Mechanisms underlying the morning increase in platelet aggregation: a flow cytometry study.
OBJECTIVE
Mechanisms underlying the morning increase in platelet aggregation produced by arising and assuming the upright posture were studied by examining 1) the expression on the platelet surface of activation-dependent markers; 2) platelet aggregation in whole blood; and 3) hematologic factors likely to influence aggregation.


BACKGROUND
The morning increase in thrombotic cardiovascular events has been attributed, in part, to the morning surge in platelet aggregability, but its mechanisms 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 were measured before and after arising in 17 normal volunteers. The fibrinolytic variables, tissue-type plasminogen activator, plasminogen activator inhibitor 1 and catecholamine levels were also measured.


RESULTS
On arising and standing, platelet aggregation increased by 71% (p < 0.01) and 27% (p < 0.03) in response to collagen and adenosine diphosphate, respectively. However, there was no change in any of the activation-dependent platelet surface markers. Whole-blood platelet count and 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 antigen increased (31%, p < 0.01), but there was no significant increase 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 were carefully mimicked in vitro and resulted in a 115% (p < 0.05) increase in platelet aggregation in response to adenosine diphosphate.


CONCLUSIONS
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-blood aggregation may be primarily due to the increases in catecholamine levels, platelet count and hemoconcentration.
Andrews
N P
NP
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Gralnick
H R
HR
Merryman
P
P
Vail
M
M
Quyyumi
A A
AA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016824:Antigens, Human Platelet / Q000032:analysis; D002940:Circadian Rhythm; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D005434:Flow Cytometry; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D010974:Platelet Aggregation; D010976:Platelet Count; D011187:Posture; D011516:Prothrombin / Q000032:analysis; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000032:analysis
D016824:Antigens, Human Platelet; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C045879:prothrombin fragment 1.2; D000244:Adenosine Diphosphate; D011516:Prothrombin; D003094:Collagen; D010959:Tissue Plasminogen Activator; D009638:Norepinephrine; D004837:Epinephrine