On the relationship between molecular mass and anticoagulant activity in a low molecular weight heparin (enoxaparin).
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.
Bendetowicz
A V
AV
Department of Biochemistry, Rijksuniversiteit Limburg, Maastricht, The Netherlands.
Pacaud
E
E
Béguin
S
S
Uzan
A
A
Hemker
H C
HC
D000990:Antithrombin III / Q000737:chemistry; D005453:Fluorescence; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
D006495:Heparin, Low-Molecular-Weight; D000990:Antithrombin III; D013925:Thromboplastin; D013917:Thrombin