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Transient blood thinning during extracorporeal blood purification via the inactivation of coagulation factors by hydrogel microspheres

Nature Biomedical Engineering volume 5, pages 1143–1156 (2021)Cite this article

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Abstract

During extracorporeal blood purification, anticoagulants are administered to prevent thrombogenesis. However, haemorrhagic complications owing to near-complete inactivation of blood coagulation and delayed recovery of haemostasis pose serious risks to patients. Here, we show in vitro and in beagle dogs that hydrogel microspheres that adsorb the coagulation factors VIII, IX and XI provide transient blood thinning when placed in the extracorporeal circuit before blood purification. The microspheres inhibited the activities of the coagulation factors by levels (~8–30%) similar to those occurring in mild haemophilia. On its reintroduction into the animal, the purified pseudo-haemophilic blood favoured faster recovery of haemostasis. The transient blood-thinning strategy may increase the safety of clinical blood-purification procedures.

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Fig. 1: Design and evaluation of the biocompatibility of the spheres in vitro.
Fig. 2: Design and evaluation of the blood-thinning properties of the spheres in vitro.
Fig. 3: Establishment of the pseudo-haemophilia model and its safety in vivo.
Fig. 4: Efficacy of the pseudo-haemophilia model in vivo.
Fig. 5: Practical application of the pseudo-haemophilia model in haemodialysis.

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Data availability

The main data supporting the results in this study are available within the paper and its SupplementaryInformation. The raw and analysed datasets generated during the study are too large to be publicly shared; however, they are available for research purposes from the corresponding authors upon reasonable request.

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Acknowledgements

This work was financially sponsored by the State Key Research Development Programme of China (grant numbers 2016YFC1103000 and 2018YFC1106400), the National Natural Science Foundation of China (grant numbers 51433007, 51673125, 51773127, 51873115, 51803131 and 51803134) and the Science and Technology Program of Sichuan Province (2017SZ0011 and 2019YJ0132). We also gratefully acknowledge the help of H. Wang, of the Analytical and Testing Center at Sichuan University, for the SEM micrographs. Moreover, we thank our laboratory members for their generous help. J.N.K. acknowledges funding from the Canadian Institutes of Health Research and Natural Sciences and Engineering Council of Canada (NSERC). J.N.K. is a recipient of a Michael Smith Foundation for Health Research Career Scholar Award.

Author information

Author notes

  1. These authors contributed equally: Xin Song, Haifeng Ji, Yupei Li.

Authors and Affiliations

  1. College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, China

    Xin Song, Haifeng Ji, Qiang Wei, Weifeng Zhao & Changsheng Zhao

  2. Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China

    Yupei Li, Yuqin Xiong & Baihai Su

  3. Sichuan University–the Hong Kong Polytechnic University Institute for Disaster Management and Reconstruction, Chengdu, China

    Yupei Li & Baihai Su

  4. Department of Ultrasound, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China

    Li Qiu

  5. Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Peking Union Medical College, Chengdu, China

    Rui Zhong

  6. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China

    Meng Tian

  7. Department of Pathology and Laboratory Medicine, Center for Blood Research and Life Science Institute, University of British Columbia, Vancouver, British Columbia, Canada

    Jayachandran N. Kizhakkedathu

  8. Department of Cellular Biophysics, Max Planck Institute for Medical Research, Heidelberg, Heidelberg, Germany

    Qiang Wei

  9. Department of Biophysical Chemistry, University of Heidelberg, Heidelberg, Germany

    Qiang Wei

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Contributions

X.S., H.J., W.Z. and C.Z. conceived the early pseudo-haemophilia model concepts and/or designed the experiments. X.S. and H.J. performed initial development work and analysed the data. X.S. and H.J. prepared, characterized and performed the in vitro biocompatibility evaluation of the microspheres. Y.L. and Y.X. designed and conducted the animal experiments. R.Z. and M.T. designed and conducted the studies for the coagulation factors. L.Q., J.N.K., B.S. and Q.W. provided conceptual advice and technical support. X.S., Y.L. and W.Z. drafted the manuscript. W.Z. and C.Z. supervised the study and revised the paper. All authors gave approval to the final version of the manuscript.

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Correspondence to Weifeng Zhao or Changsheng Zhao.

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Peer review information Nature Biomedical Engineering thanks the anonymous reviewers for their contribution to the peer review of this work.

Supplementary information

Supplementary Information

Supplementary methods, figures, tables, scheme, video captions and references.

Reporting Summary

Supplementary Video 1

Simulated pseudo-haemophilia model.

Supplementary Video 2

Treatment and recovery process in a transfused dog.

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Song, X., Ji, H., Li, Y. et al. Transient blood thinning during extracorporeal blood purification via the inactivation of coagulation factors by hydrogel microspheres. Nat Biomed Eng 5, 1143–1156 (2021). https://doi.org/10.1038/s41551-020-00673-x

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