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A Fibrin Cross-linking Polymer Enhances Clot Formation Similar to Factor Concentrates and Tranexamic Acid in an in Vitro Model of Coagulopathy

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    A Fibrin Cross-linking Polymer Enhances Clot Formation Similar to Factor Concentrates and Tranexamic Acid in an in Vitro Model of Coagulopathy
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    † Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Avenue NE, Box 355061, Seattle, Washington 98195, United States
    ‡ Department of Medicine, Division of Emergency Medicine, University of Washington, Seattle, Washington 98195, United States
    *Phone: 206-744-8465. Fax: 206-744-4097. E-mail: [email protected]
    *Phone: 206-685-3488. E-mail: [email protected]
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    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2016, 2, 3, 403–408
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    https://doi.org/10.1021/acsbiomaterials.5b00536
    Published January 28, 2016
    Copyright © 2016 American Chemical Society
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    Abstract

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    Transfusion of blood components and factor concentrates is clinically used to replenish clotting factors and treat coagulopathy after injury when bleeding is severe. Alternatively, direct manipulation of fibrin polymerization via synthetic cross-linking agents may also improve clot formation during coagulopathic conditions as a novel way to treat coagulopathy. We recently developed a synthetic hemostatic polymer, PolySTAT, that promotes clot formation and stabilizes fibrin network structure by cross-linking fibrin monomers. In this study, we used rotational thromboelastometry (ROTEM) to monitor the effect of PolySTAT on the mechanical strength of clots during clot formation and breakdown in comparison to replacement clotting factors and antifibrinolytics under conditions of simulated trauma-induced coagulopathy (sTIC). Human recombinant activated factor VII (rFVIIa) shortened clotting onset time and accelerated clotting rate, while tranexamic acid (TXA) eliminated clot lysis and restored maximal clot firmness. In contrast, fibrinogen and PolySTAT were both able to speed up clot formation, increase maximal firmness, and inhibit clot lysis. Furthermore, PolySTAT acted synergistically with TXA and fibrinogen, enhancing their individual effects on clot formation. Thus, manipulating fibrin clot structure by physical cross-linking with a synthetic polymer has beneficial effects on clot formation and may be a viable transfusion strategy for treatment of coagulopathy.

    Copyright © 2016 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsbiomaterials.5b00536.

    • The dose-dependent relationship of rFVIIa and clotting time is further supported in graphs of each experimental replicate. Each replicate contains samples that were measured simultaneously with an hour time-lapse between replicates due to limited channels on the ROTEM machines. Changes in plasma enzymatic activity over time (that would partially account for standard deviations across different replicates) do not affect the trends observed within each replicate (PDF)

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    Cited By

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    This article is cited by 15 publications.

    1. Robert J. Lamm, Trey J. Pichon, Frederick Huyan, Xu Wang, Alexander N. Prossnitz, Karl T. Manner, Nathan J. White, Suzie H. Pun. Optimizing the Polymer Chemistry and Synthesis Method of PolySTAT, an Injectable Hemostat. ACS Biomaterials Science & Engineering 2020, 6 (12) , 7011-7020. https://doi.org/10.1021/acsbiomaterials.0c01189
    2. Mélyssa Cambronel, Kan Wongkamhaeng, Christelle Blavignac, Christiane Forestier, Jean‐Marie Nedelec, Isabelle Denry. Novel Honeycomb Nanoclay Frameworks With Hemostatic and Antibacterial Properties. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2024, 112 (9) https://doi.org/10.1002/jbm.b.35477
    3. Quanshi Guo, Yihang Ding, Lisha Yu, Zongrui Tong, Zhengwei Mao. Bioactive Hydrogels with Pro‐coagulation Effect for Hemostasis †. Chinese Journal of Chemistry 2024, 42 (1) , 87-103. https://doi.org/10.1002/cjoc.202300380
    4. Jannika Brinkmann, Hanna Malyaran, Miriam Aischa Al Enezy‐Ulbrich, Shannon Jung, Chloé Radermacher, Eva Miriam Buhl, Andrij Pich, Sabine Neuss. Assessment of Fibrin‐Based Hydrogels Containing a Fibrin‐Binding Peptide to Tune Mechanical Properties and Cell Responses. Macromolecular Materials and Engineering 2023, 4 https://doi.org/10.1002/mame.202200678
    5. Xiang-Fei Li, Pengpeng Lu, Hao-Ran Jia, Guofeng Li, Baofeng Zhu, Xing Wang, Fu-Gen Wu. Emerging materials for hemostasis. Coordination Chemistry Reviews 2023, 475 , 214823. https://doi.org/10.1016/j.ccr.2022.214823
    6. Liangyu Wang, Fan Hao, Saihua Tian, Huifeng Dong, Jun Nie, Guiping Ma. Targeting polysaccharides such as chitosan, cellulose, alginate and starch for designing hemostatic dressings. Carbohydrate Polymers 2022, 291 , 119574. https://doi.org/10.1016/j.carbpol.2022.119574
    7. Isabelle Denry, Jean‐Marie Nédélec, Julie A. Holloway. Tranexamic acid‐loaded hemostatic nanoclay microsphere frameworks. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2022, 110 (2) , 422-430. https://doi.org/10.1002/jbm.b.34918
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    9. Suvash Ghimire, Pritha Sarkar, Kasey Rigby, Aditya Maan, Santanu Mukherjee, Kaitlyn E. Crawford, Kausik Mukhopadhyay. Polymeric Materials for Hemostatic Wound Healing. Pharmaceutics 2021, 13 (12) , 2127. https://doi.org/10.3390/pharmaceutics13122127
    10. Massimo F. Cau, Amy W. Strilchuk, Christian J. Kastrup. Nanomedicines for hemorrhage control. Journal of Thrombosis and Haemostasis 2021, 19 (4) , 887-891. https://doi.org/10.1111/jth.15211
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    12. Iwan Vaughan Roberts, Deena Bukhary, Christopher Yusef Leon Valdivieso, Nicola Tirelli. Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering. Macromolecular Bioscience 2020, 20 (1) https://doi.org/10.1002/mabi.201900283
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    14. Huantong Su, Shuda Wei, Fangping Chen, Ruihua Cui, Changsheng Liu. Tranexamic acid-loaded starch hemostatic microspheres. RSC Advances 2019, 9 (11) , 6245-6253. https://doi.org/10.1039/C8RA06662K
    15. N. A. Pulina, V. Yu. Kozhukhar, A. S. Kuznetsov, A. E. Rubtsov, A. V. Starkova. Synthesis and search for compounds with hemostatic activity in the series of 4-(het)aryl-4-oxobut-2-enoic acid derivatives. Russian Chemical Bulletin 2017, 66 (8) , 1497-1502. https://doi.org/10.1007/s11172-017-1914-5
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    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2016, 2, 3, 403–408
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsbiomaterials.5b00536
    Published January 28, 2016
    Copyright © 2016 American Chemical Society
    Request reuse permissions

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