: High patient age is a strong predictor of poor outcome in trauma patients. The present study investigated the effect of age on mortality and biomarkers of sympathoadrenal activation, tissue, endothelial, and glycocalyx damage, coagulation activation/inhibition, fibrinolysis, and inflammation in trauma patients at admission. : Prospective observational study. : Single ...

Substantial activation of platelets can occur in the course of hemodialysis. Platelet surface markers show evidence of platelet degranulation. Some activation occurs due to exposure of blood to the roller pump segment and microbubbles may play a role. Platelet activation seems to be reduced with reused dialyzers or with those ...

The extracellular matrix is continually remodelled by the action of various enzymes such as heparanase, which specifically targets heparan sulfate (HS) and is found in human platelets at high levels. The activity of heparin-containing hydrogels following incubation with platelet extract (PE) was investigated in order to simulate the responses that ...

BACKGROUND: Lipids and other biologically active substances accumulate in platelet concentrates (PCs) during storage. Some of these substances have been suggested to modulate immune responses and to play a pathogenic role in the development of transfusion-related acute lung injury. This study compared the content and impact of some biological response ...

Bivalirudin (BV), a peptidic direct thrombin inhibitor, derived from hirudin, has gained increasing interest in clinical anticoagulant therapy in the recent years. In this work, a hemocompatible surface was prepared by immobilization of BV on 316L stainless steel (SS) using a bonding layer of polydopamine (DA). X-ray photoelectron spectroscopy (XPS) ...

Platelet aggregation, secretion and thrombus formation play a critical role in primary hemostasis to prevent excessive blood loss. On the other hand, uncontrolled platelet activation leads to pathological thrombus formation resulting in myocardial infarction or stroke. Stimulation of heterotrimeric G-proteins by soluble agonists or immunoreceptor tyrosine based activation motif-coupled receptors ...

AMG X, a human neutralizing monoclonal antibody (mAb) against a soluble human protein, caused thrombocytopenia, platelet activation, reduced mean arterial pressure, and transient loss of consciousness in cynomolgus monkeys after first intravenous administration. In vitro, AMG X induced activation in platelets from macaque species but not from humans or baboons. ...

The triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-like transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. In ...

INTRODUCTION: Curdione, one of the major sesquiterpene compounds from Rhizoma Curcumae, has been shown to exhibit multiple bioactive properties. In this study, we investigated the anti-platelet aggregation and antithrombotic activities of curdione with different methods both in vitro and in vivo. The purpose of the study was to explore an ...

Objective-To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay. Animals-6 healthy adult mixed-breed dogs. Procedures-Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, ...

Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition. In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF), of which 30 with dengue shock syndrome (DSS), we measured ...

Limited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor ...

OBJECTIVE: Staphylococcus aureus can induce platelet aggregation. The rapidity and degree of this correlates with the severity of disseminated intravascular coagulation, and depends on platelet peptidoglycans. Surface-located thiol isomerases play an important role in platelet activation. The staphylococcal extracellular adherence protein (Eap) functions as an adhesin for host plasma proteins. ...

Surface ion equilibrium is hypothesized to play an important role in defining the interactions between foreign materials and biological systems. In this study, we compare two surfaces with respect to their ability to activate adhering platelets. One is a commonly used implant material TiO(2), which binds Ca(2+), and the other ...

INTRODUCTION: Sclerotherapy is associated with thromboembolic and ischemic neurological adverse events but the effects of sclerosants on platelet function are unknown. The aim of this study was to investigate the in vitro effects of detergent sclerosants Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on platelet activation and aggregation. MATERIALS AND ...

OBJECTIVE: Although failure to achieve an adequate activated coagulation time (ACT) after full heparinization before cardiopulmonary bypass often is attributed to antithrombin (AT) deficiency, it remains unclear if this is a causative mechanism of decreased heparin responsiveness. Therefore, the authors determined the relationship between AT and other coagulation-related factors that ...

Inorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic and proinflammatory effects in vivo. Long-chain polyphosphate-of the size present in infectious microorganisms-is a potent, natural pathophysiologic activator of the contact pathway of blood clotting. Medium-chain polyphosphate-of the size secreted from activated human platelets-accelerates factor V activation, completely abrogates ...

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. The phytochemical investigation of stilbenoids from Gnetum macrostachyum Hook. f. led to the isolation of trans-resveratrol (1), isorhapotigenin (2), gnetol (3), bisisorhapontigenin B ...

Because novel direct acting anticoagulants are being tested in the secondary prevention of cardiovascular events, we assessed potential effects of a direct acting antagonist of Factor Xa on platelet function. Blood from patients with known coronary artery disease who were treated with aspirin but no other antithrombotic agent was spiked ...

AIM: Abdominal aortic aneurysm (AAA) is associated with chronic mural inflammation and a pro-thrombotic diathesis. It has been suggested that both may be related to biologically active intra-sac thrombus. The aim of this study was to examine the relationship between thrombin generation, fibrinolysis, platelet activity and AAA sac thrombus volume. ...

In efforts to define new targets for antithrombotic purposes, there is interest in utilizing antibodies targeting ligand binding domains of platelet receptors. To this end, we have recently shown that an antibody (designated C-EL2Ab), which targets the C-terminus of the 2nd extracellular loop (C-EL2) of the thromboxane A(2) receptor (TPR), ...

Inorganic polyphosphate (polyP) is abundant in biological organisms. PolyP is a major component of dense granules of human platelets and is secreted upon platelet activation. Studies from our lab and others have shown that polyP is a potent modulator of the blood clotting cascade, acting as a pro-hemostatic, prothrombotic and ...

Thrombin generates fibrin and activates platelets and endothelium, causing thrombosis and inflammation. Endothelial thrombomodulin (TM) changes thrombin's substrate specificity towards cleavage of plasma protein C into activated protein C (APC), which opposes its thrombotic and inflammatory activities. Endogenous TM activity is suppressed in pathological conditions and anti-thrombotic interventions involving soluble ...

Platelet-mimetic synthetic hemostats are highly attractive in transfusion medicine. To this end, past research reports have described particles that either amplify platelet aggregation or mimic platelet adhesion. However, a construct design that effectively combines both functionalities has not been reported. Here, we describe the design of a liposomal construct simultaneously ...

Background and purpose:  Ginsenosides are the main constituents for the pharmacological effects of Panax ginseng. Such effects of ginsenosides including cadioprotective and anti-platelet activities have shown stability and bioavailability limitations. On the other hand, information on antiplatelet activity of Ginsenosides-Rp1 (G-Rp1), a stable derivative of ginsenoside-Rg3, is scarce. We examined ...

OBJECTIVES:: Intravasation of bone marrow contents into venous circulation and pulmonary embolization after intramedullary nailing may be coupled with the activation of coagulation and fibrinolytic cascades. The objective of this study was to assess hemostatic response to pulmonary extravasated marrow contents. We hypothesize that activation of platelet activity and the ...

OBJECTIVE: Argan oil has been shown to inhibit in vitro and ex vivo platelet aggregation without extending bleeding time. In this report, we examined in vivo the antithrombotic activity of argan oil in an experimental thrombosis model in mice: acute pulmonary thromboembolism and in vitro its effect in a coagulation assay. METHODS: Acute pulmonary ...

Patients with heparin-induced thrombocytopenia (HIT) remain at risk for recurrent thromboembolic complications despite improvements in management. HIT is caused by antibodies that preferentially recognize ultralarge complexes (ULC) of heparin and platelet factor 4 (PF4) tetramers. We previously demonstrated that a variant PF4(K50E) forms dimers but does not tetramerize or form ...

Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactoside-binding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance ...

Recombinant activated coagulation factor VII (rFVIIa) has proven to be a useful prohemostatic agent in patients with hemophilia and antibody inhibitors. It has also been used off-label in other settings. A major mechanism of its hemostatic efficacy is its ability to activate factor X on the surface of activated platelets ...

Interactions of Staphylococcus aureus ( S. aureus ) and platelets play an important role in the pathogenesis of intravascular infections such as infective endocarditis (IE). A typical feature of S. aureus is the ability to generate thrombin activity through the secretion of two prothrombin activating molecules, staphylocoagulase and von Willebrand ...

Severe bacterial sepsis often leads to a systemic procoagulant and proinflammatory condition that can manifest as disseminated intravascular coagulation (DIC), septic shock, and multiple organ failure. Since activation of the contact proteases factor XII (FXII), prekallikrein, and factor XI (FXI) can trigger coagulation and inflammatory responses, the contact factors have ...

Cisplatin (cis-diamminedichloroplatinum II) is one of the most widely used anti-tumor agents. However, cisplatin-based chemotherapy is usually accompanied by adverse side effects such as thrombocytopenia, and the mechanism remains unclear. Here we show that cisplatin induced several platelet apoptotic events including up-regulation of Bax and Bak, down-regulation of Bcl-2 and ...

A series of novel benzocoumarin amide derivatives have been synthesized and evaluated for their anti-thrombotic activity. Amongst these, compounds 5, 7 and 8 exhibited promising anti-thrombotic profile in an established model of mouse thrombosis. Hence, comprehensive profiling on platelet aggregation and coagulation parameters was carried out to assess its potential ...

Background and purpose: Developing novel anti-platelet strategies is fundamental to reducing the impact of thrombotic diseases. Thrombin activates platelets via protease-activated receptors (PARs), and PAR antagonists are being evaluated in clinical trials for prevention of arterial thrombosis. However, one such trial was recently suspended due to increased bleeding in patients ...

The methanol extract of the twigs of Garcinia hombroniana, which showed strong LDL antioxidation and antiplatelet aggregation activities, was subjected to column chromatography to obtain 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone, 1,7-dihydroxyxanthone and eight triterpenoids, garcihombronane B, D, E and F, friedelin, glutin-5-en-3β-ol, stigmasterol and lupeol. The structures of the compounds were elucidated by spectroscopic ...

INTRODUCTION: Flow cytometry allows the analysis of multiple antigens in a single tube at a single cell level. We present a rapid and sensitive two tube flow cytometric protocol for the detection of multiple platelet antigens and activation markers gated on a pure platelet population. MATERIALS AND METHODS: The presence ...

In a paper recently published in haematologica in 2011, van Bladel et al. found that the state of activation of platelets is up-regulated in patients with severe hemophilia A, as compared to patients with mild/moderate hemophilia A and to healthy donors. An earlier report had however failed to find signs ...

A high-throughput screen of the NIH-MLSMR compound collection, along with a series of secondary assays to identify potential targets of hit compounds, previously identified a 1,3-diaminobenzene scaffold that targets protease-activated receptor 1 (PAR1). We now report additional structure-activity relationship (SAR) studies that delineate the requirements for activity at PAR1 and ...

Background: Despite growing popularity of herbal medicines and natural food supplements, their effects on cardiovascular homeostasis remain largely unknown, especially regarding pro-thrombotic risks. Objective: Here, 21 herbal tea extracts were screened for the procoagulant activities on platelets, an important promoter of thrombosis to examine if herbal medicines or natural products may have ...

Background: The conversion of prothrombin to thrombin is one of two non-duplicated enzymatic reactions during coagulation. Thrombin has long been considered an optimal anticoagulant target because it plays a crucial role in fibrin clot formation by catalyzing the cleavage of fibrinogen, upstream coagulation cofactors, and platelet receptors. Although a number of ...

OBJECTIVE:The determinants of subarachnoid hemorrhage (SAH) volume and an atypical pattern of blood are not clear. Our objective was to determine if reduced platelet activity on admission and abnormal venous drainage are associated with greater SAH volume. METHODS:We prospectively identified noncomatose patients with SAH without an identifiable aneurysm. We routinely ...

Protein S (ProS) is an essential plasma protein that enhances the anticoagulant activity of activated protein C (APC). In vitro, purified native human Zn2+-containing ProS also exerts direct anticoagulant activity by inhibiting prothrombinase and extrinsic FXase activities independently of APC. We investigated antithrombotic effects of ProS infused without APC in ...

Platelets participate in the development and progression of atherosclerosis. During this process they interact with endothelial cells and leukocytes. Therefore, we investigated the associations between carotid atherosclerosis and platelet reactivity markers. The platelet surface expression of P-selectin (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding of PAC-1), as ...

Activated platelets form transient aggregates with monocytes in circulation and have a half-life of approximately 30-60min. These complexes are increased in various inflammatory conditions and are an early marker of myocardial infarction. HIV-1 infection is associated with chronic inflammation, and increased CD16(+) inflammatory monocytes have been observed in these individuals, ...

The Ca(2+)-activated proteases or calpains, play a crucial role in a specific spectrum of physiological processes such as cytoskeletal remodeling, cellular signaling, cell migration, apoptosis, cell survival and platelet activation, by the proteolytic cleavage of target proteins. Rather than eliciting protein degradation the calpains are responsible for their modification (e.g. ...

Platelets and their activation have a pivotal role in the development of atherosclerotic diseases such as acute myocardial infarction (AMI), stroke and peripheral arterial occlusion. Biomarkers of platelet activation are making inroads into clinical studies and may serve as promising agents upstream to established downstream markers of myocardial necrosis such ...

Platelets are known to play a fundamental role in acute coronary syndromes. After atherosclerotic plaque rupture, platelets can form pathogenic, occlusive thrombi leading to acute ischemic events. Today there are promising results from recently developed antiplatelet agents. However, morbidity and mortality from acute coronary syndromes remain significant despite the administration ...

The goal of this study was to evaluate annexin V-positive microparticles (MPs) and neutrophil activation in humans following decompression from open-water SCUBA diving with the hypothesis that changes are related to intravascular bubble formation. Sixteen male volunteer divers followed a uniform profile of four daily SCUBA dives to 18 meters ...

Short activated partial thromboplastin times (APTTs) are associated with thrombosis. However, what short APTTs actually represent in terms of possible mechanistic pathways is not well characterized. We have assessed thrombin generation as compared with levels of procoagulant factor (fibrinogen, V, VIII, IX, XI and XII) activities, von Willebrand factor level ...