Benefit of Risk Score-Guided Prophylaxis in Pregnant Women at Risk of Thrombotic Events: A Controlled Before-and-After Implementation StudyFunding This study was sponsored by the University Hospital of Saint Etienne and supported by grants from the French Ministry of Health (Hospital Clinical Research Program PHRC IR 0508080) in 2005 and 2010, and a grant from Bourse LIVE.
23 November 2017
05 July 2018
13 August 2018 (eFirst)
Background Management of pregnant women at risk of venous thromboembolism (VTE) and placental vascular complications (PVCs) remains complex. Guidelines do not definitively specify optimal strategies.
Objective Our objective was to evaluate the impact of employing risk score-driven prophylaxis strategies on VTE and PVC rates in at-risk pregnant women.
Materials and Methods This study, conducted in 21 French maternity units, compared VTE and PVC rates before and after implementation of a risk scoring system to determine prophylactic strategies.
Results A total of 2,085 pregnant women at risk of VTE or PVC were enrolled. Vascular events occurred in 190 (19.2%) patients before and 140 (13.0%) after implementation of risk score-driven prophylaxis (relative risk [RR] = 0.68 [0.55; 0.83]). The incidence of deep vein thrombosis during pregnancy was reduced (RR = 0.30 [0.14; 0.67]). PVC comprised mainly pre-eclampsia, occurring in 79 patients before and 42 patients after risk score implementation (RR = 0.52 [0.36; 0.75]). Post-partum haemorrhage occurred in 32 patients (3.2%) before and 48 patients (4.5%) after risk score implementation (RR = 1.38 [0.89; 2.13], p = 0.15).
Conclusion Use of a simple risk scoring system, developed by experts in VTE and PVC research to guide prophylaxis, reduced the risk of thrombotic events during pregnancy without any significant increase in bleeding risk.
C. Chauleur: Literature search, study design, data collection, data analysis, data interpretation and writing of the manuscript. J. C. Gris: Data interpretation and writing of the manuscript. S. Laporte, C. Chapelle and L. Bertoletti: Data analysis, data interpretation and writing of the manuscript. V. Equy, P. Gaucheran, E. Bazan, O. Dupuis and D. Gallot: Contributed equally to data collection. P. Mismetti: Study design.
STRATHEGE Investigators and STRATHEGE Group: Contributed equally to study design and data collection.
Members of the STRATHEGE Group
Prof. D. Benhamou: Paris - Kremlin-Bicêtre, Dr. C. Biron-Andreani: Montpellier, Dr. J. Y. Borg: Rouen, Prof. C. Chauleur: Saint-Etienne, Dr. J. Conard: Paris, Dr. E. Demaistre: Dijon, Prof. L. Drouet: Lariboisière, Paris, Dr. P. Edelman: Paris, Prof. J. Emmerich: HEGP, Paris, Prof. P. Gaucherand: Lyon, Prof. J. C. Gris: Nîmes, Prof. Y. Gruel: Tours, Prof. B. Jude: Lille, Dr. J. L. Lorenzini: Dijon, Prof. P. Mismetti: Saint-Etienne, Dr. E. Pasquier: Brest, Prof. G. Pernod: Grenoble, Dr. A. Robert: Saint-Antoine, Paris, Dr. B. Tardy: Saint-Etienne, Dr. N. Trillot: Lille.
Members of the STRATHEGE Investigators
Dr. C. Chauleur, Dr. V. Equy, Dr. P. Gaucherand, Dr. E. Bazan, Dr. O. Dupuis, Dr. D. Gallot, Dr A. Favard, Dr. C. Huissoud, Dr. A. Cornu, Dr. J.F. Nord, Dr. C. Houlle, Dr. F. Ruesch, Dr. E. Magne, Dr. R. Ghawi, Dr. P. Mares, Dr. F. Champion, Dr. A.M. Forest, Dr. P. Boulot, Dr. F. Bousquet, Dr. L. Vulliez, Dr. G. Le Maout.
This protocol was approved by the ethics committee of the University Hospital of Saint Etienne on October 19th, 2006; and by the National Commission on Computerization and Freedom (Commission Nationale de l'Informatique et des Libertés [CNIL]): 908179; CTTIRS: 08.120. The study was registered with Clinicaltrials.gov (registry no. NCT0074521).
- 1 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e691S-e736S
- 2 Samama CM, Albaladejo P, Benhamou D. , et al; Committee for Good Practice Standards of the French Society for Anaesthesiology and Intensive Care (SFAR). Venous thromboembolism prevention in surgery and obstetrics: clinical practice guidelines. Eur J Anaesthesiol 2006; 23 (02) 95-116
- 3 Thromboembolic Disease in Pregnancy and the Puerperium. Acute Management. Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37b.pdf . Accessed March 5, 2016
- 4 Duhl AJ, Paidas MJ, Ural SH. , et al; Pregnancy and Thrombosis Working Group. Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 2007; 197 (05) 457.e1-457.e21
- 5 Bates SM, Greer IA, Pabinger I. , et al. American College of Chest Physicians. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed.). Chest 2008; 133: 844S-886S
- 6 Chauleur C, Gris JC, Laporte S. , et al; STRATHEGE Group. Use of the Delphi method to facilitate antithrombotics prescription during pregnancy. Thromb Res 2010; 126 (02) 88-92
- 7 Dargaud Y, Rugeri L, Vergnes MC. , et al. A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study. Br J Haematol 2009; 145 (06) 825-835
- 8 Lindqvist PG, Kublikas M, Dahlbäck B. Individual risk assessment of thrombosis in pregnancy. Acta Obstet Gynecol Scand 2002; 81 (05) 412-416
- 9 Bauersachs RM, Dudenhausen J, Faridi A. , et al; EThIG Investigators. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost 2007; 98 (06) 1237-1245
- 10 Weiss N, Bernstein PS. Risk factor scoring for predicting venous thromboembolism in obstetric patients. Am J Obstet Gynecol 2000; 182 (05) 1073-1075
- 11 Sarig G, Vidergor G, Brenner B. Assessment and management of high-risk pregnancies in women with thrombophilia. Blood Rev 2009; 23 (04) 143-147
- 12 Chauleur C, Quenet S, Varlet MN. , et al. Feasibility of an easy-to-use risk score in the prevention of venous thromboembolism and placental vascular complications in pregnant women: a prospective cohort of 2736 women. Thromb Res 2008; 122 (04) 478-484
- 13 Rodger MA, Carrier M, Le Gal G. , et al; Low-Molecular-Weight Heparin for Placenta-Mediated Pregnancy Complications Study Group. Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. Blood 2014; 123 (06) 822-828
- 14 Simcox LE, Ormesher L, Tower C, Greer IA. Thrombophilia and pregnancy complications. Int J Mol Sci 2015; 16 (12) 28418-28428
- 15 Areia AL, Fonseca E, Areia M, Moura P. Low-molecular-weight heparin plus aspirin versus aspirin alone in pregnant women with hereditary thrombophilia to improve live birth rate: meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2016; 293 (01) 81-86
- 16 Gris JC, Chauleur C, Faillie JL. , et al. Enoxaparin for the secondary prevention of placental vascular complications in women with abruptio placentae. The pilot randomised controlled NOH-AP trial. Thromb Haemost 2010; 104 (04) 771-779
- 17 de Jong PG, Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev 2014; 7 (07) CD004734
- 18 Gris JC, Mercier E, Quéré I. , et al. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103 (10) 3695-3699
- 19 Rodger MA, Hague WM, Kingdom J. , et al; TIPPS Investigators. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 2014; 384 (9955): 1673-1683
- 20 de Jong PG, Quenby S, Bloemenkamp KW. , et al. ALIFE2 study: low-molecular-weight heparin for women with recurrent miscarriage and inherited thrombophilia--study protocol for a randomized controlled trial. Trials 2015; 16: 208
- 21 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
- 22 Dargaud Y, Rugeri L, Négrier C, Trzeciak MC, Ninet J. Feasibility of an easy-to-use risk score in the prevention of venous thromboembolism and placental vascular complications in pregnant women. A rebuttal. Thromb Res 2008; 122 (05) 715-716
- 23 Bateman BT, Berman MF, Riley LE, Leffert LR. The epidemiology of postpartum hemorrhage in a large, nationwide sample of deliveries. Anesth Analg 2010; 110 (05) 1368-1373
- 24 Freedman RA, Bauer KA, Neuberg DS, Zwicker JI. Timing of postpartum enoxaparin administration and severe postpartum hemorrhage. Blood Coagul Fibrinolysis 2008; 19 (01) 55-59
- 25 James A. ; Committee on Practice Bulletins—Obstetrics. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol 2011; 118 (03) 718-729