Platelet turnover in stable coronary artery disease - influence of thrombopoietin and low-grade inflammation.
BACKGROUND
Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD). The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown.


OBJECTIVE
To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency.


METHODS
We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio) were determined using automated flow cytometry (Sysmex XE-2100). Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6.


RESULTS
We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61-0.99, p<0.0001). Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = -0.17--0.25, p<0.0001). Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03) and in smokers (p = 0.003). Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03) and thrombopoietin (r = 0.16, p<0.001). Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02).


CONCLUSIONS
In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a substantial impact on platelet turnover parameters.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Sanne Bøjet
SB
Larsen
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Erik Lerkevang
EL
Grove
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark ; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
Anne-Mette
AM
Hvas
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark ; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
Steen Dalby
SD
Kristensen
D000367:Age Factors; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000473:pathology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D063847:Mean Platelet Volume; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000473:pathology*; D010976:Platelet Count; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000473:pathology*; D012737:Sex Factors; D012907:Smoking; D013926:Thrombopoietin / Q000097:blood*
C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein; D013926:Thrombopoietin