Prévention du risque thromboembolique veineux et surveillance de l’hémostase chez les patients hospitalisés pour COVID-19 : propositions réactualisées (avril 2021). Groupe d’intérêt en hémostase périopératoire (GIHP) et groupe d’étude sur l’hémostase et la thrombose (GFHT) Prevention of venous thromboembolism and haemostasis monitoring in patients with COVID-19: Updated proposals (April 2021): From the French working group on perioperative haemostasis (GIHP) and the French study group on thrombosis and haemostasis (GFHT), in collaboration with the French society of anaesthesia and intensive care (SFAR)

<h4>Contexte</h4> La COVID-19 est associée à un risque thromboembolique veineux élevé, en particulier chez les patients sévères. Depuis les premières propositions GIHP/GFHT publiées en avril 2020, de nouvelles connaissances sont apparues. L’objet du présent travail était de réactualiser ces propositions. <h4>Méthodes</h4> Un groupe de travail a défini sept questions et effectué une revue critique de la littérature. Les propositions ont été formulées après consensus entre les membres du groupe de travail et les autres membres du GIHP/GFHT. <h4>Résultats</h4> Chez les patients hospitalisés non sévères et certains patients ambulatoires à risque, nous suggérons l’administration d’une thromboprophylaxie à dose standard. Chez les patients sévères, nous suggérons une thromboprophylaxie à dose intermédiaire ou thérapeutique selon le taux de D-dimères et son évolution. Sept à dix jours après l’admission, nous suggérons de revenir à une dose standard pour réduire le risque hémorragique. Chez les patients présentant un très haut risque thrombotique, ayant reçu une thromboprophylaxie à dose thérapeutique, nous suggérons un dépistage systématique de la thrombose avant la désescalade. Nous suggérons d’ajuster l’anticoagulation au poids des patients. Nous suggérons un monitorage régulier des paramètres d’hémostase, incluant les D-dimères, chez les patients sévères. Nous suggérons un monitorage de l’anticoagulation à dose intermédiaire et thérapeutique par l’activité anti-Xa. <h4>Conclusion</h4> Les propositions réactualisées suivent une approche standard de la thromboprophylaxie, visant à diminuer l’incidence des évènements thromboemboliques veineux symptomatiques. Chez les patients sévères, nous proposons une stratégie séquentielle tenant compte de la relation temporelle entre le risque thrombotique et le risque hémorragique.

Prévention du risque thromboembolique veineux et surveillance de l’hémostase chez les patients hospitalisés pour COVID-19 : propositions réactualisées (avril 2021). Groupe d’intérêt en hémostase périopératoire (GIHP) et groupe d’étude sur l’hémostase et la thrombose (GFHT)

Résumé Contexte La COVID-19 est associée à un risque thromboembolique veineux élevé, en particulier chez les patients sévères. Depuis les premières propositions GIHP/GFHT publiées en avril 2020, de nouvelles connaissances sont apparues. L’objet du présent travail était de réactualiser ces propositions. Méthodes Un groupe de travail a défini sept questions et effectué une revue critique de la littérature. Les propositions ont été formulées après consensus entre les membres du groupe de travail et les autres membres du GIHP/GFHT. Résultats Chez les patients hospitalisés non sévères et certains patients ambulatoires à risque, nous suggérons l’administration d’une thromboprophylaxie à dose standard. Chez les patients sévères, nous suggérons une thromboprophylaxie à dose intermédiaire ou thérapeutique selon le taux de D-dimères et son évolution. Sept à dix jours après l’admission, nous suggérons de revenir à une dose standard pour réduire le risque hémorragique. Chez les patients présentant un très haut risque thrombotique, ayant reçu une thromboprophylaxie à dose thérapeutique, nous suggérons un dépistage systématique de la thrombose avant la désescalade. Nous suggérons d’ajuster l’anticoagulation au poids des patients. Nous suggérons un monitorage régulier des paramètres d’hémostase, incluant les D-dimères, chez les patients sévères. Nous suggérons un monitorage de l’anticoagulation à dose intermédiaire et thérapeutique par l’activité anti-Xa. Conclusion Les propositions réactualisées suivent une approche standard de la thromboprophylaxie, visant à diminuer l’incidence des évènements thromboemboliques veineux symptomatiques. Chez les patients sévères, nous proposons une stratégie séquentielle tenant compte de la relation temporelle entre le risque thrombotique et le risque hémorragique.

Daily Telephone Call During the COVID-19 Pandemic: Perceptions of Families and Providers.

BACKGROUND: In intensive care units (ICUs), the quality of communication with families is a key point in the caregiver-patient-family relationship. During the COVID-19 pandemic, hospital visits were prohibited, and many ICUs implemented a daily telephone call strategy to ensure continuity of communication with patients' families. OBJECTIVE: To assess how family members and health care providers perceived this communication strategy. METHODS: The study was conducted in a 45-bed ICU during the COVID-19 pandemic. Communication with families consisted of a single daily telephone call from the senior physician in charge of the patient to the patient's surrogate decision maker. Satisfaction was qualitatively assessed via an anonymous online questionnaire with open-ended questions. RESULTS: Participants completed 114 questionnaires. Forty-six percent of surrogate decision makers stated that the key medical messages were understandable, but 57% of other family members expressed that the frequency of information delivery was insufficient. Fifty-six percent of the physicians described the practice as functional for the organization of the unit. Among health care providers other than physicians, 55% felt that not having to interact with families decreased their emotional load and 50% mentioned saving time and the absence of task interruptions as positive aspects. CONCLUSION: Fixed-time, daily telephone calls in the ICU allowed satisfactory transmission of information between physicians and surrogate decision makers, as perceived by both parties. However, the telephone-based communication strategy could still be improved.

Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With COVID-19 Pneumonia.

BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov.

Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Single-Center Study.

BACKGROUND AND OBJECTIVES: Kidney involvement is frequent among patients with coronavirus disease 2019 (COVID-19), and occurrence of AKI is associated with higher mortality in this population. The objective of this study was to describe occurrence and significance of proteinuria in this setting. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS : We conducted a single-center retrospective study to describe the characteristic features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France, and to evaluate its association with initiation of dialysis, intensive care unit admission, and death. RESULTS: Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75-1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50-410), with a urine albumin-protein ratio <50% in 92% of patients. Urine retinol binding protein concentrations, available for 85 patients, were ≥0.03 mg/mmol in 62% of patients. Urine protein-creatinine ratio ≥1 g/g was associated with initiation of dialysis (odds ratio, 4.87; 95% confidence interval, 2.03 to 13.0; P<0.001), admission to the intensive care unit (odds ratio, 3.55; 95% confidence interval, 1.93 to 6.71; P<0.001), and death (odds ratio, 3.56; 95% confidence interval, 1.90 to 6.54; P<0.001). CONCLUSIONS: Proteinuria is very frequent among patients admitted for COVID-19 and may precede AKI. Low levels of albuminuria suggest a predominant tubular origin, confirmed by the elevated levels of urine retinol binding protein. Urine protein-creatinine ratio ≥1 g/g at admission is strongly associated with poor kidney and patient outcome.

Major bleeding complications in critically ill patients with COVID-19 pneumonia.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring.

COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted.In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19.Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m2, no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 µg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed.In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.