Effect of platelet turnover on whole blood platelet aggregation in patients with coronary artery disease

J Thromb Haemost. 2011 Jan;9(1):185-91. doi: 10.1111/j.1538-7836.2010.04115.x.

Abstract

Background: Previous studies have demonstrated considerable variation in the antiplatelet effect of aspirin.

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate
  • Aged
  • Arachidonic Acid
  • Aspirin / therapeutic use*
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Case-Control Studies
  • Chi-Square Distribution
  • Collagen
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy*
  • Denmark
  • Diabetes Mellitus, Type 2 / blood
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Count
  • Platelet Function Tests
  • Registries
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Thrombopoietin / blood
  • Thromboxane B2 / blood

Substances

  • Biomarkers
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • SELP protein, human
  • Arachidonic Acid
  • Thromboxane B2
  • Adenosine Diphosphate
  • Collagen
  • Thrombopoietin
  • Aspirin