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Thrombocytopenia in Patients Receiving Prolonged Linezolid May be Caused by Oxidative Stress

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Abstract

Background and objectives

Oxidative stress in drug-induced thrombocytopenia (TP) has been discussed. This study was carried out to assess the oxidative stress in patients with normal platelet count (NPC) and TP after linezolid (LZD) treatment and to evaluate if TP caused by LZD is associated with a reduction in antioxidation ability and an increase in lipid peroxidative product in platelets.

Methods

After LZD treatment for 20 days, 44 patients with TP and 73 patients with NPC were included in this study. Blood samples were collected on the day before medicine treatment and day 7, 14, and 20 after LZD therapy. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cholesterol as well as the activities of antioxidative enzyme were estimated. In addition, we identified 37 patients with TP caused by low-dose methotrexate (7.5–25 mg/week) therapy as a positive control group.

Results

In total, 37.60 % of cases presented with TP on the 20th day of LZD administration. Individuals with TP had significantly elevated levels of ROS and MDA, low levels of superoxide dismutase (SOD) and catalase (CAT), significantly decreased high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol levels, and increased oxidized-LDL levels in comparison to individuals with NPC. However, no significant changes in the levels of glutathione-peroxidase were found in the course of time. In all cases with LZD, significant increases in levels of ROS, MDA, and ox-LDL were found in the 20-day samples compared with their respective samples before LZD treatment. Correlation analysis revealed a positive association between platelet count and levels of SOD on day 20 and CAT on days 14 and 20 in plasma, a negative association between platelet count and level of MDA and ROS on days 14 and 20 in patients with LZD-induced TP.

Conclusions

The oxidative stress markers were increased in LZD-induced TP, suggesting that oxidative damage might be the underlying mechanism.

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Acknowledgments

This study was supported by the major national science and technology special projects for new drugs (No. 2012ZX09303004-002). We also thank all editors and reviewers for helpful suggestions that improved this manuscript.

Author Contributions

Conceived and designed the study: WR G-DH. Performed the studies: W-TL, BY, WK. Analyzed the data: W-TL. Contributed reagents/materials/analysis tools: WR G-DH, W-HL. Wrote the paper: W-HL, H-WY. Language corrections: H-WY. W-TL and G-DH contribute equally to this work.

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Authors and Affiliations

  1. Department of Pharmaceutical Care, General Hospital of People’s Liberation Army, Beijing, China

    Tian-Lin Wang, Dai-Hong Guo & Yan Bai

  2. Center of Medicine Clinical Research, General Hospital of People’s Liberation Army, 28 Fu-xing Road, Beijing, China

    Ke Wen & Rui Wang

  3. Department of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN, USA

    Wen-Yan Han

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  1. Tian-Lin Wang
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  2. Dai-Hong Guo
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  3. Yan Bai
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  4. Ke Wen
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  6. Rui Wang
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Corresponding author

Correspondence to Rui Wang.

Ethics declarations

This study was approved by the Ethics Committee of the PLA General Hospital, China, and written informed consent was obtained from all patients and volunteers.

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Wang, TL., Guo, DH., Bai, Y. et al. Thrombocytopenia in Patients Receiving Prolonged Linezolid May be Caused by Oxidative Stress. Clin Drug Investig 36, 67–75 (2016). https://doi.org/10.1007/s40261-015-0352-0

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