Effect of platelet turnover on whole blood platelet aggregation in patients with coronary artery disease.
BACKGROUND
Previous studies have demonstrated considerable variation in the antiplatelet effect of aspirin.


OBJECTIVE
To investigate the impact of platelet turnover on the antiplatelet effect of aspirin in patients with stable coronary artery disease (CAD) and to identify determinants of platelet turnover.


METHODS
Platelet turnover was evaluated by measurements of immature platelets and thrombopoietin in 177 stable CAD patients on aspirin monotherapy, including 85 type 2 diabetics and 92 non-diabetics. Whole blood platelet aggregation was determined using the VerifyNow(®) Aspirin test and multiple electrode aggregometry (MEA, Multiplate(®) ) induced by arachidonic acid (AA) (1.0 mm), adenosine diphosphate (ADP) (10 μm) and collagen (1.0 μg mL(-1) ).


RESULTS
Immature platelet levels significantly correlated with MEA (r = 0.31-0.36, P-values < 0.0001) and the platelet activation marker sP-selectin (r = 0.19, P = 0.014). Contrary to the VerifyNow(®) test, MEA significantly correlated with variations in platelet count (r = 0.45-0.68, P-values < 0.0001). Among patients with residual platelet reactivity according to AA, there were significantly more diabetics (61% vs. 41%, P = 0.027) and higher levels of sP-selectin (77.7 ± 29 vs. 70.2 ± 25 ng mL(-1) , P = 0.070) and serum thromboxane B(2) (0.81 [0.46; 1.70] vs. 0.56 [0.31; 1.12] ng mL(-1) , P = 0.034). In a multivariate regression analysis, immature platelet levels were determined by thrombopoietin levels (P < 0.001), smoking (P = 0.020) and type 2 diabetes (P = 0.042).


CONCLUSIONS
The antiplatelet effect of aspirin was reduced in CAD patients with an increased platelet turnover. Once-daily dosing of aspirin might not suffice to adequately inhibit platelet aggregation in patients with an increased platelet turnover.
Departments ofCardiology Clinical Biochemistry, Aarhus University Hospital, Skejby, Aarhus, Denmark.
E L
EL
Grove
A M
AM
Hvas
S B
SB
Mortensen
S B
SB
Larsen
S D
SD
Kristensen
D000244:Adenosine Diphosphate; D000368:Aged; D016718:Arachidonic Acid; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003094:Collagen; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D010979:Platelet Function Tests; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013926:Thrombopoietin / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; C546937:SELP protein, human; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D013926:Thrombopoietin; D001241:Aspirin