Association between coagulation activity and clinical and imaging outcomes in acute ischemic stroke patients - A sub-study of the MR CLEAN NO-IV trial.

Background: The MR CLEAN NO-IV trial showed neither superiority nor noninferiority of endovascular treatment (EVT) alone compared to intravenous thrombolysis (IVT; Alteplase) before EVT in acute ischemic stroke (AIS) patients with large vessel occlusion of the anterior circulation. Although the treatment effect is largely attributable to EVT, IVT may affect hypercoagulability during AIS.

Aims: To investigate the association between activated coagulation and final infarct volume and clinical outcomes (modified Rankin Scale 3-6 and mortality 90 days post-EVT), and whether this effect is modified by IVT administration.

Dynamic biomarker profiles in patients with paroxysmal atrial fibrillation: Assessing the differences between sinus rhythm and acute atrial fibrillation episode.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, yet its underlying pathophysiology remains poorly understood. This study assessed whether circulating biomarker concentrations differ in paroxysmal AF patients during an acute episode compared to sinus rhythm.

Methods: The Time of Calamity study is a prospective biomarker study within the RACE V study.

Mechanisms and management of thrombosis in cancer: focus on gastrointestinal malignancies.

Cancer patients have an increased risk of venous thromboembolism (VTE) which is their second cause of death after disease progression itself. Several thrombotic risk factors coexist in cancer patients, including the ability of both cancer and tumoral microenvironment's cells to directly or indirectly activate platelets and the enzymes of the coagulation cascade, resulting in a hyper-coagulable state of blood. This narrative review gives an overview of the main mechanisms leading to VTE in cancer patients, including the role that platelets and the clotting proteins may have in tumor growth and metastasis.

Current and potentially novel antithrombotic treatment in acute ischemic stroke.

Acute ischemic stroke (AIS) is the most common type of stroke and requires immediate reperfusion. Current acute reperfusion therapies comprise the administration of intravenous thrombolysis and/or endovascular thrombectomy. Although these acute reperfusion therapies are increasingly successful, optimized secondary antithrombotic treatment remains warranted, specifically to reduce the risk of major bleeding complications.

M6229 Protects against Extracellular-Histone-Induced Liver Injury, Kidney Dysfunction, and Mortality in a Rat Model of Acute Hyperinflammation.

Extracellular histones have been shown to act as DAMPs in a variety of inflammatory diseases. Moreover, they have the ability to induce cell death. In this study, we show that M6229, a low-anticoagulant fraction of unfractionated heparin (UFH), rescues rats that were challenged by continuous infusion of calf thymus histones at a rate of 25 mg histones/kg/h.

The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.

The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. We assessed prospectively different coagulation parameters in 71 patients with active AAV at baseline and after 6 months of follow-up. D-dimers and fibrinogen were increased in most patients at presentation and remained elevated in half of the patients.

Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort.

Background: Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality.

Platelet biology and function: plaque erosion vs. rupture.

The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes.

Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.

Introduction: Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19.

Methods: Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited.

Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis.

Introduction: Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown.

Methods: Monocytic tissue factor surface expression was investigated during three conditions.

Plasma Kallikrein as a Forgotten Clotting Factor.

For decades, it was considered that plasma kallikrein's (PKa) sole function within the coagulation cascade is the activation of factor (F)XII. Until recently, the two key known activators of FIX within the coagulation cascade were activated FXI(a) and the tissue factor-FVII(a) complex. Simultaneously, and using independent experimental approaches, three groups identified a new branch of the coagulation cascade, whereby PKa can directly activate FIX.

Predictive value for increased activated factor XI activity in acute venous thromboembolism.

Background: Venous thromboembolism (VTE) is associated with excessive coagulation activity, which in part can be attributed to activation of contact system. However, the knowledge regarding the impact of contact activation in acute VTE is limited.

Objective: To unravel the involvement of contact activation in acute VTE.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney.

Clinical utility of the 4S-AF scheme in predicting progression of atrial fibrillation: data from the RACE V study.

Aims: The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF.

Methods And Results: We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study.

Vascular Function, Systemic Inflammation, and Coagulation Activation 18 Months after COVID-19 Infection: An Observational Cohort Study.

Introduction: Among its effect on virtually all other organs, COVID-19 affects the cardiovascular system, potentially jeopardizing the cardiovascular health of millions. Previous research has shown no indication of macrovascular dysfunction as reflected by carotid artery reactivity, but has shown sustained microvascular dysfunction, systemic inflammation, and coagulation activation at 3 months after acute COVID-19. The long-term effects of COVID-19 on vascular function remain unknown.

Integrating Mechanisms in Thrombotic Peripheral Arterial Disease.

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, is underdiagnosed in the general population. Despite the extensive research performed to unravel its pathophysiology, inadequate knowledge exists, thus preventing the development of new treatments. This review aims to highlight the essential elements of atherosclerosis contributing to the pathophysiology of PAD.

Lower levels of vWF are associated with lower risk of cardiovascular disease.

Objective: The current study was undertaken to prospectively explore whether having low levels of von Willebrand factor (vWF) antigen and vWF activity reduce the risk for cardiovascular disease and death.

Methods: VWF antigen and vWF activity were measured by enzyme-linked immunosorbent assay and an immunological-based assay, respectively, in a subsample of 4857 individuals aged between 35 and 74 years old, enrolled between April 2007 and October 2008 in the population-based Gutenberg Health Study. VWF antigen and activity below the 20th percentile was set as a measure of "low vWF.

Serial thrombin generation and exploration of alternative anticoagulants in critically ill COVID-19 patients: Observations from Maastricht Intensive Care COVID Cohort.

Background: COVID-19 associated coagulopathy (CAC) is associated with an increase in thromboembolic events. Current guidelines recommend prophylactic heparins in the management of CAC. However, the efficacy of this strategy in the intensive care population remains uncertain.

Dual pathway inhibition as compared to acetylsalicylic acid monotherapy in relation to endothelial function in peripheral artery disease, a phase IV clinical trial.

Objective: Dual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.

Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism.

Introduction: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was to determine specific plasma signatures for proteins related to platelets in acute iPE and DVT-PE compared to isolated DVT (iDVT).

Methods: Within the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multicenter prospective cohort study of 693 confirmed VTE cases, a highly sensitive targeted proteomics approach based on dual-antibody proximity extension assay was applied.

Vitamin K antagonist use induces calcification and atherosclerotic plaque progression resulting in increased hypercoagulability.

Aims: Vascular calcification is a hallmark of atherosclerotic burden and can predict the cardiovascular outcome. Vitamin K antagonists (VKA) are widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis but are also associated with increase vascular calcification progression. We aim to unravel the paradox that VKA suppresses plasma coagulation but promotes vascular calcification and subsequent atherosclerosis-dependent coagulability of the vessel wall.

Prevalence and determinants of atrial fibrillation progression in paroxysmal atrial fibrillation.

Objective: Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.

Methods: In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed.

EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia.

Blood clot formation initiates ischemic events, but coagulation roles during postischemic tissue repair are poorly understood. The endothelial protein C receptor (EPCR) regulates coagulation, as well as immune and vascular signaling, by protease activated receptors (PARs). Here, we show that endothelial EPCR-PAR1 signaling supports reperfusion and neovascularization in hindlimb ischemia in mice.