Microvesicules

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet αIIb β3 integrin. Platelet transfusions can be followed by an immune response that can block integrin function by interfering with fibrinogen binding. OBJECTIVES: In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. METHODS: Twelve patients with GT were evaluated for anti-αIIb β3 isoantibodies...

Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, we test the hypothesis that sheared PDMPs manifest phenotypical heterogeneity of morphology and receptor surface expression and modulate platelet hemostatic function...

OBJECTIVE: Implantable cardiovascular therapeutic devices (CTD) including stents, percutaneous heart valves and ventricular assist devices, while lifesaving, impart supraphysiologic shear stress to platelets resulting in thrombotic and bleeding device-related coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of platelet-derived microparticles (PDMPs)...

Southeast Asian ovalocytosis (SAO) is characterized by the misfolding of band 3 protein in red blood cells (RBC). The abnormal structure of the band 3 protein results in dysmorphic RBC and related functions. Previous data showed that in vitro storage under hypothermic conditions alters band 3 protein structure and function. Microvesiculation includes shedding of RBC membranes, called RBC-derived microparticles/extracellular vesicles (RMP/EVs), and storage lesions. Unfortunately, there is no evidence of RBC microvesiculation under in vitro storage conditions in heterozygous SAO individuals...

Introduction: Patients with glioma (GM) are at a high risk of venous thromboembolism (VTE). The role of microvesiculation in the cancer-associated thrombosis mechanisms has been previously demonstrated. This study aimed to evaluate the relative abundance of extracellular vesicles (EVs) and thrombin generation (TG) in combination with standard laboratory tests in patients with newly diagnosed GM as potential prognostic markers in VTE. Materials and Methods: In the present study, 11 patients with newly diagnosed GM and 10 healthy volunteers were analyzed...

Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner...

Prestorage filtration of blood to remove contaminating donor leukocytes and platelets has substantially increased the safety level of transfusion therapy. We have previously shown that leukoreduction has a mitigating effect on the storage lesion profile by lowering the extent of hemolysis and of RBC aging and removal phenotypes, including surface signaling and microvesiculation. Even though protein composition may determine the fate of EVs in the recipient, the probable effect of leukoreduction on the EV proteome has been scarcely investigated...

Structurally, aquaporins (AQPs) are small channel proteins with monomers of ~ 30 kDa that are assembled as tetramers to form pores on cell membranes. Aquaporins mediate the conduction of water but at times also small solutes including glycerol across cell membranes and along osmotic gradients. Thirteen isoforms of AQPs have been reported in mammalian cells, and several of these are likely expressed in platelets. Osmotic swelling mediated by AQP1 sustains the calcium entry required for platelet phosphatidylserine exposure and microvesiculation, through calcium permeable stretch-activated or mechanosensitive cation channels...

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy...

Most agonists stimulate platelet Ca2+ rises via G-protein coupled receptors (GPCRs) or ITAM-linked receptors (ILRs). Well studied are the GPCRs stimulated by the soluble agonists thrombin (PAR1, PAR4), ADP (P2Y1 , P2Y12 ), and thromboxane A2 (TP), signaling via phospholipase (PLC)β isoforms. The platelet ILRs glycoprotein VI (GPVI), C-type lectin-like receptor 2 (CLEC2), and FcγRIIa are stimulated by adhesive ligands or antibody complexes and signal via tyrosine protein kinases and PLCγ isoforms. Marked differences exist between the GPCR- and ILR-induced Ca2+ signaling in: (i) dependency of tyrosine phosphorylation; (ii) oscillatory versus continued Ca2+ rises by mobilization from the endoplasmic reticulum; and (iii) smaller or larger role of extracellular Ca2+ entry via STIM1/ORAI1...

BACKGROUND: Thrombospondin-1 (TSP-1), a Ca2+ -binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+ dynamics, survival, and deformability of human red blood cells (RBCs)...

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy...

Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage. Parkin represents an autosomal recessive inherited gene for Parkinson's disease and an important member of selective autophagy for mitochondria. The association between Parkinson's disease and alcoholic injury remains elusive. This study aimed to examine the effect of parkin deficiency on chronic alcohol intake-induced organ injury in brain, liver and skeletal muscle (rectus femoris muscle)...

Recent studies indicate that erythrocytes actively modulate blood clotting and thrombus formation. The lipid mediator lysophosphatidic acid (LPA) is produced by activated platelets, and triggers a signaling process in erythrocytes. This results in cellular calcium uptake and exposure of phosphatidylserine (PS) at the cell surface, thereby generating activated membrane binding sites for factors of the clotting cascade. Moreover, erythrocytes of patients with a bleeding disorder and mutations in the scramblase TMEM16F show impaired PS exposure and microvesiculation upon treatment with calcium ionophore...

BACKGROUND: Recognition of rickettsialpox infection on skin biopsy can be challenging. The histopathology is nonspecific and inconsistently described. We assess classic histopathologic features in confirmed cases and review the literature. METHODS: We searched for cases of "rickettsialpox" diagnosed between 2006-2018 with positive immunostaining for Spotted Fever Group Rickettsia species. Original slides were evaluated for vacuolar alterations, granulomatous inflammation, vasculitis, necrosis, fibrin thrombi, microvesiculation, papillary dermal edema and extravasated red blood cells...

Physiologically, upon platelet activation, uncontrolled propagation of thrombosis is prevented by regulating mechanisms which affect the expression and function of either platelet adhesion receptors or integrins. Receptor ectodomain shedding is an elective mechanism which is mainly involved in down-regulation of adhesion receptors GPIbα and GPVI. Platelet integrin αIIb β3 can also be modulated with a calpain-dependent proteolytic cleavage. In addition, activating signals may induce the internalization of expressed receptors to selectively down-regulate their intensity...

Transfusion of red cell concentrates is an essential lifesaving treatment for patients with massive bleeding or red blood cell disorders. However, correlations between blood transfusion from female donors, especially in sex mismatched transfusions, and a risk of mortality has been reported. A systematic understanding of how sex-mismatched transfusion can contribute to negative outcomes is still lacking. Here, we propose that variations in stored red blood cell products from female and male blood donors may be related to different characteristics of subpopulations of RBCs in units...

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant...

OBJECTIVE: To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. DESIGN: Experimental interventional study. SETTING: University. ANIMALS: Twenty-four healthy ex-racing Greyhounds. INTERVENTIONS: Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0...

Collagen is a major component of the subendothelial matrix and participates in bleeding arrest by activating and aggregating platelets at the site of vascular injury. The most common type I collagen exists in both soluble and fibrillar forms, but structural exchangeability between the two forms is currently unknown. Using atomic force microscopy, we show that type I collagen switches between soluble and fibrillar forms in a pH-dependent and ion-independent manner. Fibrillar collagen is rope like with characteristic "D-bands...