Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2749-6046
Coagulation and Fibrinolysis

Laboratory Monitoring of UFH in Different Settings (DEXHEP Study): Association between Anti-Xa Levels, Platelet Factor 4 (PF4) Plasma Levels and Dextran Sulfate

Authors

  • Philippe Savard

    1   Centre Hospitalier Universitaire de Dijon (CHU Dijon), Dijon, France
  • Emmanuel Curis

    2   UR 7537 BioSTM, Université Paris Cité & Hôpital Lariboisière, Paris, France
  • Isabelle Gouin-Thibault

    3   Centre Hospitalier Universitaire de Rennes (CHU Rennes), Rennes, France
  • Marie Toussaint-Hacquard

    4   Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nancy, France
  • Céline Delassasseigne

    5   Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Bordeaux, France
  • Anne Bauters

    6   Centre Hospitalier Régional Universitaire de Lille (CHU Lille), Lille, France
  • Claire Flaujac

    7   Centre Hospitalier de Versailles (CH Versailles), Versailles, France
  • Valérie Eschwège

    4   Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nancy, France
  • Christine Mouton

    5   Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Bordeaux, France
  • Thomas Lecompte

    3   Centre Hospitalier Universitaire de Rennes (CHU Rennes), Rennes, France
    4   Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nancy, France
    8   Faculté de Médecine, Université de Lorraine, Nancy, France
  • Emmanuel de Maistre

    1   Centre Hospitalier Universitaire de Dijon (CHU Dijon), Dijon, France
  • Dominique Lasne

    9   UMR-S-1176, Hôpital Necker—AP-HP, Paris, France
  • Virginie Siguret

    10   UMR-S-1144, Hôpital Lariboisière—AP-HP, Paris, France

Funding Information This work was supported by the Société Française de Thrombose et d'Hémostase (SFTH, French Society on Thrombosis and Haemostasis).


Graphical Abstract

Abstract

Background

Chromogenic anti-Xa assay is currently used in the management of patients on unfractionated heparin (UFH). It has been shown that inter-assay variability in anti-Xa levels can be explained in part by the presence or absence of dextran sulfate (DXS) in the reagents. DXS has the ability to dissociate UFH from neutralizing proteins, including platelet factor 4 (PF4).

Aims

Investigate whether PF4 plasma levels along with the presence/absence of DXS in anti-Xa reagents are associated with variations in UFH anti-Xa levels in different clinical situations.

Methods

In the prospective multicenter study DEXHEP-NCT04700670, critically ill patients on UFH therapy (four groups) were recruited. Blood was collected into citrate and CTAD tubes. Chromogenic anti-Xa levels were assessed using seven reagent/analyzer combinations including two without DXS. Plasma PF4 was measured by ELISA (Zymutest-PF4-Hyphen-Biomed).

Results

A total of 144 patients were analyzed: average PF4 levels in citrate plasma samples were consistently higher than in CTAD ones (206 vs. 46 ng/mL, p < 10−4), regardless of the patient group. Using a linear mixed-effect model, we found a significant effect of both DXS and PF4 on anti-Xa level, with a significant interaction term (p < 10−4). Considering the 0.3 to 0.7 IU/mL therapeutic range, agreement between anti-Xa values (Liquid-anti-Xa/DXS-free vs. Biophen-LRT/DXS) was observed in roughly two-thirds of the patients.

Conclusion

PF4 levels slightly affects anti-Xa levels, the use of CTAD tubes minimizing the effect. However, PF4 levels do not fully explain the differences of anti-Xa levels observed in the presence or absence of DXS, which has a greater effect. Anti-Xa assays require better standardization.



Publication History

Received: 16 August 2025

Accepted after revision: 22 October 2025

Accepted Manuscript online:
18 November 2025

Article published online:
02 December 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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