Marc Righini, MD; Helia Robert-Ebadi, MD; Antoine Elias, MD, PhD; Olivier Sanchez, MD, PhD; Emmanuelle Le Moigne, MD; Jeannot Schmidt, MD; Catherine Le Gall, MD; Jacques Cornuz, MD, PhD; Drahomir Aujesky, MD, MSc; Pierre-Marie Roy, MD, PhD; Céline Chauleur, MD, PhD; Olivier T. Rutschmann, MD; Pierre-Alexandre Poletti, MD; Grégoire Le Gal, MD, PhD; for the CT-PE-Pregnancy Group *
Note: All authors had access to all of the data in the study, read and approved the final manuscript, and were responsible for the decision to submit it for publication.
Acknowledgment: The authors thank the members of the adjudication committee for their important contribution (Françoise Boehlen, MD, Geneva University Hospital; Marc Carrier, MD, MSc, Ottawa Hospital Research Institute; and François Becker, MD, Geneva University Hospital) as well as all of the residents and physicians from the emergency departments and vascular medicine units of all participating centers. They also thank all study nurses, secretaries, and clinical research technicians for their invaluable help (in Angers, Béatrice Gable [clinical research technician] and Aurore Hamard [nurse]; in Brest, Pauline Stéphan [clinical research technician]; in Clermont-Ferrand, Christelle Camminada [clinical research technician]; in Paris, Amélie Marquette, Céline Haton, and Siwar Smii [clinical research technicians]; in Toulon, Danielle Giansily, Audrey Gruel, and Claudie Leclercq [nurses]; and in Geneva, Louise Riberdy [nurse], Nadège Antoine Koffi Malan [clinical research technician], and Floriane Le Petit Le Danvic [nurse]). The authors thank the staff of the Clinical Research Center at Geneva University Hospital, particularly Khaled Mostaguir (clinical research associate [no compensation]), who developed the electronic case report form for the study, as well as the coordinating center in Brest for French study sites (Isabelle Pichon [multicenter coordinator], Elise Poulhazan, Céline Dolou, Florence Morvan, Véronique Kouassi, and Floriane Masson). Finally, the authors thank the patients who made the study possible by agreeing to participate.
Grant Support: The study was supported by grants from the Swiss National Foundation for Scientific Research (FNS32003B-120760), the Groupe d'Etude de la Thrombose de Bretagne Occidentale, and the International Society on Thrombosis and Haemostasis Presidential Grant (2017). Dr. Le Gal holds an Early Researcher Award from the Province of Ontario; a “CP Has Heart” cardiovascular clinician scientist award from the Heart and Stroke Foundation of Ontario; and the Chair on Diagnosis of Venous Thromboembolism from the Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Disclosures: Dr. Sanchez reports grants from Bayer, MSD, Bristol-Myers Squibb, Daiichi Sankyo, and Actelion; personal fees from Bayer, MSD, Bristol-Myers Squibb, and Sanofi Aventis; and nonfinancial support from Bayer, MSD, Bristol-Myers Squibb, and Actelion outside the submitted work. Dr. Le Gal reports other support from Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, LEO Pharma, Daiichi Sankyo, Bayer, Sanofi, and bioMérieux outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1670.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Righini (e-mail, Marc.Righini@hcuge.ch). Data set: Not available; however, eligible researchers who want to propose their own analyses may contact Dr. Righini.
Corresponding Author: Marc Righini, MD, Division of Angiology and Hemostasis, Department of Medical Specialties, Geneva University Hospitals and Faculty of Medicine, 4, rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland; e-mail, Marc.Righini@hcuge.ch.
Current Author Addresses: Drs. Righini and Robert-Ebadi: Division of Angiology and Hemostasis, Department of Medical Specialties, Geneva University Hospitals and Faculty of Medicine, 4, rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland.
Dr. Elias: Vascular Medicine, Hôpital Sainte Musse, 54, rue Henri Sainte Claire, 83056 Toulon, France.
Dr. Sanchez: Service de Pneumologie et Soins Intensif, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
Dr. Le Moigne: EA3878, Département de Médecine Interne et de Pneumologie, Groupe d'Etude de la Thrombose de Bretagne Occidentale, Université de Brest, 2, avenue Foch, 29609 Brest, France.
Dr. Schmidt: Centre Hospitalier Universitaire, Pôle Urgences, CHU G. Montpied, 58 rue Montalembert, Clermont-Ferrand, France.
Dr. Le Gall: Emergency Department, Centre Hospitalier Général, 69 rue colonel Prud'hon, 95100 Argenteuil, France.
Dr. Cornuz: Department of Ambulatory Care and Community Medicine, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 44, 1011 Lausanne, Switzerland.
Dr. Aujesky: Klinik für Allgemeine Innere Medizin, Bern University Hospital, Inselspital, 3010 Bern, Switzerland.
Dr. Roy: Department of Emergency Medicine, University Hospital of Angers, 4 rue Larrey, 49933 Angers, France.
Dr. Chauleur: Service de Gyéncologie-Obstétrique, Saint-Etienne University Hospital, Avenue Albert Raimond, 42270 Saint-Etienne, France.
Dr. Rutschmann: Division of Emergency Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Dr. Poletti: Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Dr. Le Gal: Médecine interne 1, Brest University Hospital, CHU de la Cavale Blanche, 29609 Brest, France.
Author Contributions: Conception and design: M. Righini, H. Robert-Ebadi, G. Le Gal.
Analysis and interpretation of the data: M. Righini, H. Robert-Ebadi, A. Elias, J. Schmidt, P.M. Roy, O.T. Rutschmann, P.A. Poletti, G. Le Gal.
Drafting of the article: M. Righini, H. Robert-Ebadi, A. Elias, J. Schmidt, P.M. Roy, P.A. Poletti, G. Le Gal.
Critical revision of the article for important intellectual content: M. Righini, H. Robert-Ebadi, A. Elias, O. Sanchez, J. Cornuz, D. Aujesky, O.T. Rutschmann, P.A. Poletti.
Final approval of the article: M. Righini, H. Robert-Ebadi, A. Elias, O. Sanchez, E. Le Moigne, J. Schmidt, C. Le Gall, J. Cornuz, D. Aujesky, P.M. Roy, C. Chauleur, O.T. Rutschmann, P.A. Poletti, G. Le Gal.
Provision of study materials or patients: M. Righini, A. Elias, O. Sanchez, E. Le Moigne, D. Aujesky, P.M. Roy, G. Le Gal.
Statistical expertise: M. Righini, G. Le Gal.
Obtaining of funding: M. Righini, G. Le Gal.
Administrative, technical, or logistic support: M. Righini, O.T. Rutschmann, P.A. Poletti, G. Le Gal.
Collection and assembly of data: M. Righini, H. Robert-Ebadi, A. Elias, O. Sanchez, E. Le Moigne, J. Schmidt, C. Le Gall, D. Aujesky, P.M. Roy, C. Chauleur, O.T. Rutschmann, P.A. Poletti, G. Le Gal.
Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests.
To prospectively validate a diagnostic strategy in pregnant women with suspected PE.
Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454)
11 centers in France and Switzerland between August 2008 and July 2016.
Pregnant women with clinically suspected PE in emergency departments.
Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation–perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months.
The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up.
441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasound [n = 7], positive CTPA result [n = 19], and high-probability V/Q scan [n = 2]) and excluded in 367 (clinical probability and negative D-dimer result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up.
There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE.
A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women.
Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.
Righini M, Robert-Ebadi H, Elias A, Sanchez O, Le Moigne E, Schmidt J, et al. Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study. Ann Intern Med. [Epub ahead of print ]:. doi: 10.7326/M18-1670
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Published: Ann Intern Med. 2018.
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