key: cord-0047308-srhlu2xe
authors: Robert-Ebadi, H.; Righini, M.
title: D-dimer: Well beyond diagnosis!
date: 2020-07-09
journal: J Med Vasc
DOI: 10.1016/j.jdmv.2020.06.006
sha: f25f9cb6392bde40242bc3cef5a9eac0957d39d6
doc_id: 47308
cord_uid: srhlu2xe

nan

Reçu le 3 juin 2020 ; accepté le 3 juin 2020

Plasma D-dimer are measurable degradation products of cross-linked fibrin, whose levels increase in presence of a blood clot but also in various other situations associated with activated coagulation. Over the last 30 years, D-dimer have revealed their main strength as a diagnostic tool in venous thromboembolic diseases (VTE). Their central clinical usefulness indeed resides in their role as an exclusion test in patients with suspected VTE [1, 2] . Multiple large scale prospective management outcome trials have confirmed the safety of excluding pulmonary embolism (PE) and deep vein thrombosis (DVT) by a negative D-dimer test associated with a non-high pretest clinical probability [3] . Some more restricted evidence also suggests that D-dimer could allow ruling out aortic dissection in association with a low AAD-RS score [4] . Finally, D-dimer are used as a diagnostic tool in the setting of disseminated intravascular coagulation (DIC), and have been integrated in the latest ISTH overt-DIC diagnostic criteria [5] .

D-dimer have also been studied as a prediction tool in different settings such as prediction of VTE occurrence in acutely ill hospitalized medical patients to guide thromboprophylaxis prescription, or prediction of VTE recurrence after a first episode of unprovoked VTE to tailor duration of anticoagulant treatment. In acutely ill medical inpatients, a post-hoc analysis of the MAGELLAN trial (n = 7581) showed that a D-dimer level > 2 times the upper limit of normal range * Corresponding author.

Adresse e-mail : helia.robert-ebadi@hcuge.ch (H. Robert-Ebadi).

was an independent predictor of VTE events (OR compared to patients with D-dimer ≤ 2 times upper limit of normal range 2.29; 95% CI 1.75-2.98) [6] . For VTE recurrence prediction after a few months of anticoagulant treatment for a first idiopathic VTE, D-dimer levels -on anticoagulation or after anticoagulation cessation -have been extensively explored and included in all predictive models such as the Vienna Prediction Model, the HERDOO2 score, the DASH tool and the DAMOVES score [1].

Finally, the role of D-dimer as a prognostic tool has also been assessed, mainly in the setting of acute VTE. In a retrospective study published in 2006, Aujesky et al. showed that among patients with confirmed PE (n = 366), those who died had higher median D-dimer levels than patients who survived (4578 versus 2946 g/L; p= 0.005). Allcause mortality increased with increasing D-dimer levels, rising from 1.1% in the first quartile (<1500 g/L) to 9.1% in the fourth quartile (>5500 g/L) ( p= 0.049) [7] . These findings were recently confirmed in the COMMAND-VTE registry (n = 2852): D-dimer levels were again an independent predictor of all-cause mortality in patients with acute VTE. Indeed, mortality at 30 days was of 1.2% in the first quartile (<4900 g/L), 2.2% in the second quartile (5000-9900 g/L), 3.4% in the third quartile (10,000-19,900 g/L) and 8.4% in the fourth quartile (DD ≥ 20,000 g/L) [8] .

In mortality in the presented cohorts of patients with COVID-19. Of note, the increase in D-dimer levels did not seem to be the result of overt-DIC in these patients.

A high risk of VTE has been reported over the last few weeks in patients with severe COVID-19 (around 20-40% depending on the local systematic screening strategy) [9, 10] , which prompted physicians to empirically increase prophylactic anticoagulant dosing. Whether an intensified anticoagulant treatment -partly tailored to D-dimer levels -will impact mortality in these patients is currently under investigation in at least four randomised trials (COVID-HEP NCT04345848; IMPROVE NCT04367831; COVI-DOSE NCT04373707; RAPID COVID COAG NCT04362085).

Altogether, the recent data including those presented by Frère et al. in this issue highlight once again the great interest of D-dimer as a biomarker in clinical practice, not only as a diagnostic tool but also as a prognostic tool [11] .

The authors declare that they have no competing interest.

This manuscript represents original work, and it is not under consideration for publication elsewhere. It has never been neither submitted nor published in another scientific journal. All authors meet criteria for authorship and none of the authors have any conflict of interest. All read and approved the final manuscript, and held responsibility for the decision to submit it for publication. 

American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism

Diagnosis of acute pulmonary embolism

Diagnostic accuracy of the aortic dissection detection Risk Score Plus D-Dimer for acute aortic syndromes: the ADvISED prospective multicenter study

A re-evaluation of the D-dimer cut-off value for making a diagnosis according to the ISTH overt-DIC diagnostic criteria: communication from the SSC of the ISTH

D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial

Prognostic value of D-dimer in patients with pulmonary embolism

D-dimer levels at diagnosis and long-term clinical outcomes in venous thromboembolism: from the COMMAND VTE Registry

Venous thromboembolism in critically Ill patients with COVID-19: results of a screening study for deep vein thrombosis

Venous thromboembolism in COVID-19: systematic Review of reported risks and current guidelines

Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis