Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications
Authors: Loffredo Lorenzo , Vidili Gianpaolo , Sciacqua Angela , Cogliati Chiara , Di Giulio Rosella , Bernardini Sciaila , Ciacci Paolo , Pietrangelo Antonello , Orlando Federica , Paraninfi Aurora , Boddi Maria , Di Minno Giovanni , Falsetti Lorenzo , Lodigiani Corrado , Santoliquido Angelo , Ettorre Evaristo , Pignatelli Pasquale , Arezzo Maria Felice , Gutu Evghenii , Harenberg Job , Violi Francesco ,   AURELIO Study Group, Casciaro Marco Antonio , Morelli Sergio , Accapezzato Daniele , Rossi Elisabetta , Palumbo Ilaria Maria , Pannunzio Arianna , Fallarino Alessia , Maggio Enrico , Bocchini Valeria Proietti , Gioia Chiara , Izzo Raffaella , Luongo Raffaella , Cosenza Mattia , Bisciglia Maria Francesca , Battaglia Simona , Pirillo Lohengrin Stefania , Capozza Alessandro , Summa Maria Luna , Armentaro Giuseppe , Volpentesta Mara , Rullo Raissa , Baldinia Lorenzo , Arienti Vincenzo , Meloni Pier Luigi , Sauchella Assunta , Melis Sara , Berria Maria , Solinas Beatrice , Vilardi Luca , Sarobba Paola , Pisanu Manuela , Mangatia Paolo , Cringoli Maurizio , Blanca Deborah , Casella Francesco , Vegetti Alberto , Crociani Andrea , Donnarumma Emilia , Pacciani Giulia , Rovereto Rossella , Lunardi Sarah , Tufano Antonella , Pacetti Veronica , Domenicali Marco , Leopoldo Pier , Ceci Fabrizio 
Published: December 2022

Abstract
Background
Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear.

Objectives
To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge.

Patients/Methods
In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score.

Results
Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6–15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events.

Conclusions
We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission.

Trial registration
NCT03157843.