Serotonin secretion by blood platelets: accuracy of high-performance liquid chromatography-electrochemical technique compared with the isotopic test and use in a clinical laboratory.

Background: Mild secretion defects are the most frequent and challenging blood platelet disorders to diagnose. Most δ-granule secretion tests lack validation, are not quantitative, or have unreliable response to weak platelet agonists.

Objectives: To compare platelet serotonin secretion by HPLC-electrochemical detection technique (HPLC-ECD) with the reference isotopic test (H-5-HT), evaluating its performance in clinical laboratories.

Expert opinion on the use of platelet secretion assay for the diagnosis of inherited platelet function disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

Assessment of platelet secretion is crucial for diagnosing suspected inherited platelet function disorders (IPFD). A previous survey of the SSC on Platelet Physiology of the ISTH and a comprehensive review highlighted that most of the platelet secretion assays (PSAs) lack standardization and validation. The aim of this study was to provide expert consensus guidance on the use of PSAs for IPFD diagnosis.

Platelet activation by charged ligands and nanoparticles: platelet glycoprotein receptors as pattern recognition receptors.

Charge interactions play a critical role in the activation of the innate immune system by damage- and pathogen-associated molecular pattern receptors. The ability of these receptors to recognize a wide spectrum of ligands through a common mechanism is critical in host defense. In this article, we argue that platelet glycoprotein receptors that signal through conserved tyrosine-based motifs function as pattern recognition receptors (PRRs) for charged endogenous and exogenous ligands, including sulfated polysaccharides, charged proteins and nanoparticles.

Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions.

The role of glycoprotein VI (GPVI) in platelets was investigated in 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to the transmembrane domain, leading to expression of a truncated protein in the cytoplasm devoid of the transmembrane region. Western blotting and flow cytometry of GP6hom (homozygous) platelets confirmed loss of the full protein. The level of the Fc receptor γ-chain, which associates with GPVI in the membrane, was partially reduced, but expression of other receptors and signaling proteins was not altered.

Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3.

Increasing evidence suggests that platelets play a predominant role in colon and breast cancer metastasis, but the underlying molecular mechanisms remain elusive. Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin that triggers platelet activation through immunoreceptor tyrosine-based activation motif (ITAM) signaling and thereby regulates diverse functions, including platelet adhesion, aggregation, and procoagulant activity. GPVI has been proposed as a safe antithrombotic target, because its inhibition is protective in models of arterial thrombosis, with only minor effects on hemostasis.

Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report.

Healthy subjects frequently report minor bleedings that are frequently 'background noise' of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical.

Platelet glycoprotein VI genetic quantitative and qualitative defects.

Platelet membrane glycoprotein VI (GPVI) is increasingly recognized as an important receptor for thrombus formation and growth. Numerous arguments have been published indicating that GPVI plays a major role in thrombosis without being essential for physiological hemostasis. In humans, GPVI deficiencies are rarely reported.

Immobilized fibrinogen activates human platelets through glycoprotein VI.

Glycoprotein VI, a major platelet activation receptor for collagen and fibrin, is considered a particularly promising, safe antithrombotic target. In this study, we show that human glycoprotein VI signals upon platelet adhesion to fibrinogen. Full spreading of human platelets on fibrinogen was abolished in platelets from glycoprotein VI- deficient patients suggesting that fibrinogen activates platelets through glycoprotein VI.

Fibrin and D-dimer bind to monomeric GPVI.

Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, we show that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases.

Platelet tissue factor activity and membrane cholesterol are increased in hypercholesterolemia and normalized by rosuvastatin, but not by atorvastatin.

Background And Aims: High plasma LDL-cholesterol (LDL-C) and platelet responses have major pathogenic roles in atherothrombosis. Thus, statins and anti-platelet drugs constitute mainstays in cardiovascular prevention/treatment. However, the role of platelet tissue factor-dependent procoagulant activity (TF-PCA) has remained unexplored in hypercholesterolemia.

Inhibition of angiogenesis by platelets in systemic sclerosis patients.

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment.

Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome.

Background: Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied.

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption.

Background And Aims: Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption.

Methods And Results: Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases.

A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders.

Measurement of platelet granule release to detect inherited platelet secretion disorders (IPSDs) is essential for the evaluation of patients with abnormal bleeding and is necessary to distinguish which granule sub-types are affected and whether there is abnormal granule bio-synthesis or secretion. The radioactive serotonin incorporation and release assay, described before 1970, is still considered the "gold standard" test to assess platelet δ-granule release, although is unsuitable for clinical diagnostic laboratories. Luciferin-based assays, such as lumiaggregometry, are the most widely performed alternatives, although these methods do not distinguish defects in δ-granule biosynthesis from defects in secretion.

Changes in regional cerebral blood flow are associated with endothelial dysfunction markers in cocaine-dependent patients under recent abstinence.

Objectives: Cocaine is a known risk factor for several vascular ischemic events. The underlying mechanisms leading to the complications are not fully understood, although thrombus formation and accelerated atherosclerosis are prominent findings. Evidence of endothelial dysfunction (ED), a key phenomenon in the pathogenesis of atherogenesis, has been demonstrated in cocaine-dependent individuals.

Inhibition of platelet activation and thrombus formation by adenosine and inosine: studies on their relative contribution and molecular modeling.

Background: The inhibitory effect of adenosine on platelet aggregation is abrogated after the addition of adenosine-deaminase. Inosine is a naturally occurring nucleoside degraded from adenosine.

Objectives: The mechanisms of antiplatelet action of adenosine and inosine in vitro and in vivo, and their differential biological effects by molecular modeling were investigated.

Atorvastatin reduces the proadhesive and prothrombotic endothelial cell phenotype induced by cocaine and plasma from cocaine consumers in vitro.

Objective: Cocaine consumption is a risk factor for vascular ischemic complications. Although endothelial dysfunction and accelerated atherosclerosis have been observed in cocaine consumers, the mechanisms underlying their pathogenesis are not fully understood. This study aimed at identifying the effects of atorvastatin in relation to a proadhesive and prothrombotic phenotype induced by cocaine and plasma from chronic cocaine users on endothelial cells.

Is my patient a bleeder? A diagnostic framework for mild bleeding disorders.

Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery.

[New oral anticoagulant drugs].

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used.

Platelet activation in chronic cocaine users: effect of short term abstinence.

Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers.

Clot lysis time in platelet-rich plasma: method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid.

Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown.