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Population-based reference ranges of platelet function tests and their discriminative ability for cardiovascular disease

1Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 2Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, mainz, Rheinland-Pfalz, Germany, 3Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 4Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 52 Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; 3 German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; 4 Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 69, 55131, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 62 Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 74 Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 69, 55131, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 85 Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the University of Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 96 Department of Ophthalmology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 10Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, mainz, Rheinland-Pfalz, Germany, 11Center for Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 12University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany

Abstract Number: PB0894

Meeting: ISTH 2022 Congress

Theme: Platelets and Megakaryocytes » Platelet Function and Interactions

Background: Hyperactive platelets contribute to different cardiovascular diseases. However, platelet function testing is preferentially applied for the diagnosis of platelet-related bleeding disorders.

Aims: This study aimed to 1) generate age- and sex-specific reference values for platelet (re)activity markers from population-based “cardiovascular healthy” individuals and 2) evaluate the discriminative potential of values outside reference ranges for cardiovascular disease.

Methods: A “cardiovascular healthy” subgroup (n=341; 51% female) was defined in the Gutenberg Health Study after exclusion of cardiovascular-related diseases and medications. This study was approved by the local Ethics Committee including signed participant informed consent. The 5th/95th percentiles defined platelet function reference values. Age-/sex-dependency and cardiovascular risk determinants of platelet function parameters (flow cytometry, light transmission aggregometry, PFA-200, calibrated automated thrombography) were assessed by multivariable linear regression. Age-/sex-adjusted logistic regression in the total sample (n=789) estimated the probability of having coronary artery disease (CAD), myocardial infarction (MI), stroke, atrial fibrillation (AF), chronic heart failure (CHF) and venous thromboembolism (VTE) for values outside the reference range.

Results: Men (median:2.60%,IQR:1.20/5.31) showed higher percentage of CD63+ platelets than women (1.90%,0.70/3.68), which both decreased with age. Spontaneous and collagen-induced platelet aggregability increased (β [log-transformed dependent variable, DV]=0.096,p=0.002; β=1.59,p=0.036) and collagen/ADP-induced closure time decreased (β [log-transformed DV]=-0.03,p=0.038) with age. Tissue factor-induced endogenous thrombin potential (ETP) decreased (β=-33.8,p=0.018) and lag time increased (β=0.327,p=0.0078) with age. Arterial hypertension, obesity and active smoking were age, sex and other risk factor-independent determinants of platelet aggregability, thrombin generation and ex vivo activation. Values outside the reference range for collagen-induced platelet aggregability and thrombin generation were related to increased prevalence of CAD, MI, AF, CHF and VTE. History of stroke and VTE were more prevalent with values exceeding the reference range for CD63+ platelets (OR:5.77;95%CI:1.42;23.41;p=0.014) and spontaneous aggregation (OR:2.75;95%CI:1.14;6.66;p=0.025), respectively.

Conclusion(s): Platelet function test values outside of population-based reference ranges may be useful markers of cardiovascular disease.

To cite this abstract in AMA style:

von Ungern-Sternberg S, Panova-Noeva M, ten Cate V, Dahlen B, Buch G, Rapp S, Prochaska J, Strauch K, Beutel M, Schuster A, Lackner K, Münzel T, Wild P, Jurk K. Population-based reference ranges of platelet function tests and their discriminative ability for cardiovascular disease [abstract]. https://abstracts.isth.org/abstract/population-based-reference-ranges-of-platelet-function-tests-and-their-discriminative-ability-for-cardiovascular-disease/. Accessed September 21, 2023.

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