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Discordance between the 1st and 2nd low molecular weight heparin (LMWH) standards. Implications for dosing
Author(s) -
Jeske Walter,
Cunanan Josephine,
Hoppensteadt Debra,
Walenga Jeanine M,
Iqbal Omer,
Florian Michelle,
Fareed Jawed
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a656-b
Subject(s) - potency , low molecular weight heparin , chemistry , dosing , pharmacology , mathematics , heparin , medicine , in vitro , biochemistry
The molecular weight profile and biologic activities of the 1st and 2nd LMWH standards are distinct. A systematic study was carried out to cross‐reference anti‐Xa and anti‐IIa potencies of name‐brand and commercially available generic LMWHs against these standards. Differences were observed in the slopes of the concentration‐response curves for these standards in both the anti‐Xa and anti‐IIa assays. The potencies of the generic LMWHs ranged from 76 to 119 U/mg in relation to the 1st standard and from 88 to 122 U/mg in relation to the 2nd standard. On average, the anti‐Xa potency was 8% higher when calculated with the 2nd standard. There was a wider variation among anti‐IIa potencies (1st standard range: 15‐31 U/mg; 2nd standard range: 19‐41 U/mg). On average, anti‐IIa potency was 28% higher when calculated with the 2nd standard. When used to cross‐reference commercially available LMWHs, the new standard overestimates the anti‐Xa potency by 5‐10% in comparison to the 1st standard which may lead to a reduction in dose and impact clinical efficacy. These studies demonstrate the limitations of using of the 1st and 2nd LMWH standards for evaluating the potency of LMWHs and their generic versions. Before the 2nd standard is used, it should be cross‐referenced against the 1st standard in order to consistently assign the anti‐Xa and anti‐IIa activities. This study underscores the need for developing individual standards for each of the branded products. Such designations will be particularly useful in evaluating the potential equivalence of generic versions of branded LMWHs.