Discriminatory potential of platelet function reference ranges in cardiovascular disease

Introduction Cardiovascular diseases are characterized by altered platelet activity. To distinguish between physiological and pathological platelet activity, it is essential to establish reference ranges of standardized platelet (re)activity parameters in the population, which was a major aim of this study. Furthermore, the discriminative ability of values outside these reference ranges was assessed for various cardiovascular diseases.

Method A reference group (n=329; 51% women; age: 35-85 years) was defined in a representative cohort study after exclusion of cardiovascular-related diseases and platelet function-interfering medications. Reference values for platelet function parameters were set at the 5th/95th percentiles. Multivariable linear regression was applied to assess age and sex dependence, and to identify cardiovascular determinants of platelet function parameters measured by flow cytometry, light transmission aggregometry, PFA-200, and calibrated automated thrombinography. In the total cohort with platelet function data (n=789), the prevalence ratio of coronary artery disease (CAD), myocardial infarction (MI), history of stroke, atrial fibrillation (AF), chronic heart failure (CHF), and venous thromboembolism (VTE) was estimated in relation to values outside the platelet function reference ranges by robust Poisson regression.

Results The percentage of CD63+ platelets was higher in men (median:2.60%, IQR:1.20/5.26%) than women (1.90%, 0.70/3.60%), which both decreased with age. Collagen/ADP-induced occlusion time decreased (β [log-transformed DV]=-0.03, p=0.044) with age and platelet aggregability, spontaneously and in response to collagen, increased with age (β [log-transformed dependent variable, DV]=0.094, p=0.0031; β=1.58, p=0.029). Tissue factor-triggered endogenous thrombin potential (ETP) decreased (β=-33.8, p=0.021) and lag time increased (β=0.348, p=0.0046) with age. Arterial hypertension, obesity and active smoking were independent determinants of age, sex and other risk factor of in vivo platelet activation as well as platelet aggregation and thrombin generation in vitro. Increased prevalence of CAD, MI, AF, CHF, and VTE was observed for values outside of reference limits for platelet adhesion (von Willebrand factor dependent), aggregation and coagulation parameters. In addition, history of stroke and AF were more prevalent with values exceeding the reference range for CD63+ and CD62P+ platelets, respectively.

Conclusion Platelet function test values, which exceed or fall below population-based reference ranges may predict increased prevalence of different cardiovascular diseases.

Publikationsverlauf

Artikel online veröffentlicht:
20. Februar 2023