MECHANISMS UNDERLYING THE MORNING INCREASE IN PLATELET-AGGREGATION - A FLOW-CYTOMETRY STUDY

Objectives. Mechanisms underlying the morning increase in platelet agg regation produced by arising and assuming the upright posture were stu died by examining 1) the expression on the platelet surface of activat ion dependent markers; 2) platelet aggregation in whole blood; and 3) hematologic factors likely to influence aggregation. Background. The m orning increase in thrombotic cardiovascular events has been attribute d, in part, to the morning surge in platelet aggregability, but its me chanisms are poorly understood. Methods. Expression of seven platelet surface antigens (including P-selectin, activated GPIIb-IIIa and GPIb- IX), whole-blood platelet aggregation, platelet count and hematocrit w ere measured before and after arising in 17 normal volunteers. The fib rinolytic variables, tissue-type plasminogen activator, plasminogen ac tivator inhibitor I and catecholamine levels were also measured. Resul ts. On arising and standing, platelet aggregation increased by 71% (p < 0.01) and 27% (p < 0.03) in response to collagen and adenosine dipho sphate, respectively. However, there was no change in any of the activ ation-dependent platelet surface markers. Whole-blood platelet count a nd hematocrit increased by 15% and 7% (both p < 0.0001), respectively. Norepinephrine and epinephrine levels increased by 189% (p < 0.0001) and 130% (p < 0.01), respectively. Tissue-type plasminogen activator a ntigen increased (31%, p < 0.01), but there was no significant increas e in plasminogen activator inhibitor 1, suggesting an overall increase in fibrinolysis on standing. Prothrombin fragment 1.2 increased by 28 % (p < 0.02), indicating a small increase in thrombin generation. The increases in hematocrit and platelet count that occurred on standing w ere carefully mimicked in vitro and resulted in a 115% (p < 0.05) incr ease in platelet aggregation in response to adenosine diphosphate. Con clusions. These data demonstrate that the morning increase in platelet aggregation is not accompanied by expression of activation-dependent platelet surface receptors and suggest that the increase in whole bloo d aggregation may be primarily due to the increases in catecholamine l evels, platelet count and hemoconcentration. (C) 1996 by the American College of Cardiology