High Prevalence of Acquired Platelet Secretion Defects in Multiple Myeloma.

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.