Evaluating heparin products for heparin-induced thrombocytopenia using surface plasmon resonance

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Authors
Zhang, Fuming
Datta, Payel
Dordick, Jonathan S.
Linhardt, Robert J.
Issue Date
2020-02-01
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Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Heparin-induced thrombocytopenia (HIT) is an adverse immunological disorder caused by antibodies to platelet factor 4 (PF4)-heparin complexes. The analysis of HIT potential for different heparin and heparin-related products is important prior to their clinical application. Here, we report a rapid method for the evaluation of HIT potential of various heparin and heparin-related compounds using surface plasmon resonance (SPR). Solution competition between surface-immobilized heparin and soluble unfractionated heparin, low molecular weight heparin (LMWH), or ultra-LMWH binding to PF4 was performed using SPR to measure the half maximal inhibitory concentration (IC50) of different heparin products. The IC50 values of different unfractionated heparin active pharmaceutical ingredients (APIs) varied from 0.38 to 0.6 μg/mL and the IC50 values of different LMWH APIs ranged from 2.4 to 2.9 μg/mL. The IC50 of Arixtra® (a synthetic pentasaccharide ultra-LMWH) was not measurable even at very high concentrations. These differences in IC50 values for different heparin products suggest a quantitative means for evaluating the HIT potential of various heparins and heparin-related products.
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Journal of Pharmaceutical Sciences,109, 975-980
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Full Citation
Evaluating heparin products for heparin-induced thrombocytopenia using surface plasmon resonance, F. Zhang, P. Datta, J. S. Dordick, R. J. Linhardt, Journal of Pharmaceutical Sciences,109, 975-980, 2020.
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15206017
223549
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