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Circulating endothelial progenitor cells (EPCs) were first described in 1997 by Asahara et al. as "putative endothelial cells" from human peripheral blood. The study of endothelial progenitors is also intensifying in several pathologies associated with endothelial damage, including diabetes, myocardial infarction, sepsis, pulmonary arterial hypertension, obstructive bronchopneumopathy and transplantation. EPCs have been studied in several autoimmune diseases with endothelial involvement such as systemic lupus erythematosus, thrombotic thrombocytopenic purpura, antineutrophil cytoplasmic antibodies, vasculitis, rheumatoid arthritis, Goujerot-Sjögren and antiphospholipid syndrome. Factors involved in endothelial damage are due to overexpression of pro-inflammatory cytokines and/or autoantibodies. Management of these pathologies, particularly the long-term use of glucocorticoids and methotrexate, promote atherosclerosis. A lack of standardized assessment of the number and function of EPCs represents a serious challenge for the use of EPCs as prognostic markers of cardiovascular diseases (CVD). The objective of this review was to describe EPCs, their properties and their involvement in several autoimmune diseases. [ABSTRACT FROM AUTHOR]

Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between 0.3 and 0.7 U/mL. Correlation among aPTT, anti-Xa activity, and thrombin generation was determined by measuring endogenous thrombin potential (ETP), with the inflammatory response evaluated. C-reactive protein (CRP) was used as a marker of inflammatory response. The plasma of 107 samples from 30 ICU patients was analyzed. The correlation between aPTT and anti-Xa activity was 0.66, CI95% [0.54;0.76] (p < 0.0001). Although thrombin generation, aPTT, and anti-Xa were correlated with inflammatory responses, the correlation was higher with thrombin generation and anti-Xa activity compared to aPTT. When aPTT was in a therapeutic range, a low thrombin generation was observed but was 50% inhibited when anti-Xa was in a therapeutic range. Coagulation testing with aPTT, anti-Xa correlated with thrombin generation. A 50% decrease in thrombin generation was observed when anti-Xa was within a therapeutic range. Further work is needed to evaluate coagulation biomarker responses and clinical outcomes in specific ICU populations. [ABSTRACT FROM AUTHOR]

Indeed, risk and severity of bleeding are correlated with the fibrinogen level but a fibrinogen level >1 g/l is usually sufficient to protect from spontaneous bleeding or caused by minor trauma.1 This is the case of parents in our study. Keywords: bleeding; cephalhaematoma; hereditary afibrinogenemia EN bleeding cephalhaematoma hereditary afibrinogenemia e641 e644 4 09/16/21 20210901 NES 210901 DATA AVAILABILITY STATEMENT Data sharing not applicable to this article as no datasets were generated or analysed during the current study. The keystone of treatment of severe fibrinogen deficiency is the replacement therapy with fibrinogen to prevent the bleeding risk. [Extracted from the article]

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive and irreversible lung disease constantly associated with a major vascular remodeling process. Endothelial colony-forming cells (ECFCs) are human vasculogenic cells proposed as a cell therapy product or liquid biopsy in vascular disorders. Since the link between IPF and thrombosis has been largely proposed, the aim of our study was to explore hypercoagulability states in ECFCs from patients with IPF. We performed Thrombin generation assay (TGA) in cord blood (CB)-ECFCs, peripheral blood (PB)-ECFCs and IPF-ECFCs. Endogenous thrombin potential and peak were higher in IPF-ECFCs compared to CB-ECFCs and PB-ECFCs. As thrombin generation in ECFCs was increased, we evaluated anticoagulant proteins expressed on ECFCs membrane and identified thrombomodulin and EPCR. We found a significant decrease of both anticoagulant proteins at membrane using flow cytometry. This study is the first to examine ECFC thrombin generation in IPF. This new finding strongly argues for a role of ECFC in IPF pathophysiology and thrombotic related disorders in IPF. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by recurrent venous or arterial thrombotic events and pregnancy morbidity, with persistently presence of antiphospholipid antibodies (aPL). We report three cases of central serous chorioretinopathy (CSC) associated with APS. [ABSTRACT FROM AUTHOR]

Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be present in 18%. Thrombin generation test is commonly used as an evaluation tool of thrombotic risk. The objective of this study was to evaluate the thrombogenic potential of FVL in asymptomatic carriers and in patients with personal or familial history of thrombosis. This was a retrospective single center study including 160 patients. Among them, 43 had personal history of thrombosis and 117 had familial history of thrombosis. Thrombin generation (TG) was realized in frozen platelet poor plasma with 1 pM of tissue factor and 4 µM of phospholipid. FVL mutation was associated with a global increase of TG. No difference was observed between patients with provoked thrombosis and patients with first-degree familial history of thrombosis (endogenous thrombin potential (ETP): 1501.0 ± 316.4 nM min and thrombin peak: 253.4 ± 71.5 nM vs. 1520.4 ± 283.8 nM min and 268.6 ± 68.0 nM). An increase of TG was observed in patients with unprovoked thrombosis (n = 23) and in patients with provoked thrombosis (n = 20) (ETP: 1819.5 ± 319.8 nM min and peak: 332.3 ± 55.8 nM). In the unprovoked thrombosis group, patients with a pulmonary embolism had a higher ETP than patients with deep vein thrombosis (DVT) (2036 ± 343 nM min vs. 1707 ± 261 nM min). With a predictive score formula (s = 0.1315 × Age + 0.0105 × ETP) with a threshold of 22.1 as risk to develop an unprovoked thrombosis among patients with second-degree familial history. The results of our analysis suggest that measurement of thrombin generation in patients with FVL mutation may identify subjects with an increased risk of unprovoked thrombosis. Further studies are needed to examine the usefulness of predicting thrombotic presentation in asymptomatic carriers. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) promote endothelial dysfunction, inflammation and procoagulant state. We investigated the effect of hydroxychloroquine (HCQ) on prothrombotic state and endothelial function in mice and in human aortic endothelial cells (HAEC). Human aPL were injected to C57BL/6 mice treated or not with HCQ. Vascular endothelial function and eNOS were assessed in isolated mesenteric arteries. Thrombosis was assessed both in vitro by measuring thrombin generation time (TGT) and tissue factor (TF) expression and in vivo by the measurement of the time to occlusion in carotid and the total thrombosis area in mesenteric arteries. TGT, TF, and VCAM1 expression were evaluated in HAEC. aPL increased VCAM-1 expression and reduced endothelium dependent relaxation to acetylcholine. In parallel, aPL shortened the time to occlusion and extended thrombus area in mice. This was associated with an overexpression of TF and an increased TGT in mice and in HAEC. HCQ reduced clot formation as well as TGT, and improved endothelial-dependent relaxations. Finally, HCQ increased the p-eNOS/eNOS ratio. This study provides new evidence that HCQ improves procoagulant status and vascular function in APS by modulating eNOS, leading to an improvement in the production of NO. [ABSTRACT FROM AUTHOR]

Background: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. Materials: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. Results: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4–12.5] vs. 12.3 [8.3–20.7], p = 0.02) while fibrinogen (6.9 [6.1–7.7] vs. 6.2 [5.4–6.9], p = 0.03), vWF-GpIb (286 [265–389] vs. 268 [216–326], p = 0.03) and F1 + 2 (226 [151–578] vs. 155 [129–248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06–1.17] and OR = 0.47 [0.25–0.76] respectively). The association of a SAPS-II ≥ 33 and an A-IPC ≤ 12.6 G/L predicted the worsening of patients (sensitivity 58%, specificity 89%). Conclusions: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is associated with thrombotic events (tAPS) and/or obstetrical morbidity (oAPS), with persisting antiphospholipid antibodies (aPL). Despite an update of aPL in 2006, several patients had typical clinical events without the classical biological criteria. The aim of our study was to evaluate the hypercoagulability state with both thrombin generation (TG) profiles and activated protein C resistance (aPCR) in different types of APS. Methods: We retrospectively included 41 patients with Sydney criteria classification (tAPS, oAPS) and no clinical manifestation of APS with persistent aPL (biological APS). A thrombin generation assay was performed with a Fluoroskan Ascent fluorometer in platelet-poor plasma (PPP). Activated protein C resistance was measured as a ratio: ETP+aPC/ETP-aPC × 100. Results: Thrombotic APS and oAPS had an increase of global thrombin generation (ETPcontrol = 808 nM.min (756–853) vs. 1265 nM.min (956–1741) and 1863 nM.min (1434–2080), respectively) (Peakcontrol = 78 nM (74–86) vs. 153 nM (109–215) and 254 nM.min (232–289), respectively). Biological APS had only a lag time increase (Tcontrol = 4.89 ± 1.65 min vs. 13.6 ± 3.9 min). An increased aPCR was observed in tAPS (52.7 ± 16.4%), oAPS (64.1 ± 14.6%) as compared to the control group (27.2 ± 13.8%). Conclusion: Our data suggest an increase of thrombin generation in thrombotic and obstetrical APS and no hypercoagulable states in patients with biological APS. The study of a prospective and a larger controlled cohort could determine the TGA useful for APS monitoring and could confirm an aPCR evaluation in PPP. [ABSTRACT FROM AUTHOR]

• Red blood cell disorders are associated with hypercoagulability state. • Thrombin generation assay evaluates hypercoagulability. • All red blood cell disorders reported hypercoagulability on peak and velocity. • Splenectomy is associated with hypercoagulability in hereditary spherocytosis. • Co-inherited α-thalassemia with sickle cell trait decreased hypercoagulability. [ABSTRACT FROM AUTHOR]

In patients with severe haemophilia receiving clotting factor concentrates, the risk of immunisation against their usual treatment is still patent and feared. New haemophilia drug treatments with an extended half-life have become available over the past few years. The risk of inhibitor development to these new treatments is unclear. We report the case of a 51-year-old man with severe haemophilia A, who was previously treated with no history of inhibitor development. Soon after a switch in his treatment to efmoroctocog alfa he developed an inhibitor against this recombinant Fc fusion extended half-life FVIII (rFc-FVIII) product. The patient was on an on-demand treatment regimen and was treated for mucosal bleeding. The inhibitor was characterised as type I, with classical epitope mapping. The spontaneous evolution of this inhibitor was favourable, but an anamnestic response led to a switch in his treatment to emicizumab. [ABSTRACT FROM AUTHOR]