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Spontaneous isolated dissection of the iliac artery (SID-IA) is a rare vascular condition typically associated with trauma or connective tissue disorders. We present a unique case of a 39-year-old male without known risk factors or trauma history who presented with lower abdominal pain. Diagnostic imaging revealed SID-IA involving the right external iliac artery with thrombus formation. Despite negative findings for connective tissue disorders, the patient underwent successful endovascular stenting following initial medical management. Vigilance in diagnosis and prompt intervention are crucial in managing SID-IA to prevent complications such as limb ischemia and aneurysm formation. This case emphasizes the importance of considering SID-IA in young patients presenting with abdominal pain, even in the absence of traditional risk factors, and highlights evolving treatment options for this rare condition.

High perioperative mortality and complication rates during the coronavirus disease 2019 (COVID-19) pandemic have been reported. In head and neck reconstruction, not only is patient safety important, but the prevention of infection introduced by the surgical team is also important because the procedure is performed in close proximity to the upper respiratory tract. In addition, recent studies have reported an increased risk for thrombus formation after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 vaccination, which is problematic for microsurgical reconstruction procedures. At the authors' institution, patients undergoing head and neck reconstruction are requested to stay home for 2 weeks and undergo screening tests for COVID-19 before admission. Surgeons use standard personal protective equipment during surgery. There was no significant difference in the rate of total flap necrosis between the COVID-19 and non-pandemic periods or large difference of perioperative complication rates between vaccinated and non-vaccinated patients. No surgery-related infections among the surgical staff were also found. [ABSTRACT FROM AUTHOR]

Liver failure and cirrhosis are characterized by abnormal hemostasis with aberrant platelet activation. In particular, the consequences of cholestatic liver disease and molecular mechanisms, including the role of bile acids leading to impaired platelet responses, are not well understood. Here, we demonstrate that bile acids inhibit human and murine platelet activation, adhesion and spreading, leading to reduced thrombus formation under flow conditions. We identified the G-protein coupled receptor TGR5 in platelets and provide support for its role as mediator of bile acid-induced impairment of platelet activation. In the liver, TGR5 couples to Gαs proteins, activates the adenylate cyclase to induce a transient cAMP rise and stimulates the MAPK signaling pathway to regulate cholangiocyte proliferation, hepatocyte survival and inflammation. In this report, we demonstrate that the genetic deficiency of TGR5 in mice led to enhanced platelet activation and thrombus formation, suggesting that TGR5 plays an important role in hemostasis. Mechanistically, platelet inhibition is achieved by TGR5 mediated PKA activation and modulation of AKT and ERK1/2 phosphorylation. Thus, this report provides evidence for the ability of TGR5 ligands to reduce platelet activation and identifies TGR5 agonism as a new target for the prevention of cardiovascular diseases.

Abstract Stroke is an acute cerebrovascular disease in which blood flow to the brain is suddenly disrupted, causing damage to nerve cells. It involves complex and diverse pathophysiological processes and the treatment strategies are also diverse. The treatment for patients with stroke and atrial fibrillation (AF) is aimed at suppressing thrombus formation and migration. However, information regarding the protein networking involved in different thrombus formation pathways in patients with AF and stroke is insufficient. We performed protein profiling of patients with ischemic stroke with and without AF to investigate the mechanisms of thrombus formation and its pathophysiological association while providing helpful information for treating and managing patients with AF. These two groups were compared to identify the protein networks related to thrombus formation in AF. We observed that patients with ischemic stroke and AF had activated inflammatory responses induced by C-reactive protein, lipopolysaccharide-binding protein, and alpha-1-acid glycoprotein 1. In contrast, thyroid hormones were increased due to a decrease in transthyretin and retinol-binding protein 4 levels. The mechanism underlying enhanced cardiac activity, vasodilation, and the resulting thrombosis pathway were confirmed in AF. These findings will play an essential role in improving the prevention and treatment of AF-related stroke.

Stroke is an acute cerebrovascular disease in which blood flow to the brain is suddenly disrupted, causing damage to nerve cells. It involves complex and diverse pathophysiological processes and the treatment strategies are also diverse. The treatment for patients with stroke and atrial fibrillation (AF) is aimed at suppressing thrombus formation and migration. However, information regarding the protein networking involved in different thrombus formation pathways in patients with AF and stroke is insufficient. We performed protein profiling of patients with ischemic stroke with and without AF to investigate the mechanisms of thrombus formation and its pathophysiological association while providing helpful information for treating and managing patients with AF. These two groups were compared to identify the protein networks related to thrombus formation in AF. We observed that patients with ischemic stroke and AF had activated inflammatory responses induced by C-reactive protein, lipopolysaccharide-binding protein, and alpha-1-acid glycoprotein 1. In contrast, thyroid hormones were increased due to a decrease in transthyretin and retinol-binding protein 4 levels. The mechanism underlying enhanced cardiac activity, vasodilation, and the resulting thrombosis pathway were confirmed in AF. These findings will play an essential role in improving the prevention and treatment of AF-related stroke. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) poses a significant risk of stroke due to thrombus formation, which primarily occurs in the left atrial appendage (LAA). Medical image‐based computational fluid dynamics (CFD) simulations can provide valuable insight into patient‐specific hemodynamics and could potentially enhance personalized assessment of thrombus risk. However, the importance of accurately representing the left atrial (LA) wall dynamics has not been fully resolved. In this study, we compared four modeling scenarios; rigid walls, a generic wall motion based on a reference motion, a semi‐generic wall motion based on patient‐specific motion, and patient‐specific wall motion based on medical images. We considered a LA geometry acquired from 4D computed tomography during AF, systematically performed convergence tests to assess the numerical accuracy of our solution strategy, and quantified the differences between the four approaches. The results revealed that wall motion had no discernible impact on LA cavity hemodynamics, nor on the markers that indicate thrombus formation. However, the flow patterns within the LAA deviated significantly in the rigid model, indicating that the assumption of rigid walls may lead to errors in the estimated risk factors. In contrast, the generic, semi‐generic, and patient‐specific cases were qualitatively similar. The results highlight the crucial role of wall motion on hemodynamics and predictors of thrombus formation, and also demonstrate the potential of using a generic motion model as a surrogate for the more complex patient‐specific motion. While the present study considered a single case, the employed CFD framework is entirely open‐source and designed for adaptability, allowing for integration of additional models and generic motions. [ABSTRACT FROM AUTHOR]

Thrombosis is the main reason for the failure of ventricular assist devices (VADs). It has been acknowledged that the platelet activation induced by the nonphysiological blood flow leads to the increased thrombotic risk. However, due to the complicated influence of the VADs' flow field and the difficulty in real‐time in situ observation, the mechanisms and process of thrombus formation in VADs remain unclear. In this work, the process of thrombus formation in VADs in vitro experiments is observed. The thrombus is found to form on the middle of the inlet guide vanes first and it is mainly caused by the immediate activation of platelets induced by the high shear rate of the flow field around the vanes and also affected by the rotation of the impeller. Then, subsequent thrombus is found in the tail of guide vanes and around the axle journal, where the blood flow is stagnated and the platelets are activated by the accumulated bioagonists. These findings clarify that the thrombus formed on the inlet guide vanes and the axle journal are dominated by two different mechanisms. This work provides unique insights into the initial formation of the thrombus on VADs and helps to reduce the thrombotic risk. [ABSTRACT FROM AUTHOR]

Abstract Background Von Willebrand factor (VWF) and factor VIII (FVIII) complex play a pivotal role in hemostasis. A deficiency or defect of VWF causes von Willebrand disease (VWD). Recombinant (r)VWF product has proved to be effective for hemostatic treatment of VWD, but limited information is available on their role in moderating thrombus formation under flow condition. We aimed to assess thrombus formation in the presence of rVWF combined with rFVIII or pegylated-extended half-life rFVIII (peg-EHL-rFVIII) in VWD whole blood under high shear flow. Methods Perfusion chamber experiments under high shear (2,500 s− 1) combined with immunostaining were performed using patient’s whole blood with type 1 VWD, mixed with rVWF (Vonvendi®; 1.6 IU/mL), rFVIII or peg-EHL-rFVIII (Advate® or Adynovate®; 1.0 IU/mL), or both. Similar experiments were also conducted with clinical medical devices (T-TAS®). Results The addition of rFVIII did not augment thrombus formation assessed by surface coverage (SC) and thrombus height (TH), whereas rVWF enhanced these parameters (SC 19.1 ± 1.1% vs. 30.1 ± 4.1%, TH 2.2 ± 0.14 μm vs. 3.6 ± 0.40 μm, respectively). The co-presence of rVWF/rFVIII was comparable to plasma-derived VWF/FVIII (Confact®, VWF:FVIII ratio = 1.6:1.0) for increasing thrombogenicity in SC (32.5 ± 4.3% vs. 38.7 ± 5.5%) and in TH (5.0 ± 0.60 μm vs. 5.5 ± 0.64 μm), respectively. The pre-incubation time with rVWF and rFVIII appeared to have a little effect on the size of thrombus. Peg-EHL-rFVIII mediated thrombus formation to similar extent as rFVIII in the co-presence of rVWF. Similar results were obtained even with T-TAS. Immunostaining demonstrated that rFVIII and peg-EHL-rFVIII were similarly co-localized with rVWF in formed thrombi, indicating that pegylation did not interfere with molecular complexes. Conclusion The effects of high-level rVWF and peg-EHL-rFVIII on thrombus formation were comparable to conventional therapeutic products in a patient’s whole blood with VWD under high shear flow.

Abstract Thrombosis is the main reason for the failure of ventricular assist devices (VADs). It has been acknowledged that the platelet activation induced by the nonphysiological blood flow leads to the increased thrombotic risk. However, due to the complicated influence of the VADs’ flow field and the difficulty in real‐time in situ observation, the mechanisms and process of thrombus formation in VADs remain unclear. In this work, the process of thrombus formation in VADs in vitro experiments is observed. The thrombus is found to form on the middle of the inlet guide vanes first and it is mainly caused by the immediate activation of platelets induced by the high shear rate of the flow field around the vanes and also affected by the rotation of the impeller. Then, subsequent thrombus is found in the tail of guide vanes and around the axle journal, where the blood flow is stagnated and the platelets are activated by the accumulated bioagonists. These findings clarify that the thrombus formed on the inlet guide vanes and the axle journal are dominated by two different mechanisms. This work provides unique insights into the initial formation of the thrombus on VADs and helps to reduce the thrombotic risk.

Liver failure and cirrhosis are characterized by abnormal hemostasis with aberrant platelet activation. In particular, the consequences of cholestatic liver disease and molecular mechanisms, including the role of bile acids leading to impaired platelet responses, are not well understood. Here, we demonstrate that bile acids inhibit human and murine platelet activation, adhesion and spreading, leading to reduced thrombus formation under flow conditions. We identified the G-protein coupled receptor TGR5 in platelets and provide support for its role as mediator of bile acid-induced impairment of platelet activation. In the liver, TGR5 couples to Gαs proteins, activates the adenylate cyclase to induce a transient cAMP rise and stimulates the MAPK signaling pathway to regulate cholangiocyte proliferation, hepatocyte survival and inflammation. In this report, we demonstrate that the genetic deficiency of TGR5 in mice led to enhanced platelet activation and thrombus formation, suggesting that TGR5 plays an important role in hemostasis. Mechanistically, platelet inhibition is achieved by TGR5 mediated PKA activation and modulation of AKT and ERK1/2 phosphorylation. Thus, this report provides evidence for the ability of TGR5 ligands to reduce platelet activation and identifies TGR5 agonism as a new target for the prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes. In this review, plaque phenotype is discussed in relation to thrombus composition, and an overview of important mediators (haemodynamics, matrix components, and soluble factors) in plaque-induced platelet activation is given. As thrombus formation on disrupted plaques does not necessarily result in complete vessel occlusion, plaque healing can occur. Therefore, the latest findings on plaque healing and the potential role of platelets in this process are summarized. Finally, the clinical need for more effective antithrombotic agents is highlighted. [ABSTRACT FROM AUTHOR]

Background: Von Willebrand factor (VWF) and factor VIII (FVIII) complex play a pivotal role in hemostasis. A deficiency or defect of VWF causes von Willebrand disease (VWD). Recombinant (r)VWF product has proved to be effective for hemostatic treatment of VWD, but limited information is available on their role in moderating thrombus formation under flow condition. We aimed to assess thrombus formation in the presence of rVWF combined with rFVIII or pegylated-extended half-life rFVIII (peg-EHL-rFVIII) in VWD whole blood under high shear flow. Methods: Perfusion chamber experiments under high shear (2,500 s− 1) combined with immunostaining were performed using patient's whole blood with type 1 VWD, mixed with rVWF (Vonvendi®; 1.6 IU/mL), rFVIII or peg-EHL-rFVIII (Advate® or Adynovate®; 1.0 IU/mL), or both. Similar experiments were also conducted with clinical medical devices (T-TAS®). Results: The addition of rFVIII did not augment thrombus formation assessed by surface coverage (SC) and thrombus height (TH), whereas rVWF enhanced these parameters (SC 19.1 ± 1.1% vs. 30.1 ± 4.1%, TH 2.2 ± 0.14 μm vs. 3.6 ± 0.40 μm, respectively). The co-presence of rVWF/rFVIII was comparable to plasma-derived VWF/FVIII (Confact®, VWF:FVIII ratio = 1.6:1.0) for increasing thrombogenicity in SC (32.5 ± 4.3% vs. 38.7 ± 5.5%) and in TH (5.0 ± 0.60 μm vs. 5.5 ± 0.64 μm), respectively. The pre-incubation time with rVWF and rFVIII appeared to have a little effect on the size of thrombus. Peg-EHL-rFVIII mediated thrombus formation to similar extent as rFVIII in the co-presence of rVWF. Similar results were obtained even with T-TAS. Immunostaining demonstrated that rFVIII and peg-EHL-rFVIII were similarly co-localized with rVWF in formed thrombi, indicating that pegylation did not interfere with molecular complexes. Conclusion: The effects of high-level rVWF and peg-EHL-rFVIII on thrombus formation were comparable to conventional therapeutic products in a patient's whole blood with VWD under high shear flow. [ABSTRACT FROM AUTHOR]

Thrombus formation is highly dependent upon the physico-chemical environment in which it is triggered. Our ability to understand how thrombus formation is initiated, regulated, and resolved in the human body is dependent upon our ability to replicate the mechanical and biological properties of the arterial wall. Current in vitro thrombosis models principally use reductionist approaches to model the complex biochemical and cellular milieu present in the arterial wall, and so researcher have favored the use of in vivo models. The field of vascular tissue engineering has developed a range of techniques for culturing artificial human arteries for use as vascular grafts. These techniques therefore provide a basis for developing more sophisticated 3D replicas of the arterial wall that can be used in in vitro thrombosis models. In this review, we consider how tissue engineering approaches can be used to generate 3D models of the arterial wall that improve upon current in vivo and in vitro approaches. We consider the current benefits and limitations of reported 3D tissue engineered models and consider what additional evidence is required to validate them as alternatives to current in vivo models. [ABSTRACT FROM AUTHOR]

Summary: Abnormalities of platelet function were reported in patients with severe COVID‐19 (severe‐C), but few data are available in patients with mild COVID‐19 (mild‐C) and after COVID‐19 recovery. The aim of this study was to investigate platelet parameters in mild‐C patients (n = 51), with no evidence of pneumonia, and severe‐C patients (n = 49), during the acute phase and after recovery, compared to 43 healthy controls. Both mild‐C and severe‐C patients displayed increased circulating activated platelets, low δ‐granule content (ADP, serotonin), impaired platelet activation by collagen (light transmission aggregometry) and impaired platelet thrombus formation on collagen‐coated surfaces under controlled flow conditions (300/s shear rate). The observed abnormalities were more marked in severe‐C patients than in mild‐C patients. Overall, 61% (30/49) of mild‐C and 73% (33/45) of severe‐C patients displayed at least one abnormal platelet parameter. In a subgroup of just 13 patients who showed no persisting signs/symptoms of COVID‐19 and were re‐evaluated at least 1 month after recovery, 11 of the 13 subjects exhibited normalization of platelet parameters. In conclusion, mild abnormalities of platelet parameters were present not only in severe‐C but also, albeit to a lesser extent, in mild‐C patients during the acute phase of COVID‐19 and normalized in most tested patients after clinical recovery. [ABSTRACT FROM AUTHOR]

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVImediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxininduced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagenadrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified. [ABSTRACT FROM AUTHOR]

Aortic dissection (AD) has a high mortality rate. About 40% of the people with type B AD do not live for more than a month. The prognosis of AD is quite challenging. Hence, we present a triphasic model for the formation and growth of thrombi using the theory of porous media (TPM). The whole aggregate is divided into solid, liquid and nutrient constituents. The constituents are assumed to be materially incompressible and isothermal, and the whole aggregate is assumed to be fully saturated. Darcy's law describes the flow of fluid in the porous media. The regions with thrombi formation are determined using the solid volume fraction. The velocity- and nutrient concentration-induced mass exchange is defined between the nutrient and solid phases. We introduce the set of equations and a numerical example for thrombosis in type B AD. Here we study the effects of different material parameters and boundary conditions. We choose the values that give meaningful results and present the model's features in agreement with the Virchow triad. The simulations show that the thrombus grows in the low-velocity regions of the blood. We use a realistic 2-d geometry of the false lumen and present the model's usefulness in actual cases. The proposed model provides a reasonable approach for the numerical simulation of thrombosis. [ABSTRACT FROM AUTHOR]

Background. The stage 4 mitral stenosis is accompanied by atrial fibrillation which significantly worsens the prognosis due to the possibility of thromboembolic complications. However, sinus rhythm does not exclude the possibility of thrombosis which sometimes requires differential diagnosis with heart tumors. The aim. To present a case of unusual thrombus formation in a patient with significant mitral stenosis on the background of sinus rhythm and describe the specifics of determining indications for surgical intervention. Case report. Female patient K., 42 years old, who was admitted on January 12, 2023 to the National Amosov Institute of Cardiovascular Surgery, had been suffering from rheumatism for the past 20 years. In this case, the clinical course of mitral stenosis could be classified as stage 4, since there were signs of severe heart failure (shortness of breath on light exertion, peripheral edema, right-sided pleuritis, pulmonary thrombosis). However, the patient had sinus rhythm, which is more characteristic of the stage 3 mitral stenosis. The patient underwent mitral valve prosthetic surgery and removal of an unusual thrombus from the pulmonary valve cavity on January 23, 2023. Conclusions. The course of mitral stenosis, despite its thorough study, may have unusual clinical and instrumental manifestations, which requires differential diagnosis with heart tumors and other diseases. In some cases, the mechanism of thrombus formation can be extremely unusual, which can be a subject for discussion by cardiologists.

Leukocyte-platelet adhesion during hypoxia, tissue damage, activation of inflammation and coagulation is associated with the expression of ICAM-1 membrane molecules and integrins by blood and tissue cells. At the same time, platelet adhesion receptors determine their adhesion to the endothelium and recruited lymphocytes. The role of platelets in the pathogenesis of ischemic cardiovascular diseases also consists in their ability to modulate both hemostasis and inflammatory reactions, which is accompanied by the secretion of inflammatory mediators and factors that promote the recruitment of leukocytes to tissue damage sites. Purpose of the study: to study the effect of the synthetic glucocorticoid dexamethasone on the expression of adhesion receptors CD18+ and CD54+ on leukocytes, the content of platelets and fibrinogen in the blood of patients with ALLI, the relationship of these indicators with the severity and outcome of the disease.To study the effect of anti-inflammatory therapy, a group of 32 patients treated with dexamethasone was formed; the comparison group was represented by 71 patients with basic therapy, the control group consisted of 15 volunteers. After revascularization, all patients received antiplatelet and anticoagulant therapy. Dexamethasone infusions were carried out in a course of 4 to 6 days after reconstructive surgery. In all patients, the content of C-reactive protein in the blood, the content of platelets and fibrinogen were determined. The number of lymphocytes expressing adhesion molecules ICAM-1 (CD54+) and integrins (CD18+) was counted using the immunocytochemical method. Studies were performed before surgery and on days 1, 3, 7, and 10 after surgery.With exacerbation of ischemia and damage to the endothelium, the accumulation of cytolysis products, the expression of adhesion molecules increases both on endotheliocytes and on inflammatory effector cells – leukocytes and platelets. Adhesion molecules conduct an activation signal inside the cell, which promotes adhesion of leukocytes and platelets to the endothelium, lymphocytic-platelet adhesion, the formation of a parietal thrombus, and possible occlusion of damaged vessels. Increased expression of adhesion molecules is associated with the activation of metabolism, inflammation, coagulation and oxidative stress, stimulates all hematopoietic lineages, including platelets. The level of involvement of cellular reactions in the pathogenesis of the disease affects the effectiveness and duration of treatment, the risk of recurrent thrombosis and death. Anti-inflammatory therapy with dexamethasone contributed to earlier remission, a decrease in the proportion of infectious complications, such as wound suppuration from 10% to 6%, the number of necessary amputations from 32% to 16%, the frequency of deaths from 31% to 6%, and a reduction in hospital stay from 13 days to 10.Inflammation, adhesiveness of effector cells and thrombosis are important factors in the pathogenesis of acute lower limb ischemia. Therapy with dexamethasone helps to reduce the level of systemic inflammatory response, the number of necessary amputations, the number of complications and adverse outcomes in the treatment of ALLI, and reduce the length of stay in the hospital.

Abstract Background Postoperative cerebral infarction is a rare but serious complication after lung cancer surgery. We aimed to investigate the risk factors and evaluate the efficiency of our devised surgical procedure to prevent cerebral infarction. Methods We retrospectively examined 1,189 patients who underwent a single lobectomy for lung cancer at our institution. We identified the risk factors for cerebral infarction and investigated the preventive effects of performing resection of the pulmonary vein as the last step of the surgical procedure during left upper lobectomy. Results Among the 1,189 patients, we identified 5 male patients (0.4%) with postoperative cerebral infarction. All five underwent left-sided lobectomy including three upper and two lower lobectomies. Left-sided lobectomy, a lower forced expiratory volume in 1 s, and lower body mass index were associated with postoperative cerebral infarction (Ps

Abstract Background Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus. Methods (1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA. Results The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806–5.500; p

Abstract In this study, we present a method to quantitatively analyze the thrombus formation process through image analysis in an in vitro thrombus model with a circular cross section. The thrombus model used was designed based on the mechanism between the physical principle of wall shear rate (WSR) and thrombus formation. Image analysis was used to help visualize the thrombus formation process and calculate the thrombus area. Through this method, the thrombus formation and growth from the channel wall was demonstrated without the use of fluorescence. In addition, by dividing the image into sub-sections, the accuracy of the thrombus growth pattern was improved. The departing blood clots which are called embolus, were observed being separated from the thrombus.

Atrial fibrillation (AF) is a common cardiac arrhythmia characterized by irregular and rapid electrical activity in the atria, leading to ineffective contraction and poor blood flow. More than 90% of the left atrial (LA) thrombi that cause thromboembolic events during atrial fibrillation (AF) develop in the left atrial appendage (LAA). AF modifies the hemodynamics of the left atrium, which can result in thrombosis of the LAA, systemic embolism, and stroke. The current options to reduce thromboembolic events are oral anticoagulation, surgical LAA exclusion, or percutaneous LAA occlusion. However, the mechanism underlying thrombus development in the LAA remains poorly understood. Computational fluid dynamics (CFD) analysis can be used to better understand the risk of thrombus formation and subsequent embolic events. CFD enables the simulation and visualization of blood flow patterns within the heart, including complex structures such as the LAA. Using CFD, researchers can analyze the hemodynamics of blood flow, identify areas of stagnation or turbulence, and predict the risk of thrombus formation. The correlation between blood flow dynamics, atrial fibrillation, and the risk of stroke has been highlighted by CFD studies investigating the underlying mechanism of thrombus formation in the LAA. This review study intends to provide a comprehensive overview of the factors involved in thrombus formation and their implications for clinical practice by synthesizing the insights acquired from these CFD studies. [ABSTRACT FROM AUTHOR]

When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis, but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis. This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl3-induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions. [ABSTRACT FROM AUTHOR]

Type B aortic dissection (TBAD) carries a high risk of complications, particularly with a partially thrombosed or patent false lumen (FL). Therefore, uncovering the risk factors leading to FL thrombosis is crucial to identify high-risk patients. Although studies have shown that morphological parameters of the dissected aorta are related to FL thrombosis, often conflicting results have been reported. We show that recent models of thrombus evolution in combination with sensitivity analysis methods can provide valuable insights into how combinations of morphological parameters affect the prospect of FL thrombosis. Based on clinical data, an idealized geometry of a TBAD is generated and parameterized. After implementing the thrombus model in computational fluid dynamics simulations, a global sensitivity analysis for selected morphological parameters is performed. We then introduce dimensionless morphological parameters to scale the results to individual patients. The sensitivity analysis demonstrates that the most sensitive parameters influencing FL thrombosis are the FL diameter and the size and location of intimal tears. A higher risk of partial thrombosis is observed when the FL diameter is larger than the true lumen diameter. Reducing the ratio of the distal to proximal tear size increases the risk of FL patency. In summary, these parameters play a dominant role in classifying morphologies into patent, partially thrombosed, and fully thrombosed FL. In this study, we point out the predictive role of morphological parameters for FL thrombosis in TBAD and show that the results are in good agreement with available clinical studies. [ABSTRACT FROM AUTHOR]

Paclitaxel is a microtubule-stabilizing drug used to treat several types of cancer, including ovarian and breast cancer. Because of its antiproliferative effect on vascular smooth muscle cells, balloons and stents are coated with paclitaxel for use in coronary revascularization and prevention of in-stent restenosis (ISR). However, mechanisms underlying ISR are complicated. Platelet activation is one of the major causes of ISR after percutaneous coronary intervention. Although the antiplatelet activity of paclitaxel was noted in rabbit platelets, the effect of paclitaxel on platelets remains unclear. This study investigated whether paclitaxel exhibits antiplatelet activity in human platelets. Paclitaxel inhibited platelet aggregation induced by collagen but not that induced by thrombin, arachidonic acid, or U46619, suggesting that paclitaxel is more sensitive to the inhibition of collagen-induced platelet activation. Moreover, paclitaxel blocked collagen receptor glycoprotein (GP) VI downstream signaling molecules, including Lyn, Fyn, PLCγ2, PKC, Akt, and MAPKs. However, paclitaxel did not directly bind to GPVI and cause GPVI shedding, as detected by surface plasmon resonance and flow cytometry, respectively, indicating that paclitaxel may interfere with GPVI downstream signaling molecules, such as Lyn and Fyn. Paclitaxel also prevented granule release and GPIIbIIIa activation induced by collagen and low convulxin doses. Moreover, paclitaxel attenuated pulmonary thrombosis and delayed platelet thrombus formation in mesenteric microvessels without significantly affecting hemostasis. Paclitaxel exerts antiplatelet and antithrombotic effects. Thus, paclitaxel may provide additional benefits beyond its antiproliferative effect when used in drug-coated balloons and drug-eluting stents for coronary revascularization and prevention of ISR. [Display omitted] • Platelet activation is involved in thrombosis and in-stent restenosis. • Paclitaxel-coated balloon and -eluting stent used for coronary revascularization • Paclitaxel exerts antiplatelet and antithrombotic activities. • Paclitaxel's antiplatelet effects also contribute to preventing in-stent restenosis. [ABSTRACT FROM AUTHOR]

Thrombus formation on a well-conserved bicuspid aortic valve is rare. We encountered a patient with organized thrombus formation on a native bicuspid aortic valve without calcification or stenosis, which was found occasionally during an elective operation for ascending aorta replacement surgery. The location of the thrombus was just at the orifice of left coronary artery, which produced the atherosclerosis-like symptoms such like exertional chest tightness and dyspnea. And these are no apparent predisposing causes of thrombosis could be ascertained postoperatively. The patient is in excellent condition 6 months after the operation. The lesson we learned from our case is that when the patient's symptom can't correspond with his or her diagnosis, we should ask more questions, evaluate the patient thoroughly and make the differential diagnosis as possible as we can. And the surgery can be performed aggressively when patient's symptoms cannot be figured out by physical examination, not only for pathologic confirmation but also for the prevention of life-threatening complications that can caused by either condition.

We present a case of a 47-year-old man who was admitted to the cardiac surgery department with a clinical picture of heart failure and multiple Tu-formations in three of the heart cavities. He underwent extraction of the tumor formations from the heart cavities with an excellent outcome.

Background: Postoperative cerebral infarction is a rare but serious complication after lung cancer surgery. We aimed to investigate the risk factors and evaluate the efficiency of our devised surgical procedure to prevent cerebral infarction. Methods: We retrospectively examined 1,189 patients who underwent a single lobectomy for lung cancer at our institution. We identified the risk factors for cerebral infarction and investigated the preventive effects of performing resection of the pulmonary vein as the last step of the surgical procedure during left upper lobectomy. Results: Among the 1,189 patients, we identified 5 male patients (0.4%) with postoperative cerebral infarction. All five underwent left-sided lobectomy including three upper and two lower lobectomies. Left-sided lobectomy, a lower forced expiratory volume in 1 s, and lower body mass index were associated with postoperative cerebral infarction (Ps < 0.05). The 274 patients who underwent left upper lobectomy were stratified by two procedures: lobectomy with resection of the pulmonary vein as the last step of the surgical procedure (n = 120) and the standard procedure (n = 154). The former procedure significantly shortened the length of the pulmonary vein stump when compared with the standard procedure (mean stump length: 15.1 vs. 18.6 mm, P < 0.01), and the shorter pulmonary vein might possibly prevent postoperative cerebral infarction (frequency: 0.8% vs. 1.3%, Odds ratio: 0.19, P = 0.31). Conclusions: Resecting the pulmonary vein as the last step during the left upper lobectomy enabled the length of the pulmonary stump to be significantly shorter, which may contribute to preventing cerebral infarction. [ABSTRACT FROM AUTHOR]

Thrombosis remains a leading cause of death worldwide despite technological advances in prevention, diagnosis, and treatment. The traditional view of arterial thrombus formation is that it is a platelet‐dependent process, whereas that of venous thrombus formation is a coagulation‐dependent process. Current pathological and basic studies on atherothrombosis and venous thrombosis have revealed the diverse participation of platelet and coagulation activation mechanisms in both thrombus initiation and growth processes during clinical thrombotic events. Atherosclerotic plaque cell‐derived tissue factor contributes to fibrin formation and platelet aggregation. The degree of plaque disruption and a blood flow alteration promote atherothrombotic occlusion. While blood stasis/turbulent flow due to luminal stenosis itself initiates venous thrombus formation. The coagulation factor XI‐driven propagation phase of blood coagulation plays a major role in venous thrombus growth, but a minor role in hemostasis. These lines of evidence indicate that atherothrombosis onset is affected by the thrombogenic potential of atherosclerotic plaques, the plaque disruption size, and an alteration in blood flow. Upon onset of venous thrombosis, enhancement of the propagation phase of blood coagulation under blood stasis and a hypercoagulable state contribute to large thrombus formation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Thrombosis is a major cause of morbidity and mortality worldwide. Platelet activation by exposed collagen through glycoprotein VI (GPVI) and formation of neutrophil extracellular traps (NETs) are critical pathogenic factors for arterial and venous thrombosis. Both events are regulated by spleen tyrosine kinase (Syk)‐mediated signalling events. Asebogenin is a dihydrochalcone whose pharmacological effects remain largely unknown. This study aims to investigate the antithrombotic effects of asebogenin and the underlying molecular mechanisms. Experimental Approach: Platelet aggregation was assessed using an aggregometer. Platelet P‐selectin exposure, integrin activation and calcium mobilization were determined by flow cytometry. NETs formation was assessed by SYTOX Green staining and immunohistochemistry. Quantitative phosphoproteomics, microscale thermophoresis, in vitro kinase assay and molecular docking combined with dynamics simulation were performed to characterize the targets of asebogenin. The in vivo effects of asebogenin on arterial thrombosis were investigated using FeCl3‐induced and laser‐induced injury models, whereas those of venous thrombosis were induced by stenosis of the inferior vena cava. Key Results: Asebogenin inhibited a series of GPVI‐induced platelet responses and suppressed NETs formation induced by proinflammatory stimuli. Mechanistically, asebogenin directly interfered with the phosphorylation of Syk at Tyr525/526, which is important for its activation. Further, asebogenin suppressed arterial thrombosis demonstrated by decreased platelet accumulation and fibrin generation and attenuated venous thrombosis determined by reduced neutrophil accumulation and NETs formation, without increasing bleeding risk. Conclusion and Implications: Asebogenin exhibits potent antithrombotic effects by targeting Syk and is a potential lead compound for the development of efficient and safe antithrombotic agents. [ABSTRACT FROM AUTHOR]

Surface modification is believed to be one of the most effective solutions to prevent thrombus formation associated with mechanical heart valves. Herein, we report, for the first time, the fabrication of a gradient cobblestone pattern on the pyrolytic carbon (PyC) surface aiming to improve its anti-thrombotic properties. A unique cobblestone pattern with gradient changing interspacing was generated on the PyC surface through laser etching. After coating with fluorosilane, the surface exhibited a water contact angle gradient ranging from 110 to 173°. The morphological and physicochemical properties, mechanical durability, drag reduction, in vitro anti-thrombotic properties, and in vivo biocompatibility of the surface were investigated to evaluate its potential as a heart valve replacement. It was found that the hydrophobic gradient wettability surface exhibited an excellent self-driving effect and mechanical durability, significantly reduced hemolysis rate and platelet adhesion, and prolonged coagulation time compared to the counterpart without gradient wettability. Furthermore, the gradient wettability surface demonstrated excellent in vivo biocompatibility. These findings are important for the design of artificial heart valves with improved anti-thrombotic performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus. Methods: (1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA. Results: The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806–5.500; p < 0.001). Twenty-seven patients agreed to undergo TEE during follow-up, no clinical ischemic stroke events were recorded, no recurrent intracardiac thrombus formation was detected in patients, 15 patients maintained sinus rhythm (55.6%) during follow-up; successful CA significantly increased LAAFV (difference between latest evaluation prior to CA 17.46 ± 14.81 cm/s, p < 0.001). Conclusions: Persistent AF is the only independent risk factor for thrombus formation. Successful CA may improve the LAAFV and thereby decrease the risk of intracardiac thrombus formation. [ABSTRACT FROM AUTHOR]

In this study, we present a method to quantitatively analyze the thrombus formation process through image analysis in an in vitro thrombus model with a circular cross section. The thrombus model used was designed based on the mechanism between the physical principle of wall shear rate (WSR) and thrombus formation. Image analysis was used to help visualize the thrombus formation process and calculate the thrombus area. Through this method, the thrombus formation and growth from the channel wall was demonstrated without the use of fluorescence. In addition, by dividing the image into sub-sections, the accuracy of the thrombus growth pattern was improved. The departing blood clots which are called embolus, were observed being separated from the thrombus. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 and type 3 von Willebrand disease (VWD) are caused by partial and complete, quantitative deficiency of von Willebrand factor (VWF), respectively, and factor (F)VIII/VWF complex concentrates are used for haemostatic treatment. Emicizumab, mimics activated FVIII, reduces bleeding in haemophilia A patients. The effects of emicizumab on haemostasis in both types of VWD remain to be fully established, however. Aim: To examine the effects of emicizumab on thrombogenesis in type 1 and type 3 VWD. Patients/Methods: Perfusion chamber experiments under high shear conditions (2500 s–1) combined with immunostaining were performed using whole blood samples from patients with type 1 (VWF:Ag 25 U/dl) and type 3 VWD (<1.0 U/dl). Results: The addition of FVIII (1 U/ml) to type 1 blood did not affect thrombus formation, whilst supplementation with VWF (1.6 U/ml) or FVIII/VWF (1 U/ml/1.6 U/ml) enhanced thrombogenesis to a similar extent. FVIII/VWF promoted thrombus formation significantly more than VWF alone, however, in type 3 blood. Emicizumab (100 μg/ml) augmented thrombus formation in type 3 blood compared to FVIII, and this potency seemed to be somewhat greater than that of VWF. Surface coverage of formed thrombus in type 3 VWD was less than that in type 1 VWD, but thrombus height was comparable in both. The addition of emicizumab to type 3 blood enhanced thrombin generation and fibrin formation compared to control IgG. Conclusion: Emicizumab promoted mechanisms of thrombus formation in vitro in type 3 and type 1 VWD, suggesting the possibility of alternative therapeutic protocols in these patients. [ABSTRACT FROM AUTHOR]

Equine gastrointestinal tract is infected with Strongylus vulgaris (S. vulgaris) which is highly pathogenic parasite for its harmful effect on cranial mesenteric artery during its migration. So, this study was applied for identification of S. vulgaris in donkeys ultramorphologically and molecularly. In addition to, detection of the pathological effect of larval stage of S. vulgaris on the mesenteric arterial system using histopathology and immunohistochemistry. During the period from September to December; 2019, 60 male and 20 female donkeys at the Giza Zoo was postmortem examined. S. vulgaris adults and larvae were collected from the large intestine and cranial mesenteric arteries (CMAs), respectively. Ultramorphological examination of the collected adults was done using scanning electron microscope (SEM). DNA was extracted from 5 larvae and 6 adults for further conventional PCR studies and sequencing of the internal transcriped spacer 2 (ITS2) gene. The ITS2 gene were amplified and showed bands at 148 base pair (bp). The ITS2 gene nucleotide sequences of all isolates were aligned using Basic Local Alignment Search Tool (BLAST). Histological sections of S. vulgaris affected mesenteric arteries exhibited the presence of the parasite larvae either in the lumen with thrombus formation or attached to the intima. Most of the detected inflammatory cell populations were CD68-positive cells. From these results, it can be concluded that the ribosomal spacers genes could be used as markers for Strongylus species identification in eggs collected from equine feces as a beneficial method of diagnosis. Also, it could be important in disease surveillance, improving preventive measures and developing an effective control strategy. [ABSTRACT FROM AUTHOR]

Glycoprotein (GP)VI and integrin αIIbβ3 are key signaling receptors in collagen-dependent platelet aggregation and in arterial thrombus formation under shear. The multiple downstream signaling pathways are still poorly understood. Here, we focused on disclosing the integrin-dependent roles of focal adhesion kinase (protein tyrosine kinase 2, PTK2), the shear-dependent collagen receptor GPR56 (ADGRG1 gene), and calcium and integrin-binding protein 1 (CIB1). We designed and synthetized peptides that interfered with integrin αIIb binding (pCIB and pCIBm) or mimicked the activation of GPR56 (pGRP). The results show that the combination of pGRP with PTK2 inhibition or of pGRP with pCIB > pCIBm in additive ways suppressed collagen- and GPVI-dependent platelet activation, thrombus buildup, and contraction. Microscopic thrombus formation was assessed by eight parameters (with script descriptions enclosed). The suppressive rather than activating effects of pGRP were confined to blood flow at a high shear rate. Blockage of PTK2 or interference of CIB1 no more than slightly affected thrombus formation at a low shear rate. Peptides did not influence GPVI-induced aggregation and Ca2+ signaling in the absence of shear. Together, these data reveal a shear-dependent signaling axis of PTK2, integrin αIIbβ3, and CIB1 in collagen- and GPVI-dependent thrombus formation, which is modulated by GPR56 and exclusively at high shear. This work thereby supports the role of PTK2 in integrin αIIbβ3 activation and signaling. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a common cardiac arrhythmia characterized by irregular and rapid electrical activity in the atria, leading to ineffective contraction and poor blood flow. More than 90% of the left atrial (LA) thrombi that cause thromboembolic events during atrial fibrillation (AF) develop in the left atrial appendage (LAA). AF modifies the hemodynamics of the left atrium, which can result in thrombosis of the LAA, systemic embolism, and stroke. The current options to reduce thromboembolic events are oral anticoagulation, surgical LAA exclusion, or percutaneous LAA occlusion. However, the mechanism underlying thrombus development in the LAA remains poorly understood. Computational fluid dynamics (CFD) analysis can be used to better understand the risk of thrombus formation and subsequent embolic events. CFD enables the simulation and visualization of blood flow patterns within the heart, including complex structures such as the LAA. Using CFD, researchers can analyze the hemodynamics of blood flow, identify areas of stagnation or turbulence, and predict the risk of thrombus formation. The correlation between blood flow dynamics, atrial fibrillation, and the risk of stroke has been highlighted by CFD studies investigating the underlying mechanism of thrombus formation in the LAA. This review study intends to provide a comprehensive overview of the factors involved in thrombus formation and their implications for clinical practice by synthesizing the insights acquired from these CFD studies.

Alzheimer's disease (AD) is the most common form of dementia and characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tau tangles and neurodegeneration. Over 80 % of AD patients also exhibit cerebral amyloid angiopathy (CAA). CAA is a cerebrovascular disease caused by deposition of Aβ in the walls of cerebral blood vessels leading to vessel damage and impairment of normal blood flow. To date, different studies suggest that platelet function, including activation, adhesion and aggregation, is altered in AD due to vascular Aβ deposition. For example, the transgenic AD model mice APP23 mice that exhibit CAA and parenchymal Aβ plaques, show pre-activated platelets in the blood circulation and increased platelet integrin activation leading to a pro-thrombotic phenotype in these mice late stages of AD. However, it is still an open question whether or not platelets exhibit changes in their activation profile before they are exposed to vascular Aβ deposits. Therefore, the present study examined platelets from middle-aged transgenic APP23 mice at the age of 8–10 months. At this age, APP23 mice show amyloid plaques in the brain parenchyma but not in the vasculature. Our analyses show that these APP23 mice have unaltered platelet numbers and size, and unaltered surface expression of glycoproteins. However, the number of dense granules in transgenic platelets was increased while the release was unaltered. Male, but not female APP23 mice, exhibited reduced platelet activation after stimulation of the thrombin receptor PAR4 and decreased thrombus stability on collagen under flow conditions ex vivo compared to control mice. In an arterial thrombosis model in vivo , male APP23 mice showed attenuated occlusion of the injured artery compared to controls. These findings provide clear evidence for early changes in platelet activation and thrombus formation in male mice before development of overt CAA. Furthermore, reduced platelet activation and thrombus formation suggest sex-specific differences in platelet physiology in AD that has to be considered in future studies of platelets and their role in AD. [ABSTRACT FROM AUTHOR]

Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was shown that PANX1 channels modulate platelet functions. To date, it remains unclear how PANX1 channels are activated and which signaling mechanisms are responsible for impaired hemostasis and thrombosis. Analysis of PANX1 phosphorylation at Tyr198 and Tyr308, and the impact on platelet activation and thrombus formation using genetically modified platelets or pharmacological inhibitors. Platelet activation via immunoreceptor tyrosine-based activation motif (ITAM) coupled, G Protein-Coupled Receptors (GPCR) and thromboxane receptor (TP)-mediated signaling pathways led to increased PANX1 phosphorylation at Tyr198 and Tyr308. We identified the Src-GPVI signaling axes as the main pathway inducing PANX1 activation, while PKC and Akt play a minor role. PANX1 channels function as ATP release channels in platelets to support arterial thrombus formation. PANX1 activation is regulated by phosphorylation at Tyr198 and Tyr308 following platelet activation. These results suggest an important role of PANX1 in hemostasis and thrombosis by releasing extracellular ATP to support thrombus formation. [ABSTRACT FROM AUTHOR]