scholarly journals On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation

2016 ◽  
Vol 40 (10) ◽  
pp. 971-980 ◽  
Author(s):  
Filippo Consolo ◽  
Lorenzo Valerio ◽  
Stefano Brizzola ◽  
Paolo Rota ◽  
Giulia Marazzato ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Extracorporeal Circulation ◽  
Platelet Activity ◽  
Activity State

Platelet Activation and Free Emboli Formation in Flow Past Mechanical Heart Valves

2002 ◽  
Author(s):  
Danny Bluestein ◽  
Wei Yin ◽  
Jolyon Jesty ◽  
Adam E. Saltman ◽  
Irvin B. Krukenkamp ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Left Ventricular ◽  
Mechanical Heart Valves ◽  
Shear Stresses ◽  
Platelet Activity ◽  
Flow Past ◽  
Activity State ◽  
Valve Implantation

Numerical studies, in vitro, and in vivo measurements were conducted, aimed at quantifying free emboli formation and procoagulant properties of platelets induced by flow past mechanical heart valves (MHV). Pulsatile turbulent flow simulation was conducted past a St. Jude medical MHV in the aortic position, to study the effects of valve implantation technique on the thromboembolic potential of the valve. A misaligned valve with subannualarly sutured pledgets produced accelerating jet flow through the valve orifices and a wider wake of shed vortices. Shear stress histories of platelets along turbulent trajectories exposed the platelets to elevated shear stresses around the leaflets, leading them to entrapment within the shed vortices. In vitro platelet studies were conducted past the MHV mounted in a recirculation flow loop and in a model of left ventricular assist device (LVAD), using an innovative platelet activity state (PAS) assay. The platelet activation significantly increased as a function of the recirculation time past the valve, and as compared to controls. Transcranial Doppler (TCD) measurements were conducted in the carotid artery of sheep with implanted MHV, showing marked increase in the number of HITS (High Intensity Transient Signals) signifying the passage of free emboli generated by the valve. The HITS were analyzed to distinguish between gaseous and thrombi emboli. Finally, platelet activity state measurements were conducted with sheep platelets, showing marked increase of platelet activation after valve implantation.

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis

2019 ◽  
Vol 39 (04) ◽  
pp. 392-397
Author(s):  
Wei Wang ◽  
Songqing Lai ◽  
ZiJin Xiao ◽  
Haiyue Yan ◽  
Yongxi Li ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiplatelet Agent ◽  
Wnt Signalling ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Platelet Activity ◽  
Occlusion Time ◽  
Negative Effect

AbstractPlatelets play a crucial role in haemostasis and several pathophysiological processes. Collagen is a main initiator for platelet activation and aggregation. Given that Wnt signalling negatively regulates platelet function, and IWR-1 (a small molecule inhibitor for Wnt signalling) has the potential of inhibiting collagen synthesis, it is essential to investigate whether IWR-1 regulates collagen-induced platelet activation and protects against thrombogenesis. In the present study we found that IWR-1 pretreatment effectively suppressed collagen-induced platelet aggregation in a dose-dependent manner. In addition, IWR-1 also resulted in a decrease of P-selectin and phosphatidylserine surface exposure using fluorescence-activated cell sorting analysis. In vitro studies further revealed that IWR-1 had a negative effect on integrin a2β1 activation and platelet spreading. More importantly, the results from in vivo studies showed that IWR-1 exhibited a robust bleeding diathesis in the tail-bleeding assay and a prolonged occlusion time in the FeCl3-induced carotid injury model. Taken together, current results demonstrate that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new antiplatelet agent.

Anthocyanins from red cabbage extract — evidence of protective effects on blood platelets

2012 ◽  
Vol 7 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Joanna Saluk ◽  
Michał Bijak ◽  
Joanna Kołodziejczyk-Czepas ◽  
Małgorzata Posmyk ◽  
Krystyna Janas ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Protective Effects ◽  
Platelet Activity ◽  
Red Cabbage ◽  
Arachidonate Cascade ◽  
Wide Range ◽  
Antioxidative Effects

AbstractRed cabbage belongs to cruciferous vegetables recognized as a rich source of anthocyanins. Anthocyanins have a wide range of therapeutic advantages without adverse effects, including cardiovascular protective properties. For development of cardiovascular diseases, platelet activation is crucial; therefore compounds which inhibit platelet activation are sought after. The anti-platelet activity of anthocyanins has only been described and is still unclear. In our study, the extract of anthocyanins, obtained from fresh leaves of red cabbage, was used in vitro to examine their antioxidative effects on platelets under oxidative stress conditions which are responsible for hyperactivity of these cells. The antiplatelet and antioxidative activities were determined by platelet aggregation and specific markers of the arachidonate cascade with O2−· generation, and oxidative changes (carbonyl groups and 3-nitrotyrosine). Extracts (5–15 μM) protected platelet proteins and lipids against oxidative damage, and diminished platelet activation. Anthocyanins from red cabbage provided beneficial anti-platelet effects and might help prevent cardiovascular diseases.

Effects of Valve Design and Orientation on Flow Induced Platelet Activation in Mechanical Heart Valves

2004 ◽  
Author(s):  
Wei Yin ◽  
Yared Alemu ◽  
Jolyon Jesty ◽  
Danny Bluestein
Keyword(s):  
Shear Stress ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
Cumulative Effect ◽  
Left Ventricular ◽  
Platelet Activity ◽  
Ventricular Assist ◽  
Activity State ◽  
Blood Flow Patterns

A study was conducted to estimate the thromboembolic potential of different Mechanical Heart Valve (MHV) designs and the effect of valve orientation (valve axial misalignment during implantation) on it. CFD simulations of turbulent, transient, non-Newtonian blood flow patterns generated by two types of MHVs (monoleaflet and bileaflet) and the effect of valve orientation were conducted using the Wilcox k-ω turbulence model. Platelet shear stress histories (cumulative effect of shear stress and time) were calculated and averaged over a large number of platelet trajectories within the flow field, and compared with in vitro Platelet Activity State (PAS) measurements conducted in a left ventricular assist device (LVAD) model. Platelets were circulated in the LVAD with Carbomedics bileaflet and Bjork-Shiley monoleaflet MHVs correspondingly. The PAS measurement indicated that PAS induced by the tilted St. Jude bileaflet MHV and the untilted valve was very similar (P>0.1). The bileaflet MHV activated platelets at a rate of more than 2-fold than that observed with the monoleaflet MHV (P<0.05). This confirmed the CFD platelet shear stress histories, which clearly indicated a higher level of stimulation of platelets for the bileaflet MHV.

scholarly journals Preparations from Selected Cucurbit Vegetables as Antiplatelet Agents – An in Vitro Study

2021 ◽  
Author(s):  
Agata Rolnik ◽  
Bartosz Skalski ◽  
Anna Stochmal ◽  
Beata Olas
Keyword(s):  
Platelet Activation ◽  
Cucurbita Pepo ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
In Vitro Study ◽  
Blood Platelet ◽  
Arachidonic Acid Metabolism ◽  
Platelet Activity ◽  
Activated Platelets

Abstract Increased blood platelet activation plays an important role in cardiovascular diseases (CVDs). Recent experiments indicate that certain fruits and vegetables, including onion, garlic, and beetroot, have anti-platelet potential and therefore may reduce the likelihood of CVDs. While vegetables from the Cucuritaceae family are known to exerting beneficial antioxidant and anti-inflammatory effects, their effects on blood platelet activation are poorly understood. Therefore, the aim of the present study was to determine the effect on platelet adhesion of preparations from selected cucurbits: pumpkin (Cucirbita pepo; fruit without seeds), zucchini (Cucurbita pepo convar. giromontina; fruit with seeds), cucumber (Cucumis sativus; fruit with seeds), white pattypan squash (Cucurbita pepo var. patisoniana; fruit without seeds) and yellow pattypan squash (Cucurbita pepo var. patisoniana, fruit without seeds). It also evaluates the activity of these preparations on enzymatic lipid peroxidation in thrombin-activated washed blood platelets by TBARS assay. The study also determines the anti-platelet and anticoagulant properties of these five cucurbit preparations in whole blood by flow cytometry and with the total thrombus-formation analysis system (T-TAS) and evaluates the cytotoxicity of the tested preparations against platelets based on LDH activity. The results indicate that the yellow Cucurbita pepo var. patisoniana preparation demonstrated stronger anti-platelet properties than the other tested preparations, reducing the adhesion of thrombin-activated platelets to collagen/fibrinogen, and inhibiting arachidonic acid metabolism and GPIIb/IIIa expression on 10 µM ADP-activated platelets. None of the preparations was found to cause platelet lysis. Our findings provide new information on the anti-platelet activity of the tested cucurbit preparations and their potential for treating CVDs associated with platelet hyperactivity.

Platelet Activation in Flow Past Mechanical Heart Valves

2001 ◽  
Author(s):  
Danny Bluestein ◽  
Jolyon Jesty ◽  
Adam E. Saltman ◽  
Irvin B. Krukenkamp ◽  
Krishnamurthy Suresh
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Mechanical Heart Valves ◽  
Implantation Technique ◽  
Shear Stresses ◽  
Flow Past ◽  
Activity State ◽  
Valve Implantation

Abstract Numerical studies, in vitro, and in vivo measurements were conducted, aimed at quantifying free emboli formation and procoagulant properties of platelets induced by flow past mechanical heart valves (MHV). Pulsatile turbulent flow simulation was conducted past a St. Jude medical MHV in the aortic position, to study the effects of valve implantation technique on the thromboembolic potential of the valve. A misaligned valve with subannualarly sutured pledgets produced accelerating jet flow through the valve orifices and a wider wake of shed vortices. Shear stress histories of platelets along turbulent trajectories exposed the platelets to elevated shear stresses around the leaflets, leading them to entrapment within the shed vortices. In vitro platelet studies were conducted past the MHV mounted in a recirculation flow loop, by measuring the platelets ability to support the activation of acetylated human prothrombin by factor xa, which enables sequestering flow induced effects and quantification of the platelets activity state. The platelet activation state increased monotonically as a function of the recirculation time past the valve, as measured by the thrombin generation rates in the assay. Finally, platelet activity state measurements were conducted in vivo, from a sheep with an implanted MHV, showing marked increase of platelet activation after valve implantation.

scholarly journals The binding of autotaxin to integrins mediates hyperhomocysteinemia-potentiated platelet activation and thrombosis

2021 ◽  
Author(s):  
Lulu Han ◽  
Yutong Miao ◽  
Yang Zhao ◽  
Xingzhong Zhang ◽  
Xiaolong Ma ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Vascular Injury ◽  
Thrombus Formation ◽  
Membrane Phospholipid ◽  
Platelet Activity ◽  
Clot Retraction ◽  
Integrin Αiibβ3 ◽  
Phospholipid Hydrolysis ◽  
Primary Hemostasis

Hyperhomocysteinemia (HHcy) is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Here, a human medical examination report showed that elevated human plasma Hcy levels were positively correlated with enhanced blood coagulation and platelet activity, suggesting that humans with HHcy are more prone to thrombus formation at the sites of vascular injury. Accordingly, we observed accelerated platelet activation, primary hemostasis, and thrombus formation both in acute and chronic HHcy ApoE-/- mice. Upon Hcy administration in C57BL/6J mice, platelet aggregation, spreading, and clot retraction were markedly promoted. More importantly, homocysteine (Hcy) increased the affinity of platelet integrin αIIbβ3 with ligands and enhanced integrin outside-in signaling by promoting membrane phosphatidylserine (PS) exposure in vitro. Mechanistically, lipidomics analysis showed that lysophosphatidylcholines were the primary metabolites leading to clustering of HHcy-stimulated platelets. Cytosolic phospholipase A2 (cPLA2) activity and autotaxin (ATX, a secreted lysophospholipase D) secretion were upregulated by Hcy, leading to membrane phospholipid hydrolysis and PS exposure. Moreover, secreted ATX directly interacted with integrin β3. Inhibitors of cPLA2 and ATX activity blocked integrin αIIbβ3 outside-in signaling and thrombosis in HHcy ApoE-/- mice. This study identifies a novel mechanism by which HHcy promotes platelet membrane phospholipid catabolism and extracellular ATX secretion to activate integrin outside-in signaling, consequently to exaggerate thrombosis. This study reveals an innovative approach to treat HHcy-related thrombotic diseases.

scholarly journals An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets

2018 ◽  
Vol 7 (11) ◽  
pp. 440 ◽  
Author(s):  
Wan Lu ◽  
Chi Chung ◽  
Ray Chen ◽  
Li Huang ◽  
Li Lien ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Phospholipase D ◽  
Thrombus Formation ◽  
Human Platelets ◽  
Platelet Activity ◽  
Clot Retraction ◽  
First Time

Phospholipase D (PLD) is involved in many biological processes. PLD1 plays a crucial role in regulating the platelet activity of mice; however, the role of PLD in the platelet activation of humans remains unclear. Therefore, we investigated whether PLD is involved in the platelet activation of humans. Our data revealed that inhibition of PLD1 or PLD2 using pharmacological inhibitors effectively inhibits platelet aggregation in humans. However, previous studies have showed that PLD1 or PLD2 deletion did not affect mouse platelet aggregation in vitro, whereas only PLD1 deletion inhibited thrombus formation in vivo. Intriguingly, our data also showed that the pharmacological inhibition of PLD1 or PLD2 does not affect mouse platelet aggregation in vitro, whereas the inhibition of only PLD1 delayed thrombus formation in vivo. These findings indicate that PLD may play differential roles in humans and mice. In humans, PLD inhibition attenuates platelet activation, adhesion, spreading, and clot retraction. For the first time, we demonstrated that PLD1 and PLD2 are essential for platelet activation in humans, and PLD plays different roles in platelet function in humans and mice. Our findings also indicate that targeting PLD may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders.

Selective inhibition of the platelet phosphoinositide 3-kinase p110β as promising new strategy for platelet protection during extracorporeal circulation

2008 ◽  
Vol 99 (03) ◽  
pp. 609-615 ◽  
Author(s):  
Hans Wendel ◽  
Klaus Dietz ◽  
Daniela Schiebold ◽  
Karlheinz Peter ◽  
Simone Schoenwaelder ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Extracorporeal Circulation ◽  
Ventricular Assist Devices ◽  
Platelet Glycoprotein ◽  
Promising Alternative ◽  
Phosphoinositide 3 Kinase

SummaryExtracorporeal circulation (ECC) is used in cardiac surgery for cardiopulmonary bypass as well as in ventricular assist devices and for extracorporeal membrane oxygenation. Blood contact with the artificial surface and shear stress of ECC activates platelets and leukocytes resulting in a coagulopathy and proinflammatory events. Blockers of the platelet glycoprotein (GP) IIb/IIIa (CD41/CD61) can protect platelet function during ECC, a phenomenon called “platelet anaesthesia”, but may be involved in post-ECC bleeding. We hypothesized that the new selective phosphoinositide 3-kinase p110β inhibitor TGX-221 that inhibits shear-induced platelet activation without prolonging the bleeding time in vivo may also protect platelet function during ECC. Heparinized blood of healthy volunteers (n=6) was treated in vitro with either the GP IIb/IIIa blocker tirofiban, TGX-221 or as control and circulated in an ECC moand after 30 minutes circulation CD41 expression on the ECCtubing as measure for platelet-ECC binding and generation of the platelet activation marker β-thromboglobulin were determined using ELISA. Platelet aggregation and platelet-granulocyte binding were analysed in flow cytometry. After log-transforming the data statistical evaluation was performed using multifactor ANOVA in combination with Tukey’s HSD test (global alpha = 5%).Tirofiban and TGX-221 inhibited platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding. Tirofiban also inhibited ECC-induced β-thromboglobulin release.The observed inhibition of platelet-ECC interaction and platelet activation by tirofiban contributes to explain the mechanism of“platelet anaesthesia”.TGX-221 represents a promising alternative to GP IIb/IIIa blockade and should be further investigated for use during ECC in vivo.

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