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Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2749-6046
Original Article

Laboratory monitoring of UFH in different settings (DEXHEP study): association between anti-Xa levels, PF4 plasma levels and dextran sulfate

Autoren

  • Philippe SAVARD

    1   Hématologie Biologique, CHU Dijon Bourgogne, Dijon, France (Ringgold ID: RIN36659)

  • Emmanuel Curis

    2   UR 7537 BioSTM (Biostatistics), Université Paris Cité, Paris, France (Ringgold ID: RIN555089)
    3   AP-HP Hématologie Biologique, Hôpital Lariboisière, Paris, France (Ringgold ID: RIN378772)

  • Isabelle Gouin-Thibault

    4   Hématologie Biologique, Hopital Pontchaillou, Rennes, France (Ringgold ID: RIN55065)

  • Marie Toussaint-Hacquard

    5   Hématologie biologique, CHRU de Nancy, Nancy, France (Ringgold ID: RIN26920)

  • Céline Delassasseigne

    6   Hématologie biologique, CHU de Bordeaux, Talence, France (Ringgold ID: RIN36836)

  • Anne Bauters

    7   Institut d’Hématologie-Transfusion, Centre de biologie Pathologie, CHU de Lille, Lille, France (Ringgold ID: RIN26902)

  • Claire Flaujac

    8   Laboratoire de Biologie Médicale, Centre Hospitalier de Versailles, Le Chesnay, France (Ringgold ID: RIN26938)

  • Christine Mouton

    9   Hématologie biologique, Université de Bordeaux, Talence, France (Ringgold ID: RIN27086)

  • Thomas Lecompte

    10   Faculté de Médecine, Université de Lorraine - Site de Nancy, Nancy, France (Ringgold ID: RIN137665)
    11   Hématologie biologique, CHU de Rennes, Rennes, France (Ringgold ID: RIN36684)

  • emmanuel demaistre

    1   Hématologie Biologique, CHU Dijon Bourgogne, Dijon, France (Ringgold ID: RIN36659)

  • Dominique Lasne 

    12   Laboratoire d'hématologie général, Hopital universitaire Necker-Enfants malades, Paris, France (Ringgold ID: RIN246596)
    13   UMR_S 1176, INSERM, Le Kremlin-Bicêtre, France (Ringgold ID: RIN27102)

  • Virginie Siguret 

    3   AP-HP Hématologie Biologique, Hôpital Lariboisière, Paris, France (Ringgold ID: RIN378772)
    14   INSERM UMR_S1144, Université Paris Cité, Paris, France (Ringgold ID: RIN555089)

Gefördert durch: Société Française de Thrombose et d'Hémostase

Clinical Trial:

Registration number (trial ID): NCT04700670, Trial registry: ClinicalTrials.gov (http://www.clinicaltrials.gov/), Type of Study: prospective observational multicentre study


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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 (4 groups) were recruited. Blood was collected into citrate and CTAD tubes. Chromogenic anti-Xa levels were assessed using 7 reagent/analyzer combinations including 2 without DXS. Plasma PF4 was measured by ELISA (ZymutestTM-PF4-Hyphen-Biomed). Results: 144 patients were analysed: average PF4 levels in citrate plasma samples were consistently higher than in CTAD ones (206 vs 46 ng/mL, p<10-4), regardless 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 0.3-0.7 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 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.



Publikationsverlauf

Eingereicht: 16. August 2025

Angenommen nach Revision: 22. Oktober 2025

Accepted Manuscript online:
18. November 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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