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Artificial cerebrospinal fluid restores aspirin-inhibited physiological hemostasis through recovery of platelet aggregation function

  • Original Article - Neurosurgery General
  • Published:
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Abstract

Background

Optimal hemostasis provides safety and reliability during neurosurgery which improves surgical outcomes. Previously, artificial cerebrospinal fluid (aCSF) and its component sodium bicarbonate were found to facilitate physiological hemostasis by amplifying platelet aggregation. This study aimed to verify whether aCSF amplifies platelet-dependent hemostasis in the presence of antiplatelet agents.

Methods

We prepared platelet-rich plasma (PRP) or washed platelets using aspirin (acetylsalicylic acid, (ASA)) or normal saline (NS). We evaluated samples treated with a commercially available aCSF solution or NS for amplification of aggregation, activation of integrin αIIbβ3, phosphatidylserine (PS) exposure, P-selectin (CD62P) expression, and formation of microparticles (MPs). We assessed the effect of aCSF on in vivo hemostasis in the presence of ASA by measuring the tail bleeding time in ASA-or NS-injected C57BL/6 N mice.

Results

Compared with NS, aCSF amplified ASA-inhibited platelet aggregation by recovering platelet activation including PS exposure, MP release, CD62P expression, and integrin αIIbβ3 activation. When using washed platelets, aCSF almost completely counteracted the inhibition of platelet aggregation by ASA. Prolonged bleeding time from the amputated tail of ASA-injected mice was significantly shortened by the treatment with aCSF compared to NS. Sodium bicarbonate also directly amplified ASA-inhibited platelet aggregation.

Conclusions

aCSF and sodium bicarbonate facilitate physiological hemostasis through the recovery of inhibited platelet aggregation even in the presence of ASA. The utilization of aCSF in the operative field may be advantageous for facilitating hemostasis in patients with impaired platelet function and contribute to improving outcomes of neurosurgery.

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Data availability

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.

Abbreviations

ACD:

Acid–citrate–dextrose

aCSF:

Artificial cerebrospinal fluid

ADP:

Adenosine diphosphate

ASA:

Acetylsalicylic acid

CD62P:

P-selectin

Cy5:

Cyanine-5

DAG:

Diacylglycerol

FITC:

Fluorescein isothiocyanate

GP:

Glycoprotein

IP3:

Inositol 1,4,5-trisphosphate

mAb:

Monoclonal antibody

MAPK:

Mitogen-activated protein kinase

MP:

Microparticle

NS:

Normal saline

PE:

Phycoerythrin

PRP:

Platelet-rich plasma

PS:

Phosphatidylserine

RT:

Room temperature

SD:

Standard deviation

TXA2 :

Thromboxane A2

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Acknowledgements

We are grateful to Akemi Matsubara, PhD, for statistical consultation, and to Editage (www.editage.com) for English language editing.

Funding

This work was supported by JSPS KAKENHI (grant numbers JP18K08587 and JP21K08608), and Kumamoto Health Science University special fellowship (grant number 2018-D-03).

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Author notes

  1. Ryosuke Suzuki and Yukinori Kozuma contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan

    Ryosuke Suzuki, Nobuyuki Shimizu & Tetsuya Yamamoto

  2. Department of Medical Technology, Faculty of Health Science, Kumamoto Health Science University, Kumamoto, Kumamoto, Japan

    Yukinori Kozuma, Kano Tanabe, Ippei Noboruo, Hohomi Arao & Tatsuya Kawaguchi

  3. Division of Medical Sciences, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Yukinori Kozuma & Chisako Inoue

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  1. Ryosuke Suzuki
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Contributions

YK and TY contributed to the conception and design of this study. YK, CI, KT, IN, and HA acquired and analyzed the data. YK and RS interpreted the data. RS and YK wrote the draft of this article, and TY contributed to the revision. All authors contributed to the study and approved the manuscript as submitted.

Corresponding author

Correspondence to Tetsuya Yamamoto.

Ethics declarations

Ethical approval

This study was approved by the ethics committee of the University of Tsukuba (approval number: 795) and Kumamoto Health Science University (approval number: 18055).

Informed consent

The volunteers included in this study provided written informed consent for using their samples.

Conflict of interest

The authors declare no competing interests.

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Suzuki, R., Kozuma, Y., Inoue, C. et al. Artificial cerebrospinal fluid restores aspirin-inhibited physiological hemostasis through recovery of platelet aggregation function. Acta Neurochir 165, 1269–1276 (2023). https://doi.org/10.1007/s00701-022-05471-9

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  • DOI: https://doi.org/10.1007/s00701-022-05471-9

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