Abstract Number: OC 26.5
Meeting: ISTH 2022 Congress
Background: Many improvements have been made over the past decade in the safety and quality of platelet units intended for transfusion but significant problems still remain. Often there is no alternative for severely ill patients but to be given allogenic platelets which have very limited efficacy and uncertain immunomodulatory responses and so there is a critical need for alternative treatments. Unfortunately, our current knowledge of thrombopoiesis is limited and the mediators that are directly involved remain elusive.
Aims: To elucidate soluble factors in the blood that promote platelet formation and can be used as therapeutic treatments or to upscale in vitro platelet production for transfucion purposes.
Methods: 19 plateletpheresis donors who regularly donate we recruited to analysis the dynamics of platelet recovery post acute loss of platelets. Full blood counts were performed on various timepoints before and after donation to identify the most relevant timepoints to analyse further. Metabolomic, proteomic and cytokine/chemokine/growth factor analyses were performed on the plasma/serum of these donors to identify differentially expressed analytes in these relevant timepoints compared to baseline levels. These analystes were screened in platelet production assays to identify novel targets.
Results: Using metabolomics and proteomics screening methods, thyroid hormones have been identified as potent mediators of platelet production. Triiodothyronine (T3) as well as thyroid hormone analogues, GC-1 (Sobetirome), KB2115 (Eprotirome) and MGL-3196 showed a significant effect on platelet production, as well as proplatelet formation in vitro in both primary derived- and iPSC derived-megakaryocytes. These platelets that are produced under the influence of thyroid hormones are functionally active, showing degranulation (P-selectin exposure) and incorporation into thrombi.
Conclusion(s): We have identified for the first time that thyroid hormones directly promote platelet production which offers very interesting therapeutic opportunities.
To cite this abstract in AMA style:Foster H, Herbert N, Waller A, Di Buduo C, Fang J, Schmidt A, Howard D, Taimoor M, Moreau T, Meuller A, Evans A, Biswas R, Turro E, Fischer R, Wilcox D, Hoffmeister K, Balduini A, Ghevaert C. Thyroid hormones and analogues promote the acute release of platelets from megakaryocytes: from blood donor biology to the production of platelets in vitro [abstract]. https://abstracts.isth.org/abstract/thyroid-hormones-and-analogues-promote-the-acute-release-of-platelets-from-megakaryocytes-from-blood-donor-biology-to-the-production-of-platelets-in-vitro/. Accessed November 30, 2023.
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