparin and LMWH are ineffective.
We understand that different LMWH preparations have different ratios of anti-IIa