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CC BY-NC-ND 4.0 · Hamostaseologie
DOI: 10.1055/a-2418-5664
Original Article

High Prevalence of Acquired Platelet Secretion Defects in Multiple Myeloma

Frauke Swieringa
1   Synapse Research Institute, Maastricht, The Netherlands
,
Yaqiu Sang
1   Synapse Research Institute, Maastricht, The Netherlands
2   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Jasper A. Remijn
3   Department of Clinical Chemistry, Meander Medical Center, Amersfoort, The Netherlands
,
Rob Fijnheer
4   Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands
,
Suzanne J. A. Korporaal
5   Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
,
Rolf T. Urbanus
6   Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
,
Dana Huskens
1   Synapse Research Institute, Maastricht, The Netherlands
,
Joke Konings
1   Synapse Research Institute, Maastricht, The Netherlands
,
Li Li
1   Synapse Research Institute, Maastricht, The Netherlands
,
Bas de Laat
1   Synapse Research Institute, Maastricht, The Netherlands
,
Mark Roest
1   Synapse Research Institute, Maastricht, The Netherlands
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Abstract

Thrombocytopenia at admission predicts mortality in multiple myeloma (MM) and might link to disease progression. Although thrombocytopenia is known to be associated with MM, a possible thrombopathy is clinically less known. We conducted a case–control study comparing platelet responses of MM patients to controls via flow cytometry, integrin αIIbβ3 activation and P-selectin exposure, and a bioluminescent assay, ATP release. No difference was found at baseline, but upon platelet stimulation, MM patients had decreased αIIbβ3 activation, partly impaired P-selectin exposure, and reduced δ-granule (ATP) secretion. Aspirin treatment in patients did not account for these diminished platelet responses. In total, 29% of patients had thrombocytopenia, while 60% had decreased αIIbβ3 activation and 67% had reduced platelet secretion capacity. Importantly, as secretion capacity was corrected for platelet count, granule release per platelet was reduced in patients versus controls. Of 6 patients with thrombocytopenia 4 displayed a thrombopathy, while for 15 patients with normal count, 64% had reduced αIIbβ3 activation and 73% had reduced platelet secretion capacity. Of all patients, 10% had thrombocytopenia combined with reduced αIIbβ3 activation plus low secretion capacity (one patient showed no qualitative or quantitative platelet defect). Our data suggest that beyond the known thrombocytopenia, MM patients also have reduced platelet function, which could reflect impaired platelet vitality. Combined measurement of platelet count and function, especially secretion capacity, gives a more comprehensive view of platelet phenotype than count alone. Large prospective follow-up studies are needed to confirm the importance of the acquired platelet secretion defect on the prognosis of MM patients.

Keywords

multiple myeloma - thrombocytopenia - platelet secretion

Authors' Contributions

J.K. and M.R. designed the research; R.F. recruited the patients; Y.S., L.L., and M.R. performed experiments and collected the data; S.J.A.K. provided the reaction kits for flow cytometric analysis; Y.S., D.H., F.S., and M.R. performed data analysis; Y.S. and M.R. wrote the original manuscript; Y.S., M.R., J.A.R., R.F., K.S., S.J.A.K., R.T.U., D.H., F.S., J.K., L.L., and B.d-L. revised the manuscript; J.K., M.R., and J.A.R. supervised the study.


Supplementary Material



Publication History

Received: 03 July 2024

Accepted: 18 September 2024

Article published online:
11 February 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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