Abstract
There is adequate preclinical data to support the differential biochemical and pharmacological behavior of the currently approved low molecular weight heparins (LMWHs) in the United States. Initial studies on the anti-Xa, anti-IIa, and U.S. Pharmacopoeial (USP) potencies have clearly demonstrated differences among these products. Furthermore, the ratios between the anti-X and anti-IIa activities vary from one product to another. THis is primarily due to the composition of each product manufactured by using different patented methods. Studies in pharmacologic animal models, using gravimetric dosages or adjusted anti-Xa dosages of the LMWHs, produce product-specific results. The pharmacokinetics and pharmacodynamics of each product also vary markedly and are not predictable on the basis of any pharmacopoeial potency designation. These agents are capable of releasing tissue factor pathway inhibitor (TFPI), an inhibitor of the coagulation process. Its release is also dependent on the type of LMWH. In the United States enoxaprin, dalteparin, and ardeparin have been approved for DVT prophylaxis. Only enoxaparin and dalteparin have been approved for the acute coronary syndrome. Recently the clinical differentiation among these LMWHs has been demonstrated in the treatment of acute coronary syndrome. Similarly, when these drugs are used at high dosages, they are expected to produce product-specific pharmacodynamic effects. It must be noted that while these drugs may be interchangeable at clinically optimized/approved dosages, these drugs are not interchangeable at equivalent anti-Xa dosages. Even at optimized dosages, the clinical provile of each drug may be different. Thus, each of the LMWHs should be considered a distinct entity and their use in a given clinical situation should be validated in proper clinical trials.