OC 26.5 - Thyroid hormones and analogues promote the acute release of platelets from megakaryocytes: from blood donor biology to the production of platelets in vitro

Sunday, July 10, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, ICC Capital Suite Room 10&11

Presentation Format: In-Person

Presenting Author(s)

Holly R. Foster, PhD

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom

Co-Author(s)

NH

Nina Herbert

Senior Research Project Lead/Nurse
NHS Blood and Transplant/University of Cambridge
Cambridge, England, United Kingdom
AW

Amie K. Waller

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
CD

Christian A Di Buduo

Research Associate
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Pavia, Lombardia, Italy
JF

Juan Fang

Senior Research Scientist
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
AS

Anna Schmidt

Research Technician
Versiti Blood Research Insitiute/Medical College of Wisconsin
Milwaukee, Wisconsin, United States
DH

Daniel Howard

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
MT

Momal Taimoor

Research Assistant
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
TM

Thomas Moreau

Head of Research and Development
bit.bio
Cambridge, England, United Kingdom
AM

Annett Meuller

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
AE

Amanda L. Evans

Research Associate
University of Cambridge
Cambridge, England, United Kingdom
Ratnashree Biswas, MBBS MD

Postdoctoral Fellow
Versiti Blood Research Institute
Milwaukee, Wisconsin, United States
Ernest Turro, PhD

Associate Professor
Icahn School of Medicine at Mount Sinai
New York, New York, United States
RF

Roman Fischer

Associate Professor and Head of Discovery Proteomic Facility
Nuffield Department of Medicine/Univeristy of Oxford
Oxford, England, United Kingdom
David A. Wilcox, PhD

Associate Professor
Medical College of Wisconsin
MIlwaukee, Wisconsin, United States
KH

Karin M. Hoffmeister, MD

Director, Professor
Versiti Translational Glycomics Center
Milwaukee, Wisconsin, United States
Alessandra Balduini, MD

MD, PhD
University of Pavia, Pavia, Italy
Pavía, Lombardia, Italy
Cedric Ghevaert, MD PhD

Professor of Transfusion Medicine
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre
Cambridge, England, United Kingdom

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.