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Mitchell, J. L., Khan, D., Rana, R. H., Kriek, N., Unsworth, A. J., Sage, T., Bye, A. P. 
ORCID: https://orcid.org/0000-0002-2061-2253, Laffan, M., Shapiro, S., Thakurta, A., Grech, H., Ramasamy, K. and Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352
(2023)
Multiple myeloma and its treatment contribute to increased platelet reactivity.
Platelets, 34 (1).
2264940.
ISSN 1369-1635
doi: 10.1080/09537104.2023.2264940
Abstract/Summary
Multiple myeloma (MM) and its precursor states, smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analysed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.
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| Item Type | Article |
| URI | https://reading-clone.eprints-hosting.org/id/eprint/113503 |
| Item Type | Article |
| Refereed | Yes |
| Divisions | Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology |
| Uncontrolled Keywords | Platelets, thrombosis, myeloma, IMiD, Lenalidomide |
| Publisher | Informa Healthcare |
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