Thrombosis research
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Thrombosis research · Nov 2019
First visualization of circulating neutrophil extracellular traps using cell fluorescence during human septic shock-induced disseminated intravascular coagulation.
Disseminated intravascular coagulation (DIC) is a severe complication of septic shock. Polymorphonuclear neutrophils (PMNs) may play a key role in septic shock-induced DIC via the release of neutrophils extracellular traps (NETs). NETs capture invading pathogens, but also act as a pro-coagulant surface at the interface between immunity and thrombosis. ⋯ Fluorescence images of NETs were associated to extracellular cytoplasmic expansions. Our data report for the first time the direct visualization of circulating NETs in patients with septic shock-induced DIC. The in vivo relevance of previously reported indirect markers of NETosis (neutrophil side fluorescence) is confirmed.
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Thrombosis research · Oct 2019
Healthcare resource utilization and costs among patients with direct oral anticoagulant or warfarin-related major bleeding.
Direct oral anticoagulants (DOACs) have expanded the options for antithrombotic therapy. DOAC-related major bleeds are associated with favorable outcomes compared to warfarin in clinical trials and routine practice. However, it is unclear whether management of DOAC-associated major bleeding incurs higher resource utilization and costs. ⋯ Prior to introduction of DOAC-specific reversal agents, resource utilization and medical costs were comparable between DOAC- and warfarin-associated major bleeds, despite marginally higher blood product costs incurred by the former. Resource intensity associated with anticoagulant-related bleeding remains high, and our data provide measures for cost-effectiveness evaluation of emerging DOAC antidotes.
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Thrombosis research · Oct 2019
Genetic and clinical characterization of congenital fibrinogen disorders in Polish patients: Identification of three novel fibrinogen gamma chain mutations.
Congenital fibrinogen disorders are poorly explored in Slavic populations. The aim of this study was to characterize the genetic background and clinical manifestations of fibrinogen disorders in the Polish case series. ⋯ This study of the largest cohort of Slavic patients with congenital fibrinogen disorders has enabled the identification of 3 new FGG mutations and shows a high prevalence of bleeding manifestations with recurrences.
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Thrombosis research · Oct 2019
DTI/DXI interferences with global coagulation tests in emergency hospital admissions - Results of the prospective Dresden NOAC Registry (NCT01588119).
Depending on test assays and the time of last DOAC intake, direct thrombin inhibitors (DTI) and direct FXa inhibitors (DXI) may or may not affect prothrombin time (PT), international normalized ratio (INR) or activated thromboplastin time (aPTT) but the clinical impact is unknown. ⋯ Many DOAC recipients present with elevated PT, INR or aPTT during emergency admissions but false negative values within 12 h of last intake as well as elevated values beyond 24 h after last DOAC intake are common. Both scenarios may result in clinical misinterpretation and, potentially, in patient harm, also because DOAC specific testing is rarely performed in emergency settings.
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Thrombosis research · Aug 2019
Neutrophil extracellular traps induced by activated platelets contribute to procoagulant activity in patients with colorectal cancer.
Patients with colorectal cancer (CRC) are at increased risk of venous thrombosis, but the precise mechanisms of thrombogenesis in CRC remain largely unknown. We aimed to identify the novel role of neutrophil extracellular traps (NETs) in the induction of procoagulant activity (PCA) in CRC, and to evaluate its interactions with platelets and endothelial cells (ECs). In this study, we first showed that the levels of NETs in the peripheral blood of CRC patients were increased in parallel with cancer progression and reached significance in stage II patients compared to healthy subjects. ⋯ The PCA of NETs-activated platelets or ECs could be inhibited either by the cleavage of NETs with DNase1 or the blockage of histone with activated protein C (APC). Our results reveal the complex interactions between neutrophils, platelets and ECs and their potential role in the hypercoagulable state in CRC. We propose that NETs may provide new therapeutic targets to combat the thrombotic consequences of CRC.