The novel steroidal glycoside from the dried bulb of Allium Macrostemon Bunge inhibits platelet activation

2010 ◽  
Vol 34 (8) ◽  
pp. S33-S33
Author(s):  
Wenchao Ou ◽  
Haifeng Chen ◽  
Yun Zhong ◽  
Benrong Liu ◽  
Keji Chen
Keyword(s):  
Platelet Activation ◽  
The Novel ◽  
Steroidal Glycoside ◽  
Allium Macrostemon

scholarly journals Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Blood ◽  
2020 ◽  
Vol 136 (11) ◽  
pp. 1330-1341 ◽  
Author(s):  
Eugenio D. Hottz ◽  
Isaclaudia G. Azevedo-Quintanilha ◽  
Lohanna Palhinha ◽  
Lívia Teixeira ◽  
Ester A. Barreto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Activation ◽  
Ex Vivo ◽  
Invasive Mechanical Ventilation ◽  
The Novel ◽  
Aggregate Formation ◽  
Effector Cells ◽  
Life Threatening ◽  
Emergent Pathogen ◽  
Novel Coronavirus

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregate formation are observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.

The novel P2Y12 antagonist AZD6140 rapidly and reversibly reduces platelet activation in diabetic rats

2010 ◽  
Vol 125 (3) ◽  
pp. e93-e99 ◽  
Author(s):  
Ulrike Flierl ◽  
Corinna Schöpp ◽  
Juliane Jaitner ◽  
Johann Bauersachs ◽  
Andreas Schäfer
Keyword(s):  
Platelet Activation ◽  
Diabetic Rats ◽  
The Novel ◽  
P2y12 Antagonist

Novel Single Agents with Combined Anti-Coagulant and Anti-Platelet Activities: Potential Treatment Option for the Management of HIT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1884-1884
Author(s):  
Jeanine M. Walenga ◽  
Margaret Prechel ◽  
Walter P. Jeske ◽  
Meredith K. McDonald ◽  
James M. Daikur ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Treatment Options ◽  
Clinical Trial Data ◽  
Therapeutic Agents ◽  
Cross Reactivity ◽  
Serotonin Release ◽  
Thrombin Inhibitor ◽  
The Novel ◽  
Anti Platelet Drug ◽  
Fxa Inhibitor

Abstract A recently introduced series of antithrombotic agents brings the novel characteristic of dual anti-coagulant and anti-platelet actions in one molecule. These low molecular weight, synthetic, serine protease inhibitors, depending on structural modifications, have variable ratios of both anti-thrombin and anti-platelet activities. Studies have shown that these agents produce stronger antithrombotic actions relative to single targeted therapeutic agents (O. Iqbal #P0521 and D. Hoppensteadt #OR335, ISTH meeting Sydney, Australia August 2005). Heparin-induced thrombocytopenia (HIT) is an adverse effect of heparin in which both thrombin generation and platelet activation augment hypercoagulable and inflammatory states leading to a high probability of developing severe thrombosis. Current guidelines for patients who have HIT recommend the use of a direct thrombin inhibitor (DTI) to prevent or treat associated thrombosis. Clinical trial data, as well as practice outcomes, show that DTI treatment alone is not sufficient to overcome the pathology and resultant thrombosis in all HIT patients. Thus, more optimal treatment options are needed. A focus of treatment on inhibiting both platelet and coagulation activation is logical based on the pathophysiology of HIT. This study was undertaken to determine if the novel CanAm series of agents may have a role in the management of patients with HIT. Eight agents (MC45301, MC45308, CA207, CA216, CA234, CA247, CA250, CA254) with varying ratios of anticoagulant/anti-platelet activities were studied using the 14C-serotonin release assay (SRA) and flow cytometry for the detection of platelet P-selectin expression and platelet microparticle generation. The DTI argatroban, the FXa inhibitor fondaparinux, and the platelet GPIIb/IIIa receptor antagonist eptifibatide were included for comparison. Both cross-reactivity to HIT antibodies and amelioration of HIT antibody-induced platelet activation were assessed. In the absence of heparin, at 1-100 μg/ml none of the CanAm agents caused platelet activation in the presence of serum from patients with HIT (n=12) ruling out cross-reactivity with HIT antibodies. None of the comparator drugs showed cross reactivity with HIT antibodies. In the presence of heparin (0.1 U/ml) and serum from patients with HIT (n=12), the CanAm agents were able to inhibit all platelet activation responses at concentrations of 10–100 μg/ml. In comparison, the DTI and FXa inhibitor were not able to inhibit the HIT antibody/heparin induced platelet activation with any HIT serum. The GPIIb/IIIa inhibitor, however, showed a concentration-dependent inhibition of the platelet activities with complete blockade at 1 μg/ml, suggesting the importance of platelet activation inhibition for the treatment of HIT. Thus, compared to mono-therapeutic agents such as DTIs and fondaparinux, the dual-acting CanAm agents not only lack cross reactivity with HIT antibodies, but they have the added ability to block the antibody-induced platelet activation that occurs during an acute episode of HIT. A dual-acting anticoagulant/anti-platelet drug may, therefore, be of more value than single targeted anti-thrombin drugs for the management of HIT and associated thrombosis.

scholarly journals COVID-19 Related Cerebrovascular Thromboembolic Complications in Three Young Patients

2020 ◽  
Vol 12 (3) ◽  
pp. 321-328
Author(s):  
Khawaja Hassan Haroon ◽  
Ahmad Muhammad ◽  
Suhail Hussain ◽  
Satya Narayana Patro
Keyword(s):  
Endothelial Dysfunction ◽  
Severe Acute Respiratory Syndrome ◽  
Health Systems ◽  
Platelet Activation ◽  
Young Patients ◽  
The Novel ◽  
Thromboembolic Complications ◽  
Viral Illness

Coronavirus disease 2019 (COVID-19) is a viral illness, caused by the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). It is currently affecting millions of people worldwide and is associated with coagulopathy, both in the venous and arterial systems. The proposed mechanism being excessive inflammation, platelet activation, endothelial dysfunction, and stasis. As an ongoing pandemic declared by WHO in March 2020, health systems worldwide are experiencing significant challenges with COVID-19-related complications. It has been noticed that patients with COVID-19 are at greater risk of thrombosis.

Inhibition of Platelet Activation and Aggregation by Furostanol Saponins Isolated From the Bulbs of Allium macrostemon Bunge

2012 ◽  
Vol 344 (4) ◽  
pp. 261-267 ◽  
Author(s):  
Wen-Chao Ou ◽  
Yun Zhong ◽  
Ben-Rong Liu ◽  
Shi-Ming Liu ◽  
Hai-Feng Chen ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Furostanol Saponins ◽  
Allium Macrostemon

scholarly journals A novel mechanism regulating human platelet activation by MMP-2–mediated PAR1 biased signaling

Blood ◽  
2017 ◽  
Vol 129 (7) ◽  
pp. 883-895 ◽  
Author(s):  
Manuela Sebastiano ◽  
Stefania Momi ◽  
Emanuela Falcinelli ◽  
Loredana Bury ◽  
Marc F. Hoylaerts ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Cleavage Site ◽  
Human Platelet ◽  
The Novel ◽  
Thrombin Cleavage ◽  
Pathway Activation ◽  
Key Points ◽  
Biased Signaling ◽  
Tethered Ligand

Key Points Active MMP-2 enhances platelet activation by cleaving PAR1 at an extracellular site different from the thrombin cleavage site. The novel PAR1-tethered ligand exposed by MMP-2 selectively stimulates PAR1-dependent Gq and G12/13 pathway activation.

scholarly journals Allium macrostemon Saponin Inhibits Activation of Platelet via the CD40 Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Sisi Ling ◽  
Lijun Jin ◽  
Shizheng Li ◽  
Fangcheng Zhang ◽  
Qiong Xu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Platelet Activation ◽  
Allium Macrostemon ◽  
First Time

Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated that saponin exhibited an effect on the TRAF2-mediated ubiquitination degradation, which contributed to the inhibition of the CD40 pathway and its downstream members. The findings determine that A. macrostemon saponin inhibits activation of platelets via activation of downstream proteins of the CD40 pathway. This in turn affected TRAF2-associated ubiquitination degradation and caused an anti-thrombotic effect.

The novel platelet activation receptor CLEC-2

Platelets ◽  
2011 ◽  
Vol 22 (5) ◽  
pp. 380-384 ◽  
Author(s):  
Katsue Suzuki-Inoue ◽  
Osamu Inoue ◽  
Yukio Ozaki
Keyword(s):  
Platelet Activation ◽  
The Novel
Sign in / Sign up

Export Citation Format

Share Document