Frontiers in Cardiovascular Medicine (Feb 2025)

Age- and sex-dependency of thrombin generation parameters in the general Italian population: the Moli-sani study

  • Simona Costanzo,
  • Bas de Laat,
  • Bas de Laat,
  • Augusto Di Castelnuovo,
  • Lisa van der Vorm,
  • Amalia De Curtis,
  • Chiara Cerletti,
  • Marisa Ninivaggi,
  • Maria Benedetta Donati,
  • Licia Iacoviello,
  • Licia Iacoviello,
  • Romy de Laat-Kremers,
  • the Moli-sani investigators,
  • Licia Iacoviello,
  • Giovanni de Gaetano,
  • Maria Benedetta Donati,
  • Chiara Cerletti,
  • Marialaura Bonaccio,
  • Americo Bonanni,
  • Simona Costanzo,
  • Amalia De Curtis,
  • Augusto Di Castelnuovo,
  • Alessandro Gialluisi,
  • Francesco Gianfagna,
  • Mariarosaria Persichillo,
  • Teresa Di Prospero,
  • Jos Vermylen,
  • Renzo Pegoraro,
  • Antonio Spagnolo,
  • Deodato Assanelli,
  • Livia Rago,
  • Simona Costanzo,
  • Marco Olivieri,
  • Sabatino Orlandi,
  • Teresa Panzera,
  • Augusto Di Castelnuovo,
  • Marialaura Bonaccio,
  • Simona Costanzo,
  • Simona Esposito,
  • Alessandro Gialluisi,
  • Anwal Ghulam,
  • Francesco Gianfagna,
  • Antonietta Pepe,
  • Emilia Ruggiero,
  • Sukshma Sharma,
  • Amalia De Curtis,
  • Concetta Civitillo,
  • Alisia Cretella,
  • Sara Magnacca,
  • Fabrizia Noro,
  • Mariarosaria Persichillo,
  • Francesca Bracone,
  • Fiorella De Rita,
  • Giuseppe Di Costanzo,
  • Sabrina Franciosa,
  • Martina Morelli,
  • Americo Bonanni,
  • Ospedale A. Cardarelli-Campobasso,
  • Ospedale F. Veneziale-Isernia,
  • Ospedale San Timoteo-Termoli,
  • Ospedale Ss. Rosario-Venafro,
  • Ospedale Vietri-Larino,
  • Ospedale San Francesco Caracciolo-Agnone,
  • Casa di Cura Villa Maria-Campobasso

DOI
https://doi.org/10.3389/fcvm.2025.1528871
Journal volume & issue
Vol. 12

Abstract

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BackgroundRecent developments have made the thrombin generation (TG) test accessible to the clinical laboratory. Therefore, the clinical interpretation of TG parameters has become of increasing interest, and reference values are required. Age and sex have been shown to affect TG parameters, but no consensus has been reached on the subject. We investigated the effect of age and sex on TG parameters to determine the need for age and sex specific reference values for TG.MethodsTG was measured in 22,014 individuals of the Moli-sani study, a cross-sectional cohort of the general adult Italian population. TG was measured using Calibrated Automated Thrombinography in platelet poor plasma (PPP) using PPP reagent Low and PPP reagent, in the presence and absence of thrombomodulin (TM).ResultsIndividuals were grouped into 6 age categories: 35–44 years of age (n = 5,073), 45–54 (n = 6,448), 55–64 (n = 5,516), 65–74 (n = 3,539), 75–84 (n = 1,261), and 85 years of age and older (n = 106). Men and women were distributed evenly in the age categories. Smoking was more common at younger age, whereas cardiovascular diseases, hypertension, hypercholesterolemia, and diabetes were more common at older age (p < 0.001). Lag time and velocity index increased with age, whereas the endogenous thrombin potential (ETP) and time-to-peak decreased. The inhibitory effect of TM was reduced at higher age (p < 0.001). The TG lag time was shorter in women than men at younger age (6%–7% lower in women), and the ETP was lower in women. The activated protein C (APC) pathway was desensitized in women and older individuals.ConclusionThe TG profile becomes more “procoagulant” at older age, especially in women. The sensitivity of the APC pathway to TM is reduced with increasing age in men and women. Therefore, age and sex appropriate reference values for TG parameters would be of interest for the ongoing clinical implementation of the TG assay.

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