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Role of platelets in thrombin generation amongst patients with non-transfusion-dependent thalassaemia

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Abstract

Non-transfusion-dependent thalassaemia (NTDT) is associated with a hypercoagulable state with thrombotic risk highest after splenectomy. Various mechanisms have been proposed. Although an antiplatelet agent is commonly recommended as thromboprophylaxis in NTDT, the role of platelets contributing to this hypercoagulable state is not well-defined. This study aims to evaluate the role of platelets contributing to hypercoagulability in NTDT patients using thrombin generation (TG). Platelet-rich (PRP) and platelet-poor plasma (PPP) were collected from NTDT patients (n = 30) and normal controls (n = 20) for TG measurement and compared. Controls had higher endogenous thrombin potential (ETP) in PPP (1204.97 nM.min vs 911.62 nM.min, p < 0.001) and PRP (1424.23 nM.min vs 983.99 nM.min, p < 0.001) than patients. Patients’ mean normalized ETP ratio [{PRP ETP (patient)/PPP ETP (patient)}/{mean PPP ETP (controls)/mean PPP ETP (controls)}], demonstrated that the presence of platelet does not alter ETP (mean ratio 0.97, 95% CI 0.93–1.02, equivalence defined as 10%). Types of thalassaemia, splenectomy, and severity of liver iron overload did not significantly influence patients’ ETP in PPP and PRP by multivariate analysis. Platelets did not increase the TG potential of NTDT patients. Instead of being hypercoagulable, our NTDT patients were hypocoagulable by ETP measurement, although this could not be conclusively demonstrated to correlate with their iron overloading state giving rise to reduced synthesis of coagulation factors. The guideline recommendations for thromboprophylaxis with antiplatelet agents in similar NTDT patients should be re-examined.

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Acknowledgements

The authors are very grateful to all the study participants and Xiao Zhang for her help with the co-ordination of study subjects.

Funding

This study was funded by the Singapore General Hospital Research Grant.

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Authors and Affiliations

  1. Department of Haematology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore

    Chuen Wen Tan, Wan Hui Wong, Hartirathpal Kaur, Lai Heng Lee, Heng Joo Ng & Ai Leen Ang

  2. Department of Haematology, Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan, Brunei

    Roserahayu Idros

  3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Yiong Huak Chan

  4. Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore

    Alvin Ren Kwang Tng

Authors
  1. Chuen Wen Tan
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  2. Wan Hui Wong
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  3. Roserahayu Idros
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  4. Yiong Huak Chan
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  5. Hartirathpal Kaur
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  6. Alvin Ren Kwang Tng
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  7. Lai Heng Lee
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  8. Heng Joo Ng
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  9. Ai Leen Ang
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Correspondence to Chuen Wen Tan.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of our institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Tan, C.W., Wong, W.H., Idros, R. et al. Role of platelets in thrombin generation amongst patients with non-transfusion-dependent thalassaemia. Ann Hematol 98, 861–868 (2019). https://doi.org/10.1007/s00277-018-3579-z

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  • DOI: https://doi.org/10.1007/s00277-018-3579-z

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