Key result
The specific catalytic activity for thrombin inactivation and potency to inhibit prothrombin conversion did not vary significantly between enoxaparin fractions when adjusted for active chain length.
Why the study?
Does the molecular weight of enoxaparin fractions affect their anticoagulant activity in plasma?
Does the molecular weight of enoxaparin fractions affect their anticoagulant activity in plasma?
The anticoagulant activity of enoxaparin fractions is determined by the proportion of material with high affinity to antithrombin III and critical chain length, rather than the molecular weight itself.
Normalized enoxaparin anticoagulant activity is independent of molecular weight; leaves open clinical impact of size fractionation in humans.
A low molecular weight heparin (enoxaparin, mean molecular weight approximately 4,400) was separated by gel chromatography into eight different fractions with a narrow distribution around the following mean molecular weights: 1,800, 2,400, 2,900, 4,200, 6,200, 8,600, 9,800 and 11,000. We compared the influence of enoxaparin on the generation of thrombin in plasma to that of the eight fractions. We determined: a) the % of material with high affinity to antithrombin III (HAM) and the % of HAM above the critical chain length necessary to allow for thrombin inhibition (ACLM), b) the specific catalytic activity on the decay of endogenous thrombin, and c) the inhibition of over-all thrombin formation in the extrinsic and the intrinsic pathway. From b and c we calculated the inhibition of prothrombin conversion in these pathways. We found that a) there is a gradual decrease of the HAM fraction with decreasing molecular weight; b) the specific catalytic activity for the inactivation of thrombin does not vary significantly between the fractions when expressed in terms of ACLM; c) the potency to inhibit prothrombin conversion does not vary significantly between the fractions when expressed in terms of HAM.
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Bendetowicz et al. (1992) studied this question. Enoxaparin fractions of varying molecular weights vs. Unfractionated enoxaparin was evaluated on Influence on the generation of thrombin in plasma. The specific catalytic activity for thrombin inactivation and potency to inhibit prothrombin conversion did not vary significantly between enoxaparin fractions when adjusted for active chain length.
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