Search results for "Coagulation"
showing 10 items of 381 documents
Self-assembled multivalent (SAMul) ligand systems with enhanced stability in the presence of human serum
2019
Self-assembled cationic micelles are an attractive platform for binding biologically-relevant polyanions such as heparin. This has potential applications in coagulation control, where a synthetic heparin rescue agent could be a useful replacement for protamine, which is in current clinical use. However, micelles can have low stability in human serum and unacceptable toxicity profiles. This paper reports the optimi- sation of self-assembled multivalent (SAMul) arrays of amphiphilic ligands to bind heparin in competitive conditions. Specifically, modification of the hydrophobic unit kinetically stabilises the self-assembled nanostructures, preventing loss of binding ability in the presence of…
Recombinant factor VIII: past, present and future of treatment of hemophilia A.
2018
The development of recombinant factor VIII (rFVIII) was initially driven by the necessity to treat hemophilia A (HA) patients with FVIII concentrates without the risk of transmitting infectious agents. Over the last three decades the safety of rFVIII has been further improved by completely removing animal or human proteins from the manufacturing process, so that patients would not be exposed to known or emerging pathogens. Recent efforts have concentrated on improving the expression of rFVIII, reducing its immunogenicity and enhancing its pharmacokinetic (PK) behavior. These new goals have been possible thanks to the develop-ment of biotechnology and a better knowledge of the function and s…
Analysis of cold activation of the contact system in hereditary angioedema with normal C1 inhibitor.
2021
Hereditary angioedema (HAE) attacks are caused by excessive activation of the contact system. Understanding how the contact system is activated in HAE, especially in patients with normal C1 inhibitor (HAEnCI), is essential to effectively treat this disease. Contact system activation involves the cleavage of several proteins including Factor XII (FXII), high molecular weight kininogen (HK), prekallikrein, sgp120 (ITIH4) and C1 inhibitor (C1-INH) before the subsequent generation of bradykinin that mediates HAE. In this study, we evaluated the fragmentation and enzymatic activity of contact system proteins in HAEnCI plasma samples before and after contact system activation induced by incubatio…
Proteases, Protease-Activated Receptors, and Atherosclerosis
2018
Coagulation activation by the TF (tissue factor) pathway plays pivotal roles in triggering platelets and precipitating acute coronary syndromes. Although dual antiplatelet therapy is effective in secondary cardiovascular prevention, combining platelet antagonism with low-dose aspirin and the oral coagulation FXa antagonist rivaroxaban has a synergistic clinical benefit over monotherapy in preventing the composite outcome of cardiovascular death, stroke, or myocardial infarction.1 It is, therefore, of considerable interest to understand the roles of coagulation proteases and their cell signaling effects in the development of atherosclerosis and vascular inflammation. Acute thrombosis in anim…
CD36-fibrin interaction propagates FXI-dependent thrombin generation of human platelets.
2019
Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with …
Comment on “Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemin…
2019
Although the interplay between tumor progression and blood coagulation has been recognized [...]
Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts
2021
Simple Summary Aberrant tissue factor (TF) expression by transformed myeloblasts and inflammatory monocytes contributes to coagulation activation in acute myeloid leukemia (AML). TF procoagulant activity (PCA) is regulated by protein disulfide isomerase (PDI), an oxidoreductase with chaperone activity, but its specific role in AML-associated TF biology is unclear. Here, we provide novel mechanistic insights into this interrelation. We show that bacitracin and rutin, two pan-inhibitors of the PDI family, prevent lipopolysaccharide (LPS)-induced monocyte TF production under inflammatory conditions and constitutive TF expression by THP1 cells and AML blasts, thus exerting promising anticoagula…
Cumulative visual impact of two coagulability disorders: A case report.
2020
Cumulative visual impact of two coagulability disorders were reviewed by presenting a case of a young female patient with a spontaneous abortion and two thromboembolic events in 8 years, whose visual function was severely affected. The particularities of her genetic constellation regarding the retinal circulation are also discussed. The patient developed a central retinal artery occlusion in the right eye during pregnancy in 2010, which led to an extended hematological workup that revealed presence of MTHFR C677T and MTHFR A1298C heterozygote mutations. The screening for myeloproliferative disorders showed JAK2 V617F gene mutation. Test results confirmed the diagnosis of thrombophilia and e…
Tissue factor at the crossroad of coagulation and cell signaling
2018
The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween it…
Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development
2017
Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)-dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expressi…