Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study

Ingrid M Bistervels; Hanke M G Wiegers; Fionnuala Ní Áinle; Suzanne M Bleker; Céline Chauleur; Jennifer Donnelly; Anne F Jacobsen; Marc A Rodger; Maria T DeSancho; Peter Verhamme; Anette T Hansen; Roman G Shmakov; Wessel Ganzevoort; Andrea Buchmüller; Saskia Middeldorp; Highlow Investigators

doi:10.1016/j.jtha.2022.11.004

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study

J Thromb Haemost. 2023 Jan;21(1):57-67. doi: 10.1016/j.jtha.2022.11.004. Epub 2022 Dec 22.

Authors

Ingrid M Bistervels¹, Hanke M G Wiegers², Fionnuala Ní Áinle³, Suzanne M Bleker², Céline Chauleur⁴, Jennifer Donnelly⁵, Anne F Jacobsen⁶, Marc A Rodger⁷, Maria T DeSancho⁸, Peter Verhamme⁹, Anette T Hansen¹⁰, Roman G Shmakov¹¹, Wessel Ganzevoort¹², Andrea Buchmüller¹³, Saskia Middeldorp¹⁴; Highlow Investigators

Affiliations

¹ Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: i.m.bistervels@amsterdamumc.nl.
² Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
³ Department of Hematology, Rotunda Hospital and Mater Misericordiae University Hospital, Dublin, Ireland; Irish Network for Venous Thromboembolism Research, Dublin, Ireland; School of Medicine University College Dublin, Dublin, Ireland.
⁴ INSERM, Clinical Investigator Center 1408 - F Crin, INNOVTE, Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Service Médecine Vasculaire et Thérapeutique, France; Department of Obstetrics & Gynaecology, Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France; INSERM, SAINBIOSE, U1059, Dysfonction Vasculaire et Hémostase, Université Jean-Monnet, Saint-Etienne, France.
⁵ Department of Obstetrics and Gynaecology, Rotunda Hospital and Mater Misericordiae University Hospital, Dublin, Ireland; Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.
⁶ Department of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Hospital, Oslo, Norway.
⁷ Department of Hematology, The Ottawa Hospital, Ottawa, Canada.
⁸ Department of Medicine, Division of Hematology-Oncology, New York Presbyterian Hospital, Weill Cornell Medicine, New York, New York, USA.
⁹ Department of Cardiovascular Sciences, Vascular Medicine and Haemostasis, KU Leuven, Leuven, Belgium.
¹⁰ Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
¹¹ Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, Moscow, Russia.
¹² Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹³ INSERM, Clinical Investigator Center 1408 - F Crin, INNOVTE, Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Service Médecine Vasculaire et Thérapeutique, France; Department of Vascular Medicine/Service Médecine Vasculaire et Thérapeutique, Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France.
¹⁴ Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Internal Medicine & Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

PMID: 36695396
DOI: 10.1016/j.jtha.2022.11.004

Abstract

Background: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose.

Objectives: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH.

Methods: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH.

Results: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%).

Conclusion: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.

Keywords: anesthesia and analgesia; heparin; labor; low-molecular-weight; obstetric; pregnancy; venous thromboembolism.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Analgesia*
Anticoagulants / therapeutic use
Female
Heparin, Low-Molecular-Weight / therapeutic use
Humans
Male
Pregnancy
Venous Thromboembolism* / drug therapy

Substances

Heparin, Low-Molecular-Weight
Anticoagulants

Associated data

ClinicalTrials.gov/NCT01828697