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Thromb Haemost 2023; 123(12): 1105-1115
DOI: 10.1055/s-0043-1770096
Coagulation and Fibrinolysis

Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin

Dominique Lasne 
1   AP-HP, Laboratoire d'hématologie générale, Hôpital Necker, INSERM, Univ. Paris-Saclay, Le Kremlin-Bicêtre, France
,
Marie Toussaint-Hacquard
2   Hématologie Biologique, CHRU Nancy, Nancy, France
,
Céline Delassasseigne
3   Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU Bordeaux, France
,
Anne Bauters
4   CHU Lille, Institut d'Hématologie—Transfusion, Lille, France
,
Claire Flaujac
5   Laboratoire de Biologie Médicale (Secteur Hémostase), Centre Hospitalier de Versailles, André Mignot, Le Chesnay, France
,
Philippe Savard
6   Hématologie Biologique, CHU Dijon Bourgogne, Dijon, France
,
Christine Mouton
3   Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU Bordeaux, France
,
Emmanuel De Maistre
6   Hématologie Biologique, CHU Dijon Bourgogne, Dijon, France
,
Alain Stepanian
7   AP-HP, Service d'Hématologie Biologique, Hôpital Lariboisière, Paris Cité University, Paris, France
,
Valérie Eschwège
2   Hématologie Biologique, CHRU Nancy, Nancy, France
,
Maxime Delrue
7   AP-HP, Service d'Hématologie Biologique, Hôpital Lariboisière, Paris Cité University, Paris, France
,
Jean-Louis Georges
8   Service de réanimation medico-chirurgicale, Centre Hospitalier de Versailles, André Mignot, Le Chesnay, France
,
Antoine Gros
8   Service de réanimation medico-chirurgicale, Centre Hospitalier de Versailles, André Mignot, Le Chesnay, France
,
Alexandre Mansour
9   Department of Anesthesia and Critical Care, Pontchaillou, University Hospital of Rennes; Univ Rennes, CHU Rennes, Inserm, IRSET, Rennes, France
,
Guillaume Leroy
10   CHU Lille, Pôle d'anesthesie-Réanimation, Lille, France
,
Romain Jouffroy
11   AP-HP, Service de réanimation adulte, Hôpital Necker, Paris, France
,
Matthieu Mattei
12   Unité d'Anesthésie et Réanimation Cardiaque & Réanimation Médicale Brabois, CHRU Nancy, Nancy, France
,
Antoine Beurton
13   Department of Cardiovascular Anaesthesia and Critical care, Surgical Medical Center Magellan, Haut-Lévêque Hospital, Pessac, France
,
Adeline Pontis
14   Hématologie Biologique, Hôpital Pontchaillou, University Hospital of Rennes, Univ. Rennes, CHU Rennes, Inserm, IRSET, Rennes, France
,
Marie Neuwirth
7   AP-HP, Service d'Hématologie Biologique, Hôpital Lariboisière, Paris Cité University, Paris, France
,
Fabienne Nedelec-Gac
14   Hématologie Biologique, Hôpital Pontchaillou, University Hospital of Rennes, Univ. Rennes, CHU Rennes, Inserm, IRSET, Rennes, France
,
Thomas Lecompte
15   Department of Pharmacy, Faculté de médecine, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université de Lorraine & Université de Namur, Namur, Belgium
16   Hématologie Biologique, Hôpital Pontchaillou University Hospital of Rennes, Rennes, France
,
Emmanuel Curis
17   UR 7537 BioSTM, faculté de pharmacie de Paris, université Paris Cité, Paris, France
18   Service d'Hématologie Biologique, Hôpital Lariboisière, AP-HP, Paris, France
,
Virginie Siguret   *
7   AP-HP, Service d'Hématologie Biologique, Hôpital Lariboisière, Paris Cité University, Paris, France
,
Isabelle Gouin-Thibault   *
14   Hématologie Biologique, Hôpital Pontchaillou, University Hospital of Rennes, Univ. Rennes, CHU Rennes, Inserm, IRSET, Rennes, France
› Author Affiliations Funding The reagents were purchased through a donation from the Bioformation Association (European Institute for Training).
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Abstract

Background The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels.

Objectives To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670).

Methods We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization (n = 39); G2, cardiothoracic intensive care unit (ICU) after CPB (n = 35); G3, medical ICU (n = 53); G4, other medical inpatients (n = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model.

Results We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs. 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran–patient group interaction (p < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups (p = 0.0302).

Conclusion The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated.

Keywords

heparin - neutralizing proteins - monitoring - anti-Xa inhibitors

* Prof. Siguret and Dr. Gouin-Thibault contributed equally to this article.


Supplementary Material



Publication History

Received: 23 January 2023

Accepted: 15 May 2023

Article published online:
15 June 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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