Carotid Artery Thrombus Research Articles

ダビガトランとアスピリン内服で内頸動脈可動性血栓が消失した非弁膜症性心房細動合併アテローム血栓性脳梗塞の1 例

ダビガトランとアスピリン内服で内頸動脈可動性血栓が消失した非弁膜症性心房細動合併アテローム血栓性脳梗塞の1 例

Carotid Artery Thrombus Caused by Severe Iron Deficiency Anemia Induced Reactive Thrombocytosis, Leading to Stroke in a Young Patient

Carotid Artery Thrombus Caused by Severe Iron Deficiency Anemia Induced Reactive Thrombocytosis, Leading to Stroke in a Young Patient

Repetitive Transient Ischaemic Attacks Secondary to a Floating Carotid Artery Thrombus in a Young Patient with Essential Thrombocythemia

AbstractA free-floating carotid artery thrombus is a very rare ultrasonographical finding in patients with acute ischemic cerebrovascular events. One of the main causes of this presentation is represented by the hypercoagulability status of the patients. We report the case of a young male patient who presented with several transient ischaemic attacks secondary to a mobile thrombus in the left carotid sinus. Two hematological abnormalities, essential thrombocytosis and methylene tetrahydrofolate reductase mutation were found to be related to the thrombus formation. The role of the latter in the pathogenesis of ischemic stroke is not well documented in the literature. Following antiplatelet and anticoagulant medication, there was a fast dissolution of the thrombus, followed by a favorable clinical outcome. Neurologists should be aware that young patients with stroke require extensive imagistic and laboratory screening for an accurate etiological diagnosis.

Cerebral Infarct due to Traumatic Carotid Artery Dissection

A patient aged 48 years was admitted to our emergency department with right motor deficit and speech disorder. On neurologic examination, dysarthria, right hemiparesis, and rightside Babinski reflex were found. The patient’s brain computerized tomography (CT) was normal. During hospitalization, he complained of neck pain spreading to the head and was questioned about trauma for the differential diagnosis of dissection. He had been attacked on the left side of his neck during a fight the day before. Twelve hours later, the patient’s symptoms continued to increase and dizziness developed. Diffusion-weighted images revealed a hyper-intensity in the region of the left middle cerebral artery, accompanied by low apparent diffusion coefficient signals (Figure 1). Duplex ultrasound was performed and acute thrombosis and stenosis of the left carotid artery was demonstrated. CT angiography revealed thrombus and dissection of the left carotid artery in the neck (Figure 2A, B, C). Treatment was started with low-molecular-weight heparin followed by warfarin. The patient was prescribed warfarin, an oral anticoagulant, for at least 6 months because the radiologic and duplex ultrasound findings did not change or worsen. Although conventional digital subtraction angiography is still the gold standard procedure, noninvasive methods are preferred to decrease the risk of stroke. Duplex ultrasound has limited ability and is the procedure of choice to follow-up the progression of dissection. CT and magnetic resonance angiography with a similar sensitivity and specificity can be used in the diagnosis of dissection (1,2). In conclusion, internal carotid artery dissection is a potentially life-threatening condition and serious cause of stroke in young patients; therefore, early diagnosis is important.

Extensive Mobile Thrombus of the Internal Carotid Discovered After Intravenous Thrombolysis: What Do I Do Now?

This case report describes a rare presentation of ischemic stroke secondary to an extensive internal carotid artery thrombus, subsequent therapeutic dilemma, and clinical management. A 58-year-old man was administered intravenous (IV) thrombolysis for right middle cerebral artery territory ischemic stroke symptoms. A computed tomography angiogram of the head and neck following thrombolysis showed a longitudinally extensive internal carotid artery thrombus originating at the region of high-grade calcific stenosis. Mechanical embolectomy was deferred because of risk of clot dislodgement and mild neurological symptoms. Recumbency and hemodynamic augmentation were used acutely to support cerebral perfusion. Anticoagulation was started 24 hours after thrombolysis. Carotid endarterectomy was completed successfully within 1 week of presentation. Clinical outcome was satisfactory with discharge modified Rankin Scale score 0. A longitudinally extensive carotid artery thrombus poses a risk of dislodgement and hemispheric stroke. Optimal management in these cases is not known with certainty. In our case, IV thrombolysis, hemodynamic augmentation, delayed anticoagulation, and carotid endarterectomy resulted in a favorable clinical outcome.

Antithrombosis activity of protocatechuic and shikimic acids from functional plant Pinus densiflora Sieb. et Zucc needles.

Pine needle extract (PE) and fermented pine needle extract (FPE) have been reported to show various biological and pharmacological activities such as antioxidant, anti-inflammatory, anti-bacterial, anti-cholesterol, gastrointestinal motility control, and fibrinolytic effect. The aims of our research were to isolate fibrinolytic compounds from PE and FPE and evaluate their antithrombotic activity in vitro and in vivo. Protocatechuic (1) and shikimic (2) acids were isolated and identified from FPE.1 and 2 not only have fibrinolysis activity but also inhibit fibrin formation similar to aspirin. Lysis of fibrin clots by 1 and 2 occurred completely at pH 2-4. Results of SDS-PAGE showed that fibrin polypeptide chains (Aα, Bβ, γ) lysed by 1 and 2 were intact. The antithrombotic effects of 1 and 2 were confirmed by models of carrageenan-induced tail thrombosis, collagen and epinephrine-induced pulmonary thromboembolism in mice, and FeCl3-induced carotid arterial thrombus. Moreover, 1 and 2 did not induce hemorrhage in the tail veins of mice, unlike common antithrombotic compounds. We also measured changes in the quantities of 1 and 2 obtained from FPE. As fermentation progressed, we demonstrated that the quantity of 1 steadily increased, while the quantity of 2 did not significantly change. We therefore demonstrated that FPE is an excellent resource for 1 and 2 and can be produced inexpensively in sufficient quantities for industrial-scale extraction.

History of Carotid Stroke

> [The] two branches which they call carotides or soporales, the sleepy arteries, because they being obstructed, or any way stopt we presently fall asleep. > > —Ambroise Pare (ca. AD 1510–1590)1 Current understanding of carotid artery disease begins in Ancient Greece. The term carotid is derived from the Ancient Greek karos (κάρος), meaning to stupefy. This first description is ascribed to Hippocrates (ca. 460–370 BC) but defined in the later accounts of Rufus of Ephesus (fl. ca. AD 100), who stated that the term was used because superficial compression of the vessels was known to induce stupefaction. The importance of the carotid arteries was even evident in the timeless art of the era. The 31st metope (a rectangular architectural element) from the south side of the Parthenon in Athens (Figure 1) depicts a centaur gripping the neck and compressing the left carotid artery of a Lapith (member of a mythological Thessalian people) during the legendary Centauromachy battle. Galen (ca. AD 131–201) attributed the loss of consciousness to compression not of the carotid arteries but of “sensitive nerves” located proximal to the vessels.2 Today cardiologists recognize a similar syndrome of carotid sinus syncope, tested for through carotid baroreceptor hypersensitivity. Figure 1. The 31st metope from the south side of the Parthenon in Athens. On display in the British Museum, the southern aspect metopes depict the battle between the centaurs (left) and the Lapiths (right) at the wedding of Peirithus, the king of the Lapiths. The left carotid artery of the Lapith is here being intentionally compressed to induce unconsciousness. Photograph courtesy of Colin Howley. Used with permission. The most devastating consequence of carotid artery disease is stroke, which was referred to during classical antiquity as apoplexy. Hippocrates and Galen were both aware that the hemiplegia often accompanying apoplexy resulted from a lesion in …

Cancer-related Stroke due to Mural Thrombus in the Extracranial Carotid Artery

A 41-year-old man was admitted to our hospital because of a cancer-related stroke (CRS) caused by a thrombus of the extracranial carotid artery. He had undergone neoadjuvant radiochemotherapy for metastatic colorectal adenocarcinoma. The serum D-dimer values were within the normal range. We treated him with intravenous unfractionated heparin followed by warfarin. There were no recurrent stroke events over six months. The leading cause of a CRS is an embolism caused by hypercoagulopathy, mainly represented by non-bacterial thrombotic endocarditis. However, it was unusual that, in the current case, a thrombus of the extracranial carotid artery was formed with no significant residual stenosis, thus resulting in an artery-to-artery embolism.

Embolic Stroke due to a Common Carotid Artery Thrombus in a Young Patient with Severe Iron-Deficiency Anemia without Thrombocytosis.

This case report describes a 41-year-old previously healthy male who presented with stuttering transient ischemic symptoms and radiographic evidence of a left common carotid artery thrombus as well as acute and subacute ischemic infarcts in the left middle cerebral artery territory. An exhaustive stroke work-up did not provide a plausible etiology for his symptoms. His complete blood count and iron studies, however, revealed evidence of severe iron-deficiency anemia without reactive thrombocytosis. His stool guaiac test was positive. He was discharged home on oral antithrombotic agents and aggressive iron replacement therapy with a plan for repeat vascular imaging in 3 months and a colonoscopy. This case report suggests that severe iron-deficiency anemia with or without reactive thrombocytosis should be viewed as a possible hematologic condition associated with thrombotic tendencies and a risk factor for ischemic stroke, especially in young adults. Aggressive iron supplementation and short-term antithrombotic therapy with follow-up vascular imaging are a reasonable treatment for these patients.

Antithrombotic Activities of Luteolin In Vitro and In Vivo.

The objectives of present study were to investigate whether luteolin affects procoagulant proteinase activity and fibrin clot formation and influences thrombosis and coagulation in Sprague-Dawle rats. Luteolin significantly inhibited the enzymatic activity of thrombin and FXa activity by 29.1% and 16.2%. Luteolin also inhibited fibrin polymer formation in turbidity and microscopic analysis using fluorescent conjugate. Coagulation assay of luteolin was found to prolong activated partial thromboplastin time and prothrombin time. Moreover, luteolin protected the development of oxidative stress induced thrombosis in the FeCl3 -induced carotid arterial thrombus model. This study demonstrated that luteolin may be useful by reducing or preventing thrombotic challenge and can help us better understand the antithrombotic action of luteolin.

Acral necrosis and upper brachial plexus palsy after prenatal fetal thrombosis

Abstract Intrauterine fetal thrombosis is an extremely rare event with a devastating outcome. The etiology of the condition often remains unclear. A 29-year-old 2nd gravida 1st para presented with mild preeclampsia at 34 weeks of gestation with pathological cardiotocography (CTG), but normal resistance indices in the umbilical and the uterine arteries. The fetal middle cerebral artery (MCA) displayed a significantly reduced pulsatility index (PI). An immediate cesarean section was performed and a male neonate with a birth weight of 2300 g was delivered. Immediately after birth, a progressive necrosis of the neonate’s 4th right final finger link and a palsy of the right brachial plexus were observed. MRI and ultrasound imaging did not display mechanical injuries. The Doppler ultrasound showed a thrombus in the right common carotid and subclavian artery with poststenotic decreased blood flow of the right middle cerebral artery. Further analysis did not reveal inherited or acquired thrombophilias of the neonate. The puzzling prenatal finding of a markedly decreased PI in the MCA as well as the initially suspected postnatal diagnosis of traumatic plexus injury were clarified by the diagnosis of the thrombosis.

Kaempferol inhibits thrombosis and platelet activation.

The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.

Complex interventional treatment in a patient with atrial fibrillation and stroke caused by large carotid artery thrombus: a case report

BackgroundThe treatment option for acute ischaemic stroke depends on the duration of symptoms, the dynamics of neurological condition changes, the aetiology, type of stroke, as well as the results of angiographic and neuroimaging tests.Case presentationA 60-year-old male patient presented with progressive left hemisphere stroke caused by extensive cardiogenic embolism of the common carotid artery and a thrombus closing the internal carotid artery from its ostium to the level of its intracranial division. The complex revascularisation therapy involving surgical embolectomy of the common carotid artery, thrombectomy of the internal carotid artery and intra-arterial thrombolysis has led to the improvement of arterial patency and has countered the progression of acute cerebral ischaemia.ConclusionEmergency carotid embolectomy together with thrombectomy and local thrombolytic rt-PA treatment may be a reasonable rescue therapy for carefully selected patients with large-vessel acute stroke. Further research is needed to establish the advantages and safety of surgical thrombectomy in patients with acute embolic occlusion of the carotid artery and ineffectiveness of or contraindications for systemic thrombolytic treatment.

20-Hydroxyeicosatetraenoic acid involved in endothelial activation and thrombosis.

Endothelial cells play an important role in the process of coagulation and the function of platelets. We have previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite of arachidonic acid, increased platelet aggregation and induced hemostasis. The purpose of the present study is to investigate whether 20-HETE-mediated endothelial activation has effect on the coagulation and platelet aggregation. C57Bl/6 mice were treated with PBS or 20-HETE (20 μg/kg) for 2 h, and then we performed a carotid artery or femoral artery thrombosis model by FeCl3. Detection of blood flow indicated that 20-HETE pretreatment accelerated formation of thrombus in both common carotid artery and femoral artery. In vitro, the secretion and expression of von Willebrand factor (vWF) in cultured human umbilical vein endothelial cells (HUVECs) with 20-HETE stimulation were increased, subsequently. The protein level of vWF in HUVECs was decreased at 1 h but increased with prolonged treatment with 20-HETE (>4 h). In contrast, vWF in the culture medium was increased under administration of 20-HETE at 1 h. As a result, adhesion of platelets on HUVECs was significantly increased by 20-HETE. In HUVECs, the extracellular signal-regulated kinase (ERK) pathway was activated by 20-HETE in a dose-dependent manner, and the inhibitors of ERK and L-type Ca(2+) channel blocked the release of vWF mediated by 20-HETE. In conclusion, 20-HETE instigates endothelial activation and induces the expression and secretion of vWF via the activation of ERK and calcium channel and therefore triggers thrombosis.

Spirulan from blue-green algae inhibits fibrin and blood clots: its potent antithrombotic effects.

We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases.

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway. Methods and Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl₃. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. Conclusion: This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases.

Intraluminal carotid artery thrombus on gadolinium-enhanced MRA

Intraluminal carotid artery thrombus on gadolinium-enhanced MRA

Starase: A bi-functional fibrinolytic protease from hepatic caeca of Asterina pectinifera displays antithrombotic potential

A bi-functional fibrinolytic serine protease, Starase exhibiting thrombolytic potency was purified from hepatic caeca of Asterina pectinifera. Starase showed a single band of approximately 48kDa by SDS-PAGE and fibrin zymography. The N-terminal sequence of Starase was AIPTEFDARTKKHNN, which does not match with any known fibrinolytic enzyme. Starase had optimum amidolytic activity at 50°C and pH 8.0 and the activity was inhibited by PMSF and APMSF. Starase showed the highest specificity toward the substrate H-D-Val-Leu-Lys-pNA for plasmin followed by pyroGlu-Gly-Arg-pNA for urokinase. The apparent Km and Vmax values of Starase toward a chromogenic substrate for plasmin H-D-Val-Leu-Lys-pNA were determined as 1.37mM and 6.8mM/min/mg respectively. The fibrinolytic activity of Starase by fibrin plate assay displayed that it could not only directly degrade fibrin clot but also activate plasminogen. Starase showed a strong fibrinogenolytic activity, cleaving all three major chains of fibrinogen rapidly. In addition, Starase with more than 1μg could cleave extracellular matrix component type VII collagen, and plasma proteins such as bovine albumin and bovine gamma globulin. It could also inhibit factor Xa and thrombin activity. Starase at a dose of 0.8mg/kg was devoid of hemorrhagic activity and it demonstrated antithrombotic effect in three animal models; FeCl2-induced carotid arterial thrombus model, carrageenan-induced tail thrombosis model and collagen and epinephrine induced pulmonary thromboembolism mice model. These results suggest that Starase has the potential to be a potent thrombolytic agent due to its bi-functional properties (containing both direct-acting and plasminogen-activating activities) and lack of hemorrhagic activity. Although Starase might interfere with the normal composition of the plasma proteins, it may be used not only for the treatment and prevention of thrombosis, but also in a number of biomedical applications.

Short- and long-term treatment with folic acid suppresses thrombus formation in atherogenic mice in vivo

In the present study, we examined the effects of short- and long-term treatment with folic acid (FA) on thrombus formation in vivo in atherogenic mice to explore a novel agent for the prevention of atherothrombotic disease. Apolipoprotein E and low-density lipoprotein receptor double deficient (ApoE−/−LDLR−/−) mice were orally administrated a single bolus of FA (20mg/kg) or fed an atherogenic diet with or without FA (0.02, 0.5, and 1.5mg/kg) for 12 weeks. Thrombus formation and endothelial function were assessed in vivo using the He–Ne laser-induced carotid artery thrombus formation test and the flow-mediated vasodilation method. Platelet reactivity was assessed ex vivo using haemostatometry. Short-term treatment with FA markedly increased plasma folate levels and significantly suppressed laser-induced thrombus formation in apoE−/−LDLR−/− mice. Short-term treatment with FA suppressed platelet reactivity in apoE−/−LDLR−/− mice, but FA treatment did not affect endothelial function or plasma homocysteine levels. Long-term treatment with FA increased plasma folate levels dose-dependently. Thrombus formation and endothelial dysfunction were suppressed by treatment with 0.5 and 1.5mg/kg of FA, respectively, but not with 0.02mg/kg of FA, whereas platelet reactivity was not altered by treatment with any dose of FA. Long-term treatment with all doses of FA decreased the plasma homocysteine levels in apoE−/−LDLR−/− mice, although this result was not consistent with its anti-thrombotic action. In conclusion, our data showed that short- and long-term treatment with FA could suppress in vivo thrombus formation in an atherogenic setting, independent of its hypohomocysteinemic action.

Can Shape Analysis Differentiate Free-floating Internal Carotid Artery Thrombus from Atherosclerotic Plaque in Patients Evaluated with CTA for Stroke or Transient Ischemic Attack?

Patients presenting with transient ischemic attack or stroke may have symptom-related lesions on acute computed tomography angiography (CTA) such as free-floating intraluminal thrombus (FFT). It is difficult to distinguish FFT from carotid plaque, but the distinction is critical as management differs. By contouring the shape of these vascular lesions ("virtual endarterectomy"), advanced morphometric analysis can be performed. The objective of our study is to determine whether quantitative shape analysis can accurately differentiate FFT from atherosclerotic plaque. We collected 23 consecutive cases of suspected carotid FFT seen on CTA (13 men, 65 ± 10 years; 10 women, 65.5 ± 8.8 years). True-positive FFT cases (FFT+) were defined as filling defects resolving with anticoagulant therapy versus false-positives (FFT-), which remained unchanged. Lesion volumes were extracted from CTA images and quantitative shape descriptors were computed. The five most discriminative features were used to construct receiver operator characteristic (ROC) curves and to generate three machine-learning classifiers. Average classification accuracy was determined by cross-validation. Follow-up imaging confirmed sixteen FFT+ and seven FFT- cases. Five shape descriptors delineated FFT+ from FFT- cases. The logistic regression model produced from combining all five shape features demonstrated a sensitivity of 87.5% and a specificity of 71.4% with an area under the ROC curve = 0.85 ± 0.09. Average accuracy for each classifier ranged from 65.2%-76.4%. We identified five quantitative shape descriptors of carotid FFT. This shape "signature" shows potential for supplementing conventional lesion characterization in cases of suspected FFT.