Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability

Sylvie Bouvier (1, 2, 3) , S. Bastide (1, 4) , S. Chouirfa (1) , É Nouvellon (1, 2) , É Mercier (1, 2, 3) , L. Bigot (1) , G. Lavigne (1, 2) , G. Cayla (1, 3) , Antonia Perez-Martin (1, 2) , Jean-Christophe Gris (1, 2, 3)

1 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
2 EA 2992 - Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires
3 UM - Université de Montpellier
4 AIDMP - Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415

Essentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6~months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted.

Mots clés: D-dimers; fibrinogen; nucleosomes; plasma free DNA; reliability; venous thromboembolism

Domaines: Sciences du Vivant [q-bio]

Sylvie Bouvier, S. Bastide, S. Chouirfa, É Nouvellon, É Mercier, et al.. Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability. Journal of Thrombosis and Haemostasis, 2018, ⟨10.1111/jth.14198⟩. ⟨hal-02361111⟩