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Microparticles from splenectomized β-thalassemia/HbE patients play roles on procoagulant activities with thrombotic potential

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Abstract

Thromboembolic events including cerebral thrombosis, deep vein thrombosis, and pulmonary embolism are major complications in β-thalassemia. Damaged red blood cells and chronic platelet activation in splenectomized β-thalassemia/HbE patients were associated with increased microparticles (MPs) releases into blood circulation. MPs are small membrane vesicles, which play important roles on coagulation. However, the role of MP in thalassemia is poorly understood. In this study, the effects of splenectomized-MPs on platelet activation and aggregation were investigated. The results showed that isolated MPs from fresh platelet-free plasma of patients and normal subjects directly induce platelet activation, platelet aggregation, and platelet-neutrophil aggregation in a dose-dependent manner. Interestingly, MPs obtained from splenectomized patients are more efficient in induction of platelet activation (P-selectin+) when compared to MPs from normal subjects (P < 0.05), tenfold lower than pathophysiological level, at 1:0.1 platelet MP ratio. Co-incubation of splenectomized-MPs with either normal-, non-splenectomized- or splenectomized-platelets at 1:10 platelet MP ratio increased platelet activation up to 5.1 ± 2.2, 5.6 ± 3.7, and 9.5 ± 3.0%, respectively, when normalized with individual baseline. These findings suggest that splenectomized patients were proned to be activated by MPs, and splenectomized-MPs could play an important role on chronic platelet activation and aggregation, leading to thrombus formation in β-thalassemia/HbE patients.

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Abbreviations

MPs:

microparticles

PPP:

platelet-poor plasma

PRP:

platelet-rich plasma

PS:

phosphatidylserine

PSGL-1:

P-selectin glycoprotein ligand-1

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Acknowledgements

This work was supported by Faculty of Science, Mahidol University; Faculty of Science and Faculty of Medicine Ramathibodi Hospital, Mahidol University; Mahidol University Research Grants; Office of the Higher Education Commission and Mahidol University under the National Research University Initiative; Thailand Research Fund (TRF) (IRG5780009); The TRF Distinguished Research Professor Grant (DPG5980001); The Royal Golden Jubilee PhD Program of TRF; and Research Chair Grant, National Science and Technology Development Agency, Thailand. PK was supported under the Royal Golden Jubilee PhD Program of TRF.

Authors’ contributions

PK, KPh, and WK performed the experiments and analyzed the data. EN and NPM contributed to the concept of the study and interpretation. AK and SF contributed to the concept of the study and specimen collection. SS contributed to the concept of the study, design the experiments, the analysis of the data, and drafting the manuscript. KPa and PC were the principal investigator and take primary responsibility for the concept and design of the project, the analysis of the data, and drafting the manuscript. All authors reviewed and approved the final version to be published.

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Authors and Affiliations

  1. Department of Immunology and Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Pran-Nok, Bangkok-Noi, Bangkok, 10170, Thailand

    Phatchanat Klaihmon, Egarit Noulsri & Kovit Pattanapanyasat

  2. Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand

    Kunwadee Phongpao, Wasinee Kheansaard, Suthat Fucharoen & Saovaros Svasti

  3. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand

    Kunwadee Phongpao & Saovaros Svasti

  4. Molecular Medicine Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand

    Wasinee Kheansaard & Saovaros Svasti

  5. Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Archrob Khuhapinant

  6. Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand

    Noppawan Phumala Morales

  7. Department of Pathobiology, Faculty of Science, Mahidol University, 272 RamaVI Rd., Ratchathewi, Bangkok, 10400, Thailand

    Pornthip Chaichompoo

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  1. Phatchanat Klaihmon
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Corresponding authors

Correspondence to Kovit Pattanapanyasat or Pornthip Chaichompoo.

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Funding

This work was supported by Faculty of Science, Mahidol University; Faculty of Science and Faculty of Medicine Ramathibodi Hospital, Mahidol University; Mahidol University Research Grants; Office of the Higher Education Commission and Mahidol University under the National Research University Initiative; Thailand Research Fund (TRF) (IRG5780009); The TRF Distinguished Research Professor Grant (DPG5980001); The Royal Golden Jubilee Program of TRF; and Research Chair Grant, National Science and Technology Development Agency, Thailand.

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The authors declare that they have no conflict of interest.

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Additional information

Phatchanat Klaihmon and Kunwadee Phongpao contributed equally to this work.

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Klaihmon, P., Phongpao, K., Kheansaard, W. et al. Microparticles from splenectomized β-thalassemia/HbE patients play roles on procoagulant activities with thrombotic potential. Ann Hematol 96, 189–198 (2017). https://doi.org/10.1007/s00277-016-2885-6

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  • DOI: https://doi.org/10.1007/s00277-016-2885-6

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