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Sequential use of the left rule, D-dimer measurement and complete ultrasonography to rule out deep vein thrombosis during pregancy: a prospective management study

English title Sequential use of the left rule, D-dimer measurement and complete ultrasonography to rule out deep vein thrombosis during pregancy: a prospective management study
Applicant Righini Marc
Number 146287
Funding scheme Project funding (Div. I-III)
Research institution Hôpitaux Universitaires de Genève Service d'Angiologie et d'Hémostase
Institution of higher education University of Geneva - GE
Main discipline Internal Medicine
Start/End 01.02.2014 - 31.01.2017
Approved amount 174'237.00
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All Disciplines (2)

Discipline
Internal Medicine
Clinical Cardiovascular Research

Keywords (5)

Deep vein thrombosis; Pregnancy; Diagnosis; D-dimer; Ultrasonography

Lay Summary (French)

Lead
Le diagnostic de thrombose veineuse profonde chez la femme enceinte demeure difficile et peu d'études sont disponibles. En particulier, les tests habituellement utilisés en cas de suspicion de thrombose en dehors de la grossesse n'ont que peu été évalués. L'étude proposée réunit ces examens peu invasifs (évaluation de la probabilité clinique, dosage sanguin des D-dimères et échographie) dans un seul algorithme qui sera évalué chez des femmes enceinte avec une suspicion clinique de thrombose.
Lay summary

Chez la femme enceinte suspecte de thrombose veineuse profonde (TVP) des membres inférieurs, un diagnostic de certitude, négatif ou positif, s’impose.

En dehors de la grossesse, la stratégie diagnostique de la thrombose veineuse profonde se base sur l’évaluation de la probabilité clinique, les D-dimères, et l’échographie de compression des membres inférieurs. Ces stratégies ont largement été validées dans des études prospectives.

Les données disponibles chez la femme enceinte sont bien plus limitées. Ainsi, l’évaluation de la probabilité clinique n’a été évaluée que dans des petites études et c’est seulement récemment qu’un score de probabilité clinique a été proposé, puis validé de manière externe. Ce score sépare les patientes en deux catégories, une dans laquelle la présence d’une thrombose est peu vraisemblable et une dans laquelle la présence d’une thrombose est vraisemblable. Ce score, dénommé « LEFt » (Left leg, Edema, First trimester presentation) n’a toutefois pas été validé de manière prospective.

En ce qui concerne l’utilisation des D-dimères pendant la grossesse, les données disponibles suggèrent que le seuil habituel de 500 ng/ml peut raisonnablement exclure la thrombose veineuse profonde chez la femme enceinte. Il n’y a ce jour toutefois pas de validation prospective solide. Finalement, l’échographie des membres inférieurs a bénéficié d’une validation prospective dans deux petites études avec un collectif total de patientes inférieur à 400 sujets.

Dans ce contexte, nous souhaitons mettre en place une étude prospective multicentrique validant l’utilisation séquentielle du score LEFt, des D-dimères et de l’échographie complète chez la femme enceinte avec une suspicion de thrombose veineuse profonde.

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Direct link to Lay Summary Last update: 02.09.2013

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
Ottawa research group on venous thromboembolic disease Canada (North America)
- Publication
French reseach group on venous thromboembolic disease France (Europe)
- Publication

Associated projects

Number Title Start Funding scheme
159510 Age-adjusted D-Dimer cutoff levels to rule out deep vein thrombosis: a prospective outcome study. The adjust-DVT study 01.10.2015 Project funding (Div. I-III)
130863 Age-adjusted D-dimer cut-off levels to rule out pulmonary embolism: a prospective outcome study. 01.04.2011 Project funding (Div. I-III)

Abstract

In pregnant women with suspected DVT, a sure diagnosis is mandatory. Indeed, false positive tests lead to inappropriate anticoagulant treatment, which increases the risk of bleeding. Conversely, false negative tests might lead to a life-threatening thromboembolic event. Thus, accuracy of diagnostic methods used in pregnant women is crucial [1]. In non-pregnant patients, sequential diagnostic strategies based on 1) the assessment of clinical probability, 2) D-dimer measurement and 3) compression ultrasonography (CUS) have been widely validated [2, 3].Clinical probability assessment by clinical prediction rules (CPRs) is a crucial step in the management of suspected DVT. However, the most commonly used CPR for DVT, the Wells’ score, has never been validated in pregnant women [3]. Recently, the ‘LEFt’ clinical prediction rule was derived and internally validated by Chan et al. among 194 pregnant women investigated for suspected DVT[4]. This rule combines three variables: symptoms in the left leg (“L”), calf circumference difference equal or greater than 2 centimeters (“E” for edema) and first trimester presentation (“Ft”) [4]. We performed an external validation of this rule on a recently published prospective cohort of pregnant patients with suspected DVT (submitted to JTH). This external validation showed that a negative “LEFt” rule accurately identified pregnant women in whom the proportion of confirmed DVT appears to be very low. A prospective validation of this rule is now warranted, and we plan to use it in our prospective study.The second step used in the diagnostic strategy including non-pregnant patients is D-dimer measurement. The test has been widely validated in non-pregnant patients and, in association with a non-high clinical probability, it allows to safely rule out DVT [5].As D-dimer level raise steadily during pregnancy, the specificity of the test decreases and it is less useful in pregnant women. A recent study suggested that the currently available sensitive D-dimer assays that are used for the exclusion in symptomatic non-pregnant women have the potential to exclude DVT in symptomatic pregnant women with the application of higher cut-points [6]. Even if this data arises from a small study, it clearly suggests that the usual cut-off set a 500 ng/ml would safely rule out DVT in pregnant women [6]. As the usual cut-off has never been prospectively validated in pregnant women with suspected DVT, we would like, as a first step, to use it in our study.In pregnant patients, limited data is available on the use of complete compression ultrasonography to rule out DVT. In a recent prospective management study, we included 226 pregnant and post-partum women with suspected lower limb DVT. We observed a 1.1% (95% CI:0.3-4.0) three-month thromboembolic event rate in those left untreated on the basis of a negative single complete CUS [7]. This result is in line with what was reported after a normal phlebography, the gold standard test [8].Even if complete CUS is safe to rule out DVT in pregnant women, current diagnostic strategies for suspected DVT in non-pregnant patients rely on the use of clinical probability and D-Dimer prior to leg veins imaging [5]. However, no management outcome study on the safety and usefulness of D-Dimer to rule out DVT in pregnant women is available to date. Another limitation of the strategies based on a single unique complete CUS, is that every woman has to undergo complete CUS. However, this test is not always available. Therefore, a strategy in which the association of clinical probability assessment and D-dimer measurement would allow to safely rule out DVT in a significant proportion of patients without performing a complete CUS, would be of great help in everyday clinical practice and would probably be cost-effective.Therefore, we plan a prospective study to assess the safety of a sequential diagnostic strategy based on the assessment of clinical probability with the LEFt rule, D-dimer measurement and complete CUS in pregnant women with suspected DVT.
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