Fig. 1. Lupus anticoagulant (LA) results in COVID-19 patients with (black circles) and without thrombotic events (open squares). Patient dRVVT screen (Scr, low phospholipid concentration) and confirm (Conf, high phospholipid concentration) results were normalized, i.e. expressed as ratios against reference plasma results.Final results were expressed as screen ratio/confirm ratio. Cut-off value was 1.20 for both screen ratio and screen ratio/confirm ratio, demonstrating the phospholipodependence.

Introduction: Lupus Anticoagulant (LA) testing using dilute Russell Viper Venom Time (dRVVT) is challenging in patients receiving Direct Oral AntiCoagulants (DOAC) due to potential false positive results. In a multicenter study, we evaluated the in vitro removal of DOAC by activated charcoal (DOAC remove ®), allowing reliable dRVVT testing. Materials and Methods: Patient samples were analyzed before and after treatment with DOAC remove ® : 49 apixaban, 48 rivaroxaban, 24 dabigatran and 30 none. DOAC plasma concentrations were measured using anti-Xa or anti-IIa diluted thrombin time assays. In a subset of 28 samples, DOAC concentrations were also measured using HPLC-MS/MS following treatment with DOAC remove ®. DRVVT was performed using STA-Staclot dRVVT Screen ® /Confirm ® (Stago) or LAC-Screening ® /Confirm ® (Siemens). Results: Baseline median [min-max] concentrations were 94 [<20-479] for apixaban, 107 [<20-501] for rivaroxaban and 135 ng/mL [<20-792] for dabigatran; dRVVT screen ratio /confirm normalized ratio was positive in 47, 90 and 42 % of apixaban, rivaroxaban and dabigatran samples. Treatment with DOAC remove ® did not affect dRVVT results in non-DOAC patients while it resulted in DOAC concentrations < 20 ng/mL in 82, 98 and 100 % of samples, respectively. Concentrations were < 5 ng/mL with HPLC-MS/MS in 5 out of 10, 8 out of 10 and 7 out of 8 samples, respectively. DOAC remove ® corrected DOAC interference with dRVVT assays allowed excluding LA in 76, 85 and 95 % of the patients, respectively. without affecting dRVVT results in non-DOAC patients. Conclusion: For dRVVT testing in DOAC patients, we suggest the use of DOAC remove ® for every rivaroxaban sample, whereas it might only be used in positive apixaban and dabigatran samples. A residual DOAC interference cannot be ruled out in case of persisting dRVVT positive results after treatment with DOAC remove ®. For those with persisting positive results, LA-diagnosis using dRVVT remains questionable.

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The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55–77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6–4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1–537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4–29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5–67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.

Background A high prevalence of pulmonary embolism (PE) has been described during COVID‐19. Our aim was to identify predictive factors of PE in non‐ICU hospitalized COVID‐19 patients. Methods Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID‐19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. Results A total of 88 patients (median [IQR] age of 68 years [60‐78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D‐dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3‐74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3‐1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7‐553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D‐dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0‐397.9], P = .004). Conclusion The white blood count, the D‐dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non‐ICU COVID‐19 patients.

Background: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions and polypharmacy, receive direct oral anticoagulants (DOAC), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. Aims: To investigate: i/DOAC concentration-time profiles; ii/thrombin generation (TG); and iii/clinical outcomes 6-months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. Methods: ADAGE-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged 80-years, receiving DOAC for at least 4 days. Each patient had 1-5 blood samples at different time-points over 20-days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). Results: We included 215 patients (women 71.1%, mean age 87±4-years), 104-rivaroxaban and 111-apixaban, 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (CV) whatever the regimen, at Cmax [49-46%] and Cmin [75-61%] in 15mg-rivaroxaban and 2.5mg-apixaban patients, respectively. Dose regimen was associated with Cmax and Cmin plasma concentrations in apixaban (p=0.0058 and p=0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak-height (STG-Thromboscreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thrombo-embolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. Conclusion: Our study provides original data in very elderly patients receiving DOAC in real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal disease in the absence of treatment, which consists of daily therapeutic plasma exchange (TPE), in association with cortico-CORRESPONDENCE E29