Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 32, Issue 1, Pages 147-U337Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.111.239392
Keywords
arterial thrombosis; platelets; thrombosis; integrins; mean platelet volume
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Funding
- National Heart, Lung and Blood Institute [R01-HL46979, R01-HL54203, R01-HL086904]
- National Institute of General Medical Sciences [GM084545]
- Gustavus and Louise Pfeiffer Research Foundation
- Donald E. and Delia B. Baxter Foundation
- American Heart Association
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Objective-The interindividual variation in platelet alpha(2)beta(1) exceeds a 2-fold variance in platelet alpha(IIb)beta(3) level. Our objective was to parse the contribution of mean platelet volume (MPV) and integrin gene alleles to this variation in large cohorts of patients with acute coronary syndrome (ACS) and normal subjects. Methods and Results-Platelet alpha(IIb)beta(3) and alpha(2)beta(1) levels were measured by flow cytometry in whole blood from 320 ACS patients and 128 normal subjects and compared with MPV, platelet count, ITGA2 rs1126643, and ITGB3 rs5918 alleles. In all subjects, a strong direct correlation was found between MPV and alpha(IIb)beta(3) level (P<0.001). Neither MPV nor alpha(IIb)beta(3) level correlated with ITGB3 rs5918 alleles. In the case of alpha(2)beta(1) level, MPV contributed modestly, whereas ITGA2 rs1126643 exerted a greater effect. An inverse correlation was found between MPV and the rs1126643 minor allele. Conclusion-MPV is the major effector of platelet alpha(IIb)beta(3) level, whereas the ITGA2 rs1126643 alleles influence alpha(2)beta(1) level more than MPV does. The rs1126643 minor allele, associated with lower MPV, likely exerts this effect via the influence of alpha(2)beta(1) on megakaryocyte maturation. Because of the hyperactivity of larger platelets, MPV is an accurate metric of risk for adverse outcome in ACS. (Arterioscler Thromb Vasc Biol. 2012;32:147-152.)
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