Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction

Abstract Background A systemic coagulation dysfunction has been associated with COVID-19. In this case report, we describe a COVID-19-positive patient with multisite arterial thrombosis, presenting with acute limb ischaemia and concomitant ST-elevation myocardial infarction and oligo-symptomatic lung disease. Case summary An 83-year-old lady with history of hypertension and chronic kidney disease presented to the Emergency Department with acute-onset left leg pain, pulselessness, and partial loss of motor function. Acute limb ischaemia was diagnosed. At the same time, a routine ECG showed ST-segment elevation, diagnostic for inferior myocardial infarction. On admission, a nasopharyngeal swab was performed to assess the presence of SARS-CoV-2, as per hospital protocol during the current COVID-19 pandemic. A total-body CT angiography was performed to investigate the cause of acute limb ischaemia and to rule out aortic dissection; the examination showed a total occlusion of the left common iliac artery and a non-obstructive thrombosis of a subsegmental pulmonary artery branch in the right basal lobe. Lung CT scan confirmed a typical pattern of interstitial COVID-19 pneumonia. Coronary angiography showed a thrombotic occlusion of the proximal segment of the right coronary artery. Percutaneous coronary intervention was performed, with manual thrombectomy, followed by deployment of two stents. The patient was subsequently transferred to the operating room, where a Fogarty thrombectomy was performed. The patient was then admitted to the COVID area of our hospital. Seven hours later, the swab returned positive for COVID-19. Discussion COVID-19 can have an atypical presentation with thrombosis at multiple sites.

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ACUTE MYOCARDIAL INFARCTION WITH VITAMIN B12 DEFICIENCY AND MILD HYPERHOMOCYSTEINEMIA: A CASE REPORT AND REVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i6.13841 ◽

2016 ◽

Vol 9 (6) ◽

pp. 2

Author(s):

Bijoy Kumar Panda ◽

Siddhi Pramod Umarje ◽

Madhu Bansode

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Vitamin B12 ◽

Antiplatelet Agent ◽

Vitamin B12 Deficiency ◽

Vascular Diseases ◽

Antiplatelet Agents ◽

Adrenergic Blocker ◽

B12 Deficiency ◽

Mild Hyperhomocysteinemia

A 38-year old male was diagnosed with acute myocardial infarction (AMI) without a history of any significant clinical conditions. His subjective complaints and objective findings were clearly suggesting an acute ischemic attack along with vitamin B12 deficiency. While managing him for AMI, serology tests for vitamin B12 revealed low levels along with mild elevation of serum homocysteine level. He was managed with thrombolytic agent, β-adrenergic blocker, aspirin, antiplatelet agents, anticoagulants, statin, vitamin B complex and folic acid supplements. The clinical pharmacist intervened by suggesting discontinuation of Clopidogrel as two antiplatelet agents (Clopidogrel and Ticagrelor) were administered along with an anticoagulant, thereby increasing the risk of bleeding in the patient. Clopidogrel was stopped as Ticagrelor is a better antiplatelet agent when given in combination with low dose aspirin. Also, aspirin dose was reduced to enhance the efficacy of Ticagrelor and provide better secondary prevention for vascular diseases.

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Comparative Studies of an Orally-active Factor Xa Inhibitor, YM-60828, with other Antithrombotic Agents in a Rat Model of Arterial Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615007 ◽

1998 ◽

Vol 79 (02) ◽

pp. 410-416 ◽

Cited By ~ 32

Author(s):

Kazuo Sato ◽

Yumiko Sakai ◽

Fukushi Hirayama ◽

Hiroyuki Koshio ◽

Yuta Taniuchi ◽

...

Keyword(s):

Electrical Stimulation ◽

Arterial Thrombosis ◽

Thrombus Formation ◽

Factor Xa ◽

Test Drug ◽

Antithrombotic Agent ◽

Antithrombotic Activity ◽

Thrombosis Model ◽

Treatment And Prevention ◽

Orally Active

SummaryWe examined the antithrombotic activity of a novel synthetic inhibitor of factor Xa, YM-60828, in an electrically-induced carotid artery thrombosis model in rats. In the first experiment, the antithrombotic activity of YM-60828 after i.v. infusion was compared with those of heparin, darteparin and argatroban. Test drug was administered by i.v. infusion from 30 min before electrical stimulation to the end of the experiment. YM-60828 at 1 mg/kg/h significantly improved patency status, prolonged the time to occlusive thrombus formation and duration of patency. Heparin at 300 U/kg/h also improved these parameters, but were accompanied by a marked increase in systemic coagulation time. In the second experiment, the antithrombotic activity of YM-60828 after oral administration was compared with those of ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate and warfarin. Test drug was orally administered to fasted rats 60 min before electrical stimulation. YM-60828 at 30 mg/kg p.o., but not ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate or warfarin, significantly reduced the incidence of occlusion and improved carotid arterial patency. These results suggest that YM-60828 may be a promising antithrombotic agent for the treatment and prevention of arterial thrombosis which can be given by oral as well as intravenous administration.

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Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

Cardiovascular Research ◽

10.1093/cvr/cvy036 ◽

2018 ◽

Vol 114 (8) ◽

pp. 1178-1188 ◽

Cited By ~ 14

Author(s):

Daniel S Gaul ◽

Julien Weber ◽

Lambertus J van Tits ◽

Susanna Sluka ◽

Lisa Pasterk ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Bone Marrow ◽

Arterial Thrombosis ◽

Ex Vivo ◽

Neutrophil Extracellular Traps ◽

Wild Type ◽

Rotational Thromboelastometry ◽

Extracellular Traps

AbstractAimsSirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI).Methods and resultsUsing a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01).ConclusionsSirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke.

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Infection, inflammation and thrombosis: a review of potential mechanisms mediating arterial thrombosis associated with influenza and severe acute respiratory syndrome coronavirus 2

Biological Chemistry ◽

10.1515/hsz-2021-0348 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Stefan Veizades ◽

Alexandria Tso ◽

Patricia K. Nguyen

Keyword(s):

Myocardial Infarction ◽

Severe Acute Respiratory Syndrome ◽

Arterial Thrombosis ◽

Viral Infections ◽

Respiratory Viruses ◽

Causal Connection ◽

Immune Systems ◽

Clinical Observations ◽

Increased Risk ◽

Time Of Infection

Abstract Thrombosis has long been reported as a potentially deadly complication of respiratory viral infections and has recently received much attention during the global coronavirus disease 2019 pandemic. Increased risk of myocardial infarction has been reported during active infections with respiratory viruses, including influenza and severe acute respiratory syndrome coronavirus 2, which persists even after the virus has cleared. These clinical observations suggest an ongoing interaction between these respiratory viruses with the host’s coagulation and immune systems that is initiated at the time of infection but may continue long after the virus has been cleared. In this review, we discuss the epidemiology of viral-associated myocardial infarction, highlight recent clinical studies supporting a causal connection, and detail how the virus’ interaction with the host’s coagulation and immune systems can potentially mediate arterial thrombosis.

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