ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022
ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022
ABSTRACT
Background: Severe coronavirus disease 2019 (COVID-19) is associated with inflammatory cytokine burst and coagulopathy. Platelets may contribute to microthrombosis development and be a target in COVID-19 therapy. Aim(s): To determine the significance of platelet activation and antiplatelet agents (APAs) treatment in COVID-19 pathophysiology and mortality in two cohorts of patients with COVID-19. Method(s): We explored two cohorts of COVID-19 patients: Cohort A (NCT04624997) included 208 ambulatory and hospitalized patients of different clinical severity with evaluation of soluble CD40 ligand (sCD40L) and P-selectin (sP-sel) plasma levels of within the first 48 hours following admission. Cohort B included 2878 patients initially admitted in medical ward with collection of clinical characteristics and outcomes (NCT04344327). In both cohorts, the primary outcome was in-hospital mortality. Result(s): In cohort A, circulating median levels of sCD40L and sP-sel were significantly increased solely in critical patients with COVID-19 (sP-sel: 40059 pg/ml, IQR 26876-54678;sCD40L: 1914 pg/ml IQR 1410-2367;p < 0.001 for both), signaling platelet hyper-activation. However, pre-hospitalization APAs did not significantly modified sCD40L and sP-sel levels. Admission sP-sel levels were predictive in-hospital mortality (Kaplan-Meier log-rank p = 0.004), even after adjustment on CRP, while adjustment on D-dimer abolished this relationship, suggesting that platelet activation is highly interrelated with coagulopathy. We confirmed this finding in a Cox model adjusted for age, sex, CRP and D-dimer levels (Odds ratio 1.78, 95% CI 0.63-4.50). We confirmed in cohort B (2878 patients) that, among patients receiving APA before hospitalization, there was no significant difference in the proportion of death in a Cox model (Hazard ratio 1.0, IQR0.77-1.30) adjusted for demographic comorbidities. Conclusion(s): Our findings highlight the critical role of coagulopathy, in contrast to platelet activation, in discriminating COVID-19 severity and increased risk of in-hospital mortality. We also confirm that APAs before hospitalization do not influence neither mortality nor platelet activation. (Table Presented).
ABSTRACT
Background: Concerns emerged for the management of intramuscular (IM) injections for COVID-19 vaccines in patients with therapeutic anticoagulation. Aim(s): The aim of the study was to evaluate the risk of bleeding events following IM vaccination in patients under therapeutic anticoagulation Methods: We first performed a French multicentre prospective study including patient treated by anticoagulant therapy for venous thromboembolism between May 2021 and September 2021. Consecutive patients were asked to report bleeding events at the site of COVID-19 vaccine injection during follow-up. We next performed a request in the French national pharmacovigilance database to identify cases of bleeding events at the site of injections following COVID-19 vaccine in patients under therapeutic anticoagulation between December, 27th, 2020 and June, 30th, 2021. Result(s): Between May and September 2021, a total of 348 patients with anticoagulant therapy received 561 IM injections of COVD-19 vaccines. Median age of patients was 68.4 years and 65.2% were males. Almost all patients were treated with direct oral anticoagulant (DOAC 96.6%), 11 (3.2%) patients with vitamin K antagonist and one (0.2%) with tinzaparin. Among them, 17.9% had pressure at the injection site after the injection and 4.2% had anticoagulant dose skipping before vaccination. After IM injections, a total of 3 (0.6%) bleeding events were observed, 2 (0.4%) minor and one (0.2%) clinically relevant non-major bleeding. We next observed in the French national pharmacovigilance database a total of 13 bleeding events (all minor bleeding) at the site of injection in patients on therapeutic anticoagulation between December, 27th, 2020 and June, 30th, 2021. In France, 69,089,410 doses of COVID-19 vaccine were administered during this period. These bleeding events correspond to a spontaneous notification rate of 0.19 cases (95% CI 0.09-0.29) reported per million of doses administered. Conclusion(s): IM vaccination appears safe in patients under therapeutic anticoagulation in particular with DOAC, and may not require skipping doses.
ABSTRACT
Background : D-dimer is a safe tool to exclude pulmonary embolism (PE) but its specificity is decreased in COVID-19. Aims : Our aim was to derive a new algorithm with D-dimer threshold adjusted to CT extent of lung damage. Methods : We conducted a multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to CT extent of lung damage was derived in a patient set ( n = 337), and its safety assessed in an independent validation set ( n = 337). Results : According to ROC curves, D-dimer safely excluded PE, with one false negative when using a 900 ng/mL threshold when lung damage extent was <50% and 1700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm's sensitivity was 98.2% (95% CI: 94.7-100.0), and its specificity 28.4% (95% CI: 24.1-32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01-0.44) and the AUC was 0.63 (95% CI: 0.60-0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7-99.6) and 39.2% (95% CI: 32.2-46.1), respectively. The NLR was 0.08 (95% CI: 0.02-0.33), and the AUC did not differ from that of the derivation set (0.68 (95% CI: 0.64-0.72), P = 0.097). Using the Co-LEAD algorithm, 76/250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA). Conclusions : The Co-LEAD algorithm safely excludes PE, and allows reducing the use of CTPA in COVID-19 patients. Prospective management studies are necessary to validate this strategy.
ABSTRACT
Background : High rates of venous thromboembolic events associated to LMWH/heparin therapy lead to numerous heparin-induced thrombocytopenia (HIT) suspicion during COVID-19 outbreak. Aims : We aim to describe HIT-suspected patient's characteristics and prevalence between March 15 and April 15 of 2020. Methods : This is a multi-centric retrospective cohort study of HITsuspected patients referred to our center. 4T score has been realized by experienced hematologist and/or pharmacologist and allowed us to trigger specific HIT assays if score was >3 (IgG anti-PF4/H and 14C-serotonine release assay, SRA). We included all consecutive HIT-suspected patients during COVID-19 outbreak compared to the same period in 2019. Results : During 2019 and 2020-study periods we identified, respectively, 17 and 41 consecutive HIT-suspected patients. Among the 2020-group, 23 were COVID-19 and 18 were non-COVID-19 patients. Clinical and biological characteristics were not significantly different between the 2019, 2020 non-COVID-19 and COVID-19 HIT-suspected patients. During 2019-period study, 11 (64.7%) patients had a 4T score >3, 4 (36.3%) of them had positive anti-PF4/H antibodies and only one had a positive SRA assay. During 2020-period study, 8 (44.4%) non-COVID-19 and 10 (43.5%) COVID-19 patients had a 4T score >3. Among them, respectively, 3 (37.5%) and 3 (30.%) had positive anti-PF4/H antibodies. SRA assay was positive in 3 non-COVID-19 patients tested and in the only one COVID-19 tested patient. The 4T score was able to exclude HIT in 67% of COVID-19 patients suspected. In 2020-study period, when comparing COVID-19 and non-COVID-19 patients, the only significantly difference in term of HIT suspicion criteria was the mean duration of heparin exposition before suspicion: 9.9 days ±6.3 for non-COVID-19 patients versus 15.2 days ±8.8 for COVID-19 patients, P = 0.043). Conclusions : HIT suspicion in COVID-19 occurs after longer anticoagulation time than non-COVID-19. We did not observe more confirmed HIT in COVID-19 in contrast our two non-COVID-19 control groups.
ABSTRACT
Background : Antiphospholipid antibodies (APA) clinical relevance in COVID-19 is controversial. Aims : We aimed to investigate the prevalence and prognostic value of conventional and non-conventional APA in COVID-19 patients. Methods : This study was a multi-centric, prospective observational French cohort of patients hospitalized for COVID-19 suspicion. Results : 249 patients were hospitalized for suspected COVID-19, including 154 (61.8%) with confirmed COVID-19 and 95 (38.2%) not confirmed. We found a significant increase in lupus anticoagulant (LA) positivity among COVID-19 positive patients (60.9% versus 23.7% in non-COVID19 patients, P < 0.001), while prevalence of conventional (LA, IgG, IgM and IgA isotypes) and non-conventional APA (anti-phosphatidylserine/prothrombin IgG and IgM) were low in both groups. COVID-19 patients with LA positivity had higher levels of fibrinogen (6.0 g/L, IQR 5.0-7.0 versus 5.3 IQR 4.3-6.4, P = 0.028) and C-reactive protein (CRP, 115.5 IQR 66.0-204.8 versus 91.8 mg/L, IQR 27.0-155.1, P = 0.019). Univariate analysis did not show any association between LA positivity and higher risk of venous thromboembolism (VTE, OR 1.02, 95% CI 0.44-2.43, P = 0.95) or inhospital mortality (OR 1.80, 95% CI 0.70-5.05, P = 0.24). Unadjusted and adjusted (to CRP, age and sex) Kaplan-Meier survival curves according to LA positivity confirmed the absence of association with VTE or in-hospital mortality (unadjusted: P = 0.64 and P = 0.26, respectively;adjusted: hazard ratio = 1.13 95% CI 0.48-2.60 and 1.80 95% CI 0.67-5.01). Conclusions : COVID-19 patients have an increased prevalence of LA positivity associated with biological inflammation markers. However, positive LA at admission is not associated with VTE risk and/or inhospital mortality.