Evaluating Heparin Products for Heparin-Induced Thrombocytopenia Using Surface Plasmon Resonance

Fuming Zhang, Payel Datta, Jonathan S. Dordick, Robert J. Linhardt

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)975-980
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number2
DOIs
StatePublished - Feb 2020
Externally publishedYes

Keywords

  • heparin
  • heparin-induced thrombocytopenia
  • platelet factor 4
  • surface plasmon resonance

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