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Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM\/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC\u20101 antibody (specific for activated integrin \u03b1IIb\u03b23) binding were significantly elevated in patients with MGUS <jats:italic>versus<\/jats:italic> the HCs. These markers were also elevated in SM\/MM, but not significantly. In all, 74% of MGUS and 38% of SM\/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker\u2010specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor\u2010activating peptide 6] stimulation <jats:italic>in vitro<\/jats:italic> was observed, with significantly reduced surface levels of P\u2010selectin in response to ADP in patients with MGUS. Platelet\u2010leucocyte aggregates were not altered in patients, while platelet\u2010associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM\/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.<\/jats:p>","DOI":"10.1111\/bjh.16774","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T11:50:52Z","timestamp":1591012252000},"page":"322-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance"],"prefix":"10.1111","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1072-4689","authenticated-orcid":false,"given":"Leanne R.","family":"O\u2019Sullivan","sequence":"first","affiliation":[{"name":"School of Biochemistry and Cell Biology University College Cork Cork 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