Characteristics of deep vein thrombosis in the critically ill COVID-19 patient - an observational cohort study with Doppler ultrasound measurements.

OBJECTIVE: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients. PATIENTS AND METHODS: We conducted a prospective single-center cohort study in March-October 2020 including all consecutive mechanically ventilated COVID-19 adults. Doppler ultrasound of the lower limbs was performed systematically during the first week of hospitalization. In DVT-free patients, a second Doppler ultrasound was performed seven days later. Data are expressed as medians (interquartile ranges) or percentages. Comparisons were performed using Mann-Whiney and Wilcoxon signed-rank tests or Fischer's exact tests, as appropriate. RESULTS: Fifty-five patients [age, 63 years (56-74); female/male ratio, 0.62; body-mass index, 29 kg/m2 (26-33); hypertension, 47%; diabetes, 38%; ischemic heart disease, 11%] were included. DVT was diagnosed in 19 patients (35%) including in 5 femoral (9%), 2 popliteal (4%) and 12 below-the-knee sites (22%). CFV diameter was increased to 12.0 mm (11.0-15.0) (normal range, 9.1-12) and PBFV reduced to 11.9 cm/s (8.8-15.8) (normal range, 21.3-49.2) [right-side values]. In four patients who had ultrasound before intubation, CFV diameter increased from 12.5 mm (11.8-13.3) before to 14 mm (13.6-15.3) after intubation (p = 0.008). CONCLUSIONS: DVT in the CFV occurred in 9% of the critically ill COVID-19 patients with an overall 35%-DVT prevalence. Venous return difficulty evidenced by larger than normal CFV diameters and lower than normal PBFVs may have facilitated proximal DVT occurrence.

Étude prospective des événements thromboemboliques veineux chez les patients hospitalisés pour COVID-19 : anomalies associées de l’hémostase et suivi clinicobiologique à 6 mois

Introduction La COVID-19 est associée à un risque élevé d’événement thromboembolique veineux (ETEV), thrombose veineuse profonde (TVP) et/ou embolie pulmonaire (EP) en particulier chez les patients hospitalisés. Objectifs Caractériser le déséquilibre de la balance hémostatique chez ces patients et décrire la prise en charge et l’évolution à 6 mois des patients avec ETEV. Méthodes Étude prospective incluant des patients consécutifs hospitalisés en réanimation ou en médecine pour COVID-19, avec : – un écho-Doppler veineux systématique à l’admission en réanimation puis 7jours plus tard en cas de négativité et en cas de symptômes de TVP en service de médecine ;– un angioscanner thoracique réalisé en cas de suspicion d’EP ;– un bilan d’hémostase réalisé à l’admission ;– le suivi des patients ayant présenté un ETEV à 1, 3 et 6 mois afin de colliger les événements thrombotiques et hémorragiques. Résultats Du 17.03 au 11.04.2020, 133 patients d’âge médian 65 ans (72 % hommes) ont été hospitalisés pour COVID-19. Trente-huit patients ont présenté un ETEV (63 % TVP, 24 % EP, 13 % TVP+EP) dont 9 sont décédés pendant l’hospitalisation, 2 ont été transférés et 26 suivis. Nos résultats montrent : – un taux de D-dimères>3300ng/mL prédictif d’un ETEV avec une VPP 66 % (IC95 % : 51–79) et VPN 80 % (IC95 % : 65–90) en réanimation ;– une discordance significative entre les activités anticoagulante/chromogénique de la protéine C (p=.002 chez les patients ETEV+) évocatrice d’une résistance acquise à la protéine C activée ;– une association entre les taux de facteur Willebrand et d’ADAMTS13 et les ETEV (p=.05 et p=.005 respectivement) d’une part et entre les taux d’ADAMTS13/D-dimères et la mortalité d’autre part ;– des anticorps antiphospholipides présents chez 88 % des patients en réanimation, non associés à la survenue d’ETEV. Les 26 patients suivis avec ETEV ont été traités par apixaban (22), rivaroxaban (2) ou tinzaparine (2) durant 3 à 6 mois. Un infarctus du myocarde et 2 saignements mineurs ont été recensés. Aucune récidive d’ETEV n’a été observée. Conclusions La fréquence élevée d’ETEV chez les patients hospitalisés pour COVID-19 est associée à un profil biologique de thrombo-inflammation, avec un déséquilibre marqué entre facteurs prothrombotiques/inhibiteurs naturels de la coagulation et de l’axe VWF/ADAMTS13. Le traitement par anticoagulant oral direct est une option thérapeutique possible pour le traitement d’un ETEV lié à une hospitalisation pour COVID-19.

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

OBJECTIVES: The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis. METHODS: We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise. RESULTS: Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for >=3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01). CONCLUSION: IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.

Deep vein thrombosis in patients with covid-19 pneumonia

Patients with Covid-19 pneumonia are predisposed to thromboembolic complications due to a hypercoagulable state and endotheliopathy. This mini-review analyzes the main studies regarding deep vein thrombosis and its prevalence which ranges in intensive care patients from 46 % to 86 % according to the studied patients, the type of thromboprophylaxis administered and the number of doppler ultrasound examinations performed during the hospital stay to establish the diagnosis of thrombosis. The implications for clinical practice, and therapeutic perspectives are discussed. Randomized studies comparing several anticoagulation strategies are underway and will enable in the close future therapeutic choices optimizing the risk/benefit ratio. © 2020, John Libbey. All rights reserved.

Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.

OBJECTIVE: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE). PATIENTS AND METHODS: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis. RESULTS: Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001]. CONCLUSIONS: Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.