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Reliability of hemostasis biomarkers is affected by time‐dependent intra‐patient variability
Author(s): ,
S. Bouvier
Affiliations:
Department of Haematology, University Hospital, Nîmes, France. Research Laboratory EA 2992, Montpellier University, Montpellier, France. Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France
Correspondence: Sylvie Bouvier, Department of Haematology, Nîmes University Hospital, Place du Professeur Robert Debré, Nîmes, 30029, France|Tel.: +33 466 683 211|E‐mail: sylvie.bouvier@chu-nimes.fr
,
S. Bastide
Affiliations:
Department of Biostatistics, Public Health and Innovation in Methodology, Nîmes University Hospital, Nîmes, France. Research Laboratory EA 2415, Montpellier University, Montpellier, France
,
S. Chouirfa
Affiliations:
Department of Haematology, University Hospital, Nîmes, France
,
É. Nouvellon
Affiliations:
Department of Haematology, University Hospital, Nîmes, France. Research Laboratory EA 2992, Montpellier University, Montpellier, France
,
É. Mercier
Affiliations:
Department of Haematology, University Hospital, Nîmes, France. Research Laboratory EA 2992, Montpellier University, Montpellier, France. Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France
,
L. Bigot
Affiliations:
Department of Haematology, University Hospital, Nîmes, France
,
G. Lavigne
Affiliations:
Department of Haematology, University Hospital, Nîmes, France. Research Laboratory EA 2992, Montpellier University, Montpellier, France
,
G. Cayla
Affiliations:
Department of Cardiology, University Hospital, Nîmes, France
,
A. Pérez‐Martin
Affiliations:
Research Laboratory EA 2992, Montpellier University, Montpellier, France. Department of Vascular Medicine, University Hospital, Nîmes, France
J.‐C. Gris
Affiliations:
Department of Haematology, University Hospital, Nîmes, France. Research Laboratory EA 2992, Montpellier University, Montpellier, France. Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France
ISTH Academy. Bouvier S. Aug 2, 2018; 227426
Dr. Sylvie Bouvier
Dr. Sylvie Bouvier

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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.
Keyword(s)
D‐dimers, fibrinogen, nucleosomes, plasma free DNA, reliability, venous thromboembolism
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