Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.

SummaryBackground. The outbreak of chilblain‐like lesions (CLL) during the COVID‐19 pandemic has been reported extensively, potentially related to SARS‐CoV‐2 in

Summary: Endothelial colony-forming cells (ECFCs) are progenitor cells committed to endothelial lineages and have robust vasculogenic properties. Mesenchymal stem cells (MSCs) have been described to support ECFC-mediated angiogenic processes in various matrices. However, MSC-ECFC interactions in hind limb ischemia (HLI) are largely unknown. Here we examined whether co-administration of ECFCs and MSCs bolsters vasculogenic activity in nude mice with HLI. In addition, as we have previously shown that endoglin is a key adhesion molecule, we evaluated its involvement in ECFC/MSC interaction. Foot perfusion increased on day 7 after ECFC injection and was even better at 14 days. Co-administration of MSCs significantly increased vessel density and foot perfusion on day 7 but the differences were no longer significant at day 14. Analysis of mouse and human CD31, and in situ hybridization of the human ALU sequence, showed enhanced capillary density in ECFC+MSC mice. When ECFCs were silenced for endoglin, coinjection with MSCs led to lower vessel density and foot perfusion at both 7 and 14 days (p<0.001). Endoglin silencing in ECFCs did not affect MSC differentiation into perivascular cells or other mesenchymal lineages. Endoglin silencing markedly inhibited ECFC adhesion to MSCs. Thus, MSCs, when combined with ECFCs, accelerate muscle recovery in a mouse model of hind limb ischemia, through an endoglindependent mechanism.Supplementary Material to this article is available online at www.thrombosis-online.com.

Background: Coronavirus disease 2019 (COVID‐19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID‐19. Methods and Results: Patients with COVID‐19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in‐hospital mortality). The study enrolled 2878 patients with COVID‐19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55–0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29–0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61–0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low‐ or high‐dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions: Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID‐19–associated coagulopathy and endotheliopathy, and lead to a better prognosis.

Background Coronavirus disease 2019 (COVID‐19) is a respiratory disease associated with vascular inflammation and endothelial injury. Objectives Correlate circulating angiogenic markers VEGF‐A, PlGF and FGF‐2 to in‐hospital mortality in COVID‐19 adult patients. Methods Consecutive ambulatory and hospitalized patients with COVID‐19 infection were enrolled. VEGF‐A, PlGF and FGF‐2 were measured in each patient ≤48 h following admission. Results Study enrolled 237 patients with suspected COVID‐19: 208 patients had a positive diagnostic for COVID‐19 of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF‐A, PlGF and FGF‐2 significantly increase with the severity of the disease (p<0.001). Using a logistic regression model we found a significant association between the increase of FGF‐2 or PlGF and mortality (OR 1.11, 95% CI [1.07–1.16], p<0.001 for FGF‐2 and OR 1.07 95% CI [1.04–1.10], p<0.001 for PlGF) while no association were found for VEGF‐A levels. ROC curve analysis was performed and we identified PlGF above 30 pg/mL as the best predictor of in‐hospital mortality in COVID‐19 patients. Survival analysis for PlGF confirmed its interest for in‐hospital mortality prediction, by using a Kaplan‐Meier survival curves (p=0.001) and a Cox proportional hazard model adjusted to age, body mass index, D‐dimer and CRP (3.23 95% CI [1.29–8.11], p=0.001). Conclusion Angiogenic factor PlGF is a relevant predictive factor for in‐hospital mortality in COVID‐19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID‐19.