• Journal of Applied Biological Chemistry
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• v.63 no.4
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• pp.339-345
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• 2020

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Biomedical Science Letters
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• v.27 no.4
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• pp.270-276
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• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.359-365
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• 2016

Background: Glycoprotein IIb/IIIa (${\alpha}aIIb/{\beta}_3$) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$. Methods: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$, and its final reaction, clot retraction. Results: We found that G-Ro dose-dependently inhibited thrombin-induced platelet aggregation and attenuated the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$ by phosphorylating cyclic adenosine monophosphate (cAMP)-dependently vasodilator-stimulated phosphoprotein (VASP; $Ser^{157}$). In addition, G-Ro strongly abrogated the clot retraction reflecting the intensification of thrombus. Conclusion: We demonstrate that G-Ro is a beneficial novel compound inhibiting ${\alpha}aIIb/{\beta}_3$-mediated fibrinogen binding, and may prevent platelet aggregation-mediated thrombotic disease.

• Journal of Periodontal and Implant Science
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• v.27 no.3
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• pp.597-602
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• 1997

Glanzmann's thrombasthenia is a Qualitative platelet disorder characterized by a deficiency in the platelet membrane glycoproteins IIb/IIIa. It belongs to a group of hereditary platelet disorders typified by normal platelet numbers and a prolonged bleeding time. The severity of bleeding does not correlate with the severity of the platelet glycoprotein IIb/IIIa a abnormality. The present case report describes the periodontal treatment of a patient with Glanzmann's thrombasthenia. A 30-year-old female with a history of Glanzmann's thrombasthenia was referred for gingival bleeding on tooth brushing and discomforts in #38 area. The periodontal finding revealed a diagnosis of localized slight adult periodontitis. Root planing and extraction of #38 was performed under 12 pack of platelets transfusion and digital compression was done for hemostasis. The gingival bleeding ceased within a day in maxilla and 2 days later in mandible. 42 pack of platelets was administered for 3 days of post-treatment and for iron-deficiency anemia 3 pack of RBCs was transfused 2 days later. 1 week later the inflammation in gingiva disappeared and gingival stippling appeared. The clinical result we got was good and in such a medically compromised patient it is an ability to maintain a proper oral hygiene that is essential both for oral and systemic health.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.126-132
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• 2005

Glanzmann's thrombasthenia is an autosomal recessively inherited hemorrhagic disorder that results from quantitative and qualitative abnormalities in platelet membrane glycoprotein IIb-IIIa, also known as ${\alpha}_{IIb}{\beta}_3$ integrin which is an adhesion receptor for fibrinogen and von Willebrand factor. We describe here a 4-year-old girl who had Glanzmann's thrombasthenia with the ${\beta}_3$ subunit missense mutation.

• Korean Journal of Radiology
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• v.20 no.5
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• pp.739-748
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• 2019

For recanalization of emergent large vessel occlusions (ELVOs), endovascular therapy (EVT) using newer devices, such as a stent retriever and large-bore catheter, has shown better patient outcomes compared with intravenous recombinant tissue plasminogen activator only. Intracranial atherosclerotic stenosis (ICAS) is a major cause of acute ischemic stroke, the incidence of which is rising worldwide. Thus, it is not rare to encounter underlying ICAS during EVT procedures, particularly in Asian countries. ELVO due to underlying ICAS is often related to EVT procedure failure or complications, which can lead to poor functional recovery. However, information regarding EVT for this type of stroke is lacking because large clinical trials have been largely based on Western populations. In this review, we discuss the unique pathologic basis of ELVO with underlying ICAS, which may complicate EVT procedures. Moreover, we review EVT data for patients with ELVO due to underlying ICAS and suggest an optimal endovascular recanalization strategy based on the existing literature. Finally, we present future perspectives on this subject.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.99-107
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• 2017

A species of Cordyceps, an ingredient in Chinese traditional medicine well-known for its major component, cordycepin (3'-deoxyadenosine), has been known to have antiplatelet effects; however, its effects on regulation of phosphoprotein have not been fully elucidated. In this study, we investigated how cordycepin regulates the phosphoprotein, including phosphatidylinositol 3-kinase (PI3K)/Akt and p38, to inhibit platelet aggregation, which are concerned with fibrinogen binding to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) and granule secretion in platelets. Our finding suggests that cordycepin inhibits collagen-induced platelet aggregation with $261.1{\mu}M$ of $IC_{50}$ and also inhibits fibrinogen binding to ${\alpha}IIb/{\beta}_3$ by a suppression of PI3K/Akt phosphorylation in a dose dependent manner. In addition, cordycepin further showed to inhibit collagen-induced p38 phosphorylation, reducing granule secretion (i.e. ATP- and serotonin-release) and thromboxane $A_2$ ($TXA_2$) production without regulating cyclooxygenase-1 (COX-1) and thromboxane A synthase (TXAS) activities, as well as phospholipase $C-{\gamma}_2$ ($PLC-{\gamma}_2$) phosphorylation. In conclusion, these results demonstrate that cordycepin-mediated antiplatelet effects were due to the inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ via the suppression of PI3K/Akt phosphorylation and inhibition of granule secretion & $TXA_2$ production by suppressing p38 phosphorylation. These results strongly indicate that cordycepin might have therapeutic or preventive potential for platelet aggregation-mediated disorders, regulating the phosphoprotein, including PI3K/Akt and p38.

• Korean Journal of Clinical Pharmacy
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• v.34 no.2
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• pp.79-99
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• 2024

Background: There was an important revision of the Korean Clinical Practice Guideline for Stroke (KCPGS) for antithrombotic therapy in patients with acute ischemic stroke in 2022. This review is to provide an updated information in this revision. Methods: The revision history by year after the first announcement was examined for each topic, focusing on antithrombotic therapy during acute phase which was revised in 2022. We compared before and after the revision, and investigated the clinical outcomes presented as evidence. It was also compared with the current U.S. guidelines. Results: The major changes about antiplatelet therapy are a clause stating that dual antiplatelet therapy with clopidogrel and aspirin initiated within 24 hours from the stroke onset and maintained for up to 21-30 days is recommended as an acute treatment, as well as the clause that antithrombotic therapy may be initiated within 24 hours after intravenous thrombolytics and that the use of glycoprotein IIb/IIIa receptor antagonists can be considered in highly selected patients as rescue therapy taking into account of benefit and risk. The change to the use of anticoagulants is that it may be reasonable to start oral anticoagulant between 4 and 14 days after stroke onset for patients with acute ischemic stroke and atrial fibrillation. Conclusions: It will be helpful in improving health outcomes for clinical pharmacists to be aware of the latest information for antithrombotic therapy and to actively use it in pharmaceutical care of stroke patients.

• Journal of Korean Neurosurgical Society
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• v.60 no.5
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• pp.518-526
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• 2017

Objective : Thromboembolism is the one of the most serious complications that can occur during endovascular coil embolization of cerebral aneurysm. We report on the effectiveness and safety of intra-arterial/intravenous (IA/IV) glycoprotein IIb/IIIa inhibitor (tirofiban) infusion for treating thromboembolism during endovascular coil embolization of cerebral aneurysm. Methods : We performed a retrospective analysis of 242 patients with ruptured or unruptured cerebral aneurysms (n=264) who underwent endovascular coil embolization from January 2011 to June 2014. Thromboembolism occurred in 20 patients (7.4%), including 14 cases of ruptured aneurysms and 6 cases of unruptured aneurysms. The most common site of aneurysms was the anterior communicating artery (n=8), followed by middle cerebral artery (n=6). When we found an enlarged thromboembolism during coil embolization, we tried to dissolve it using tirofiban administered via IA and IV loading ($5{\mu}g/kg$, respectively) for 3-5 minutes followed by IV maintenance ($0.08{\mu}g/kg/min$) for approximately 4-24 hours. Results : In 4 of 5 patients with total vessel occlusion, the vessel was recanalized to Thrombolysis in Cerebral Infarction Perfusion Scale (TICI) grade 3, and in 1 patient to TICI grade 2a. In 2 patients with partial vessel occlusion and 13 patients with minimal occlusion, the vessel recanalized to TICI grade 3. Irrelevant intracerebral hemorrhage was noted in 1 patient (5%), and thromboemboli-related cerebral infarction developed in 5 patients (25%), of which only 1 (5%) was symptomatic. Conclusion : IA/IV infusion and IV maintenance with tirofiban appear to be an effective rescue treatment for thromboembolism during endovascular coil embolization in patients with ruptured or unruptured cerebral aneurysms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4529-4532
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• 2013

Background: Acute normovolemic hemodilution (ANH) has been widely used to prevent the massive blood loss during hepatic carcinoma. The influences of ANH on coagulation function are still controversy, especially in elderly patients. The study observed ANH effects on coagulation function and fibrinolysis in elderly patients undergoing the disease. Materials and Methods: Thirty elderly patients (aged 60-70 yr) with liver cancer (ASA I or II) taken hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n=15) and control group (n=15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (130/0.4) and Ringer's solution, respectively. Blood samples were drawn from patients in both groups at five different time points: before anesthesia induction (T1), 30 min after ANH (T2), 1 h after start of operation (T3), immediately after operation (T4), and 24 h after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (CD62P and activated GP IIb/GP IIIa) were measured. Results: The perioperative blood loss and allogeneic blood transfusion were recorded during the surgery. The perioperative blood loss was not significantly different between two groups (p>0.05), but the volume of allogeneic blood transfusion in ANH group was significantly less than in control group ($350.0{\pm}70.7$) mL vs. ($457.0{\pm}181.3$) mL (p<0.01). Compared with the data of T1, the prothrombin time (PT) and activated partial thromboplastin time (APTT) measured after T3 were significantly longer (p<0.05) in both groups, but within normal range. There were no significant changes of thrombin time (TT) and D-dimer between two groups at different time points (p>0.05). SFMC and F1+2 increased in both groups, but were not statistically significant. PAC-1-positive cells and CD62P expressions in patients of ANH group were significantly lower than those at T1 (p<0.05) and T2-T5 (p>0.05). Conclusions: ANH has no obvious impact on fibrinolysis and coagulation function in elderly patients undergoing resection of liver cancer. The study suggested that ANH is safe to use in elderly patients and it could reduce allogeneic blood transfusion.