Premium
Impact of Contaminant Heterogeneity on Anticoagulation and Adverse Reactions Associated with Recalled Heparin
Author(s) -
Fareed Jawed,
Hoppensteadt Debra,
Jeske Walter,
Adiguzal Cafer,
Iqbal Omer,
Walenga Jeanine M.
Publication year - 2009
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.23.1_supplement.569.9
Subject(s) - dermatan sulfate , heparin , protamine sulfate , chemistry , protamine , contamination , chondroitin sulfate , low molecular weight heparin , chromatography , anticoagulant , neutralization , sulfate , ion chromatography , pharmacology , biochemistry , heparan sulfate , glycosaminoglycan , immunology , medicine , organic chemistry , biology , ecology , antibody
It has been assumed that different batches of contaminated heparin contained similar forms of oversulfated chondroitin sulfate (OSCS). Contaminants were isolated from four batches of UFH and two batches of LMWH by digestion of heparin followed by alcohol precipitation and ion‐exchange chromatography. Biologic activity was measured in terms of anticoagulant activity, thrombin generation inhibition, protamine/PF4 neutralization, and interaction with AT and HCII. The contaminated UFHs had different anti‐Xa:anti‐IIa ratios (0.93‐1.24) and amount of heparinase resistant material (14‐30%) and two contained significant amounts of dermatan sulfate. Isolated contaminants exhibited distinct PF4 and protamine neutralization profiles. LMWHs had comparable molecular weights and biologic actions, but differed in heparinase‐1 digestion profile. The molecular weight of the LMWH contaminant was lower (12.8 vs. 14.1‐16.8 kDa) and exhibited differences in thrombin generation inhibition. The contaminants isolated from heparin and LMWH had potencies of 28‐46 and 38‐46 USP U/mg, respectively. Contaminants isolated from recalled batches of heparin are heterogenous. Moreover, the contaminants obtained form LMWHs may exhibit additional structural and biologic differences. The variations observed in the adverse reactions with recalled heparins may be due to compositional variations in the contaminants.