Mechanism Of Thrombus Formation Research Articles

Predictive Methods for Thrombus Formation in the Treatment of Aortic Dissection and Cerebral Aneurysms: A Comprehensive Review.

Thrombus formation plays a crucial role in the clinical treatment of certain diseases. In conditions such as aortic dissection and cerebral aneurysm, complete thrombus occlusion in the affected region is desired to reduce blood flow into the false lumen or aneurysm sac, leading to a decrease in the tension exerted on the vascular wall and making it less likely to rupture. However, desired thrombosis sometimes fails to occur. Predicting thrombus formation can provide valuable information in such cases. This article offers a comprehensive review of conventional methods for predicting thrombus formation. In reviews conducted from the year 2000 to the present, the number of published related papers every five years has increased more than tenfold. We also found that the predictive methods can be classified into two categories: those based on the hemodynamic evaluation parameters and those based on hemodynamic and mathematical models that simulate the transport and reaction of blood components. Through our discussions, we identified several challenges that need to be resolved, including predictions based on patient-specific condition, model validation, multi-scale problems, the mechanisms of thrombus formation, and ensuring cost effectiveness. This review aims to guide researchers interested in exploring thrombus formation prediction within clinical treatments.

Modern concepts about the pathogenesis of thrombosis of various etiologies

Thrombosis becomes the cause and complication of many cardiovascular diseases, and their prevalence remains a leader in the structure of morbidity and mortality in Russia and throughout the world. Modern fundamental and clinical research has significantly supplemented traditional ideas about the mechanisms of thrombus formation. First of all, Virchow's triad has been rethought, in which, according to new data, the leading role is assigned to vascular damage, and slowing down blood flow plays a primary role in the formation of only venous, but not arterial, blood clots. In recent years, the mechanisms of endothelial dysfunction underlying thrombosis associated with inflammatory (immunothrombosis) and atherosclerotic (atherothrombosis) damage to the vascular wall have been studied in detail. The cellular and molecular mechanisms of acquired hypercoagulability and hereditary thrombophilia have been deciphered. The traditional concept of dividing blood clots into “red” (venous, consisting of fibrin and red blood cells) and “white” (arterial, platelet) is being revised. It has been shown that red blood cells can occupy most of the volume of not only venous, but also arterial thrombi, and play an important role in thrombus formation reactions. The process of compression (contraction, retraction) of blood clots, caused by contraction of activated platelets, changing the structure of the blood clot and affecting the course and outcome of thrombosis, is being actively studied. A deep understanding of the pathogenesis of thrombosis, taking into account modern concepts, is necessary for effective prevention, early diagnosis and treatment of thrombotic conditions.

A modern approach to the study of the problem of pathogenesis and prevention venous thromboembolic complications in patients with trauma (literature review)

Relevance. Patients with trauma are at increased risk of venous thromboembolic complications (VTE), which includes deep vein thrombosis of the lower extremities (DVT) and pulmonary embolism (PE). Within surgical and trauma clinics, thromboembolic complications are the most common preventable cause of in-hospital mortality. Numerous studies have shown that the incidence rate of deep vein thrombosis (DVT) in trauma patients without prevention varies from 5 to 80%.Aim. To analyze the pathogenesis of the development of venous thrombosis and explore existing approaches to prevent VTE in trauma patients.Materials and methods. In the course of the work, topical literary sources of domestic and foreign authors on a given topic were analyzed.Results. The mechanism of thrombus formation in trauma involves slowing blood flow, damage to the vessel wall and impaired blood clotting in the form of hypercoagulation. The state of hypercoagulation combined with prolonged immobility increases the risk of VTE. LMWH is the treatment of choice for the prevention of VTE in trauma. Today, there are ongoing studies related to the correction of preventive doses of LMWH and the search for a single standard, depending on numerous factors.Conclusion. Severity and multiplicity of lesions correlate with severity of systemic inflammation, hypercoagulation, and incidence of venous thrombosis. However, this correlation has not been sufficiently studied in the scientific literature. The search for specific methods for the prevention of deep vein thrombosis leading to PE is an urgent problem of surgery of injuries both peaceful and wartime.

MiRNAs and Their Role in Venous Thromboembolic Complications.

Venous thromboembolic complications (VTCs), which include deep vein thrombosis (DVT) and pulmonary embolism (PE), have remained a pressing problem in modern clinical medicine for a long time. Despite the already wide arsenal of modern methods for diagnosing and treating this disease, VTCs rank third in the structure of causes of death among all cardiovascular diseases, behind myocardial infarction (MI) and ischemic stroke (IS). Numerous studies have confirmed the importance of understanding the molecular processes of VTCs for effective therapy and diagnosis. Significant progress has been made in VTC research in recent years, where the relative contribution of microRNAs (miRNAs) in the mechanism of thrombus formation and their consideration as therapeutic targets have been well studied. In this case, accurate, timely, and as early as possible diagnosis of VTCs is of particular importance, which will help improve both short-term and long-term prognoses of patients. This case accounts for the already well-studied circulating miRNAs as non-invasive biomarkers. This study presents currently available literature data on the role of miRNAs in VTCs, revealing their potential as therapeutic targets and diagnostic and prognostic tools for this terrible disease.

A Case of an Unusual Clinical Course of Mitral Stenosis

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.

BIO22: Effects of Leakage Flows around TAVI models on Thrombus Formation by Optical Visualization Method with Various Geometries in Vitro

Background: There is a possibility of leakage (PVL; Paravalvular leak) flow around TAVI (Transcatheter Aortic Valve Implantation) and a high risk of thrombus formation. To find out the mechanism of thrombus formation by this leakage flow is important issue. In our previous studies, effects of the high shear rate on the thrombus formation rate at wall on orifice flow were examined by observation of thrombus formation using laser sheet, and it was found that the thrombus formation rates increase with the high shear rates. In this study, observation of thrombus formation around TAVI models including leakage flows by laser sheet in vitro with various geometries. Method: Experimental objects are orifice pipe flow and the leakage models with (Fig.1) for observation of thrombus formation. Each leakage size h is 0mm, 0.5mm, 1mm respectively with 20 mm diameter with stenosis to simulate valve part. The target flow filed with fresh blood plasma of pigs is observed with high speed CCD camera by laser sheet. Once the thrombus formation starts, the scattering wave can be detected by this system. The movies for three kinds of geometries and two flow rates (3 and 5l/min). Results & Conclusions: As for visualization results, typical distribution of thrombus formation area at h= 0, 0.5, 1 mm is shown in Fig.2. Due to the increasing of leakage size, the thrombus formation area at the outer wall decreases. In case of leakage size h=0.5 and 1 mm, these areas correspond to wake size at the back side of the stenosis. Figure 3 shows the thrombus formation rate by evaluation of the thrombus area with changing the leakage size and geometries. It was found that the thrombus formation rate increases with the leakage size, and there are differences between the two geometries. These findings related thrombus formation area were also evaluated from the leakage flow rates in the CFD (Computational Fluid Dynamics) results. And it was also found that this formation rates increase with leakage flow rate obtained by CFD. In conclusion, there is a high possibility to generate thrombus formation with larger leakage flow for TAVI. In future, the effects of valve motion should be investigated.

Sinus hemodynamics after transcatheter aortic valve implantation: Effect of native leaflet length and aortic sinus diameter

There are several methods for treating aortic stenosis including transcatheter valve implantation (TAVI) and surgical aortic valve replacement. Among these, TAVI is highly recommended for elderly patients with high surgical risk or a life expectancy of less than 10 yr. However, recent research findings indicate that thrombosis after TAVI leads to the malfunction of TAVI leaflets, which increases the risk of stroke and heart attack. Since the mechanism of thrombus formation is unclear, this study aimed to investigate the sinus hemodynamics after TAVI in different configurations using particle image velocimetry. The results showed that compared with SAV, the TAV resulted in a relatively low velocity at the sinus owing to the native leaflet and skirt of the TAV. The native leaflet length, covering over 75% of TAV, significantly increased the flow stasis and particle residence. In addition, a larger sinus diameter corresponded to a larger stasis area of the same length as that of the native leaflet. According to this study, patients with long native leaflets in their aortic sinus are at a higher risk of developing thrombosis and may require a higher deployment during treatment.

An autopsy case of cerebral arterial thrombosis after vaccination with ChAdOx1 nCOV-19

We present a fatal case of cerebral arterial thrombosis after corona virus disease 19 (COVID-19) vaccination with ChAdOx1 nCOV-19. The deceased was a 63-year-old woman with no relevant medical history. She presented symptoms of nausea, fatigue, and headache immediately after vaccination. Ten days after vaccination, she suddenly started vomiting and developed high blood pressure. The patient eventually died 23 days after vaccination. Autopsy findings showed that the cerebral arteries and internal carotid arteries were fully enlarged and were compacted with thrombi. The brain stem showed ischemic necrosis, and extravasation from this necrotic lesion led to focal subarachnoid hemorrhage around the brain stem where large blood clots still remained. No aneurysms or atherosclerotic changes were found in these arteries. We note the following three facts. Firstly, all symptoms occurred immediately after vaccination; secondly, the main cause of death was consistent with known side effects of the vaccine; and lastly, the mechanism of thrombus formation in this case goes beyond the general category of thrombogenesis known so far. While the authors know that this case does not fall into known categories of vaccine side effects, we presenting this case to demonstrate that a comprehensive review of various possibilities related to vaccine side effects is needed to establish a COVID-19 defense system.

アテローム血栓症における血栓形成機序

心筋梗塞や脳梗塞に代表されるアテローム血栓症の多くは，動脈硬化性プラークの破綻による血栓形成によって発症する．筆者らは病理学の立場から，アテローム血栓症の発症機序の解明に取り組んできた．プラーク破綻部の血栓は，健常動脈と異なり，血小板に加えて多量のフィブリンから成る．これはプラーク内のマクロファージや平滑筋細胞が，動脈硬化の進行に伴い組織因子を高発現するためで，プラークの組織性状や破綻の様式（破裂，びらん）によって血小板とフィブリンの度合いが異なることを見出した．これらの所見を踏まえて，ヒトの病態を反映しうるアテローム血栓症の動物モデルを作成した．プラーク内の組織因子は，CRPをはじめ多くの炎症関連因子やプラーク内出血などに起因する酸化ストレスによって誘導される．加えてプラーク内の低酸素環境も組織因子を強く誘導すること，これに対する細胞内代謝変化が血栓形成能と関連することも明らかにした．また組織因子は，VII因子とプロテアーゼ活性化受容体を介して平滑筋細胞の遊走など，凝固反応以外の生理作用も有し，プラーク形成の促進にも寄与することを見出した．血小板の活性化では，進行した動脈硬化巣ではecto-NTPDase/CD39が減少し，CLEC-2の生体内リガンドであるポドプラニンの発現による活性化亢進が認められる．一方，プラーク破綻は無症候性（血栓が小さく非閉塞性）のものが多いことから，破綻部における血栓の増大機序に着目し，血栓の増大には，プラーク自体の血栓形成能と破綻の程度に加えて，血流の状態，内因系凝固反応，VWF/ADAMTS13などが寄与することを示した．またXI因子は，その活性阻害により，出血時間の延長なく血栓の増大を抑制することを見出し，新たな抗血栓薬のターゲットとなることを報告した．

Postprocedural Thrombosis following Endovascular Treatment of Intracranial Aneurysm with Flow Diverters or Coiling: A Histologic Study.

Endovascular treatment of aneurysms with flow diverters or coiling is sometimes complicated by intraprocedural or postprocedural thrombosis along or within the devices. Thrombus composition and structure associated with such complications may provide insights into mechanisms of thrombus formation and clinical strategies to remove the thrombus. We present a retrospective histopathologic study of 4 patients who underwent mechanical thrombectomy due to acute occlusion of either implanted flow diverter devices or along coils during the treatment of intracranial aneurysm.

Vulnerable atherosclerotic plaque features: findings from coronary imaging.

Pathological studies have suggested that features of vulnerable atherosclerotic plaques likely to progress and lead to acute cardiovascular events have specific characteristics. Given the progress of intravascular coronary imaging technology, some large prospective studies have detected features of vulnerable atherosclerotic plaques using these imaging modalities. However, the rate of cardiovascular events, such as acute coronary syndrome, has been found to be considerably reduced in the limited follow-up period available in the statin era. Additionally, not all disrupted plaques lead to thrombus formation with clinical presentation. If sub-occlusive or occlusive thrombus formation does not occur, a thrombus on a disrupted plaque will organize without any symptoms, forming a “healed plaque”. Although vulnerable plaque detection using intracoronary imaging is focused on “thin-cap fibroatheroma” leading to plaque rupture, superficial plaque erosion is increasingly recognized; however, the underlying mechanism of thrombus formation on eroded plaques is not well understood. One of intravascular imaging, optical coherence tomography (OCT) has the highest image resolution and has enabled detailed characterization of the plaque in vivo. Here, we reviewed the status and limitations of intravascular imaging in terms of detecting vulnerable plaque through mainly OCT studies. We suggested that vulnerable plaque should be reconsidered in terms of eroded plaque and healed plaque and that both plaque and circulating blood should be assessed in greater detail accordingly.

Complement, inflammation and thrombosis.

A mutual relationship exists between immune activation and mechanisms of thrombus formation. In particular, elements of the innate immune response such as the complement system can modulate platelet activation and subsequently thrombus formation. Several components of the complement system including C3 or the membrane attack complex have been reported to be associated with platelets and become functionally active in the micromilieu of platelet activation. The exact mechanisms how this interplay is regulated and its consequences for tissue inflammation, damage or recovery remain to be defined. This review addresses the current state of knowledge on this topic and puts it into context with diseases featuring both thrombosis and complement activation. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.

The features of the thrombolytics use in the process of the reversal of acute coronary occlusion syndrome

The mechanism of thrombus formation is a coordinated process that is under the control of neurohumoral regulation and is influenced by a variety of external and internal factors. Any disruption in the regulatory system, activation of some factors and inhibition of others can lead to disruption in the coagulation system, affecting both the plasma and platelet links of hemostasis. The activation of platelets against the background of the existing atherosclerosis of the vessels leads to the formation of blood clots, which clog the lumen of the coronary vessels and can lead to acute myocardial infarction. Today it is well known that increased thrombus formation is not only the cause of the development of acute conditions, but also leads to the progression of the disease. The leading role in the initiation of the thrombus formation process is played by platelets, therefore, the use of antiplatelet drugs is an obligatory link in both the treatment and prevention of thrombosis. In this case, the most important is the need to restore blood flow in the coronary vessels, which provide nutrition to the myocardium. In this regard, correctly selected antithrombotic agents can take a worthy place in the treatment and prevention of cardiovascular pathology, which is based on ischemic thrombosis.

Сравнительное изучение кинетики свертывания крови и тромбообразования реологическими и электрореологическими методами.

Цель исследования: изучить механизмы формирования и тромбодинамические свойства кровяного сгустка при тромбообразовании in vitro и представить сравнительное исследование кинетики тромбообразования с помощью реологических и электрореологических методов в условиях постоянного и осциллирующего сдвигового вискозиметрического течения; оценить свертывание цельной и консервированной крови, ее вязкоупругие свой ства и влияние фибриногена и декстранов на формирование сгустка. Материалы и методы. Вязкость и удельную электропроводимость нормальной и консервированной с CPD-A1-адениновым раствором крови измеряли ротационным вискозиметром Low Shear 30 Contraves (LS30) с коаксиальными цилиндрами и копией измерительной системы MS1/1 со встроенными электродами (разработана на базе LS30) в условиях постоянного сдвигового потока и в электрическом поле. Вязкоупругие свойства нормальной цельной крови исследовали с помощью реометра Physica MCR 301 (Anton Paar, Austria) в условиях осциллирующего синусоидального потока. Результаты. Представлены результаты кинетики динамической вязкости и удельной электропроводимости консервированной крови в процессе коагуляции в условиях постоянного сдвигового потока и в электрическом поле. Исследованы вязкоупругие свойства цельной крови в условиях синусоидального осциллирующего вискозиметрического течения и представлены зависимости упругого модуля G' (storage modulus) и модуля потерь G'' (loss modulus), а также нормальных сил как функция времени при свертывании. Приводятся данные эффекта фибриногена и декстрана на упругий модуль G' и на модуль потерь G'' цельной крови в процессе коагуляции. Заключение. В условиях вискозиметрического течения при низких скоростях сдвига кинетика тромбообразования характеризуется начальным этапом постепенного увеличения кажущейся вязкости и уменьшения удельной электропроводимости крови и периодом интенсивной коагуляции, характеризирующимся экспоненциальным ростом вязкости и параллельным уменьшением удельной электропроводимости исследуемого образца. Установлено, что коагулирующая цельная кровь обладает нелинейными вязкоупругими свойствами. Кинетика образования сгустка в условиях осциллирующего вискозиметрического течения крови характеризуется увеличением упругого модуля G' и модуля потерь G'' со временем. Одновременно зарегистрирована и отрицательная нормальная сила исследуемого образца в зазоре между пластинами при постоянной толщине зазора. Повышение содержание фибриногена ускоряет коагуляцию и увеличивает значения упругого модуля G' и модуля потерь G'', а также и нормальной силы коагулирующей цельной крови. Objectives: to study the mechanisms of thrombus formation and thrombodynamic properties of a blood clot during coagulation in vitro and to present a comparative study of clot kinetics formation under conditions of steady and oscillating shear viscometric flow and at electric field by rheological and electrorheological methods; to evaluate the coagulation of whole and preserved blood, its viscoelastic properties and the effect of fi brinogen and dextrans on clot formation. Materials/ Methods. The viscosity and electrical conductivity of normal blood and blood preserved with CPD-A1-adenine solution were measured with a Low Shear 30 Contraves (LS30) rotational viscometer with coaxial cylinders and with a copy of the measuring system MS1 / 1 with builtin electrodes at a steady viscometric shear flow and in an electric field too. The viscoelastic properties of normal whole blood were investigated using a Physica MCR 301 rheometer (Anton Paar, Austria) at an oscillating sinusoidal flow. Results. Kinetics of the dynamic viscosity and electrical conductivity of preserved blood during coagulation at a steady shear flow and at electric field were obtained. The viscoelastic properties of whole blood were investigated under conditions of sinusoidal oscillating viscometric flow. The dependences of the elastic (storage) modulus G' and the loss modulus G'', as well as the normal coagulation forces as a function of time are presented. The effect of fibrinogen and dextran on the elastic modulus G' and the loss modulus G'' of whole blood during coagulation are presented. Conclusions. The kinetics of blood coagulation at low shear rates is characterized by a gradual increase of the apparent viscosity and a decrease in blood conductivity at the initial stage and an exponential increase in viscosity during intensive coagulation and a parallel decrease of conductivity too. It was established that coagulating whole blood exhibit nonlinear viscoelastic properties under conditions of sinusoidal blood flow. The kinetics of thrombus formation is characterized by increasing the elastic modulus G' (storage modulus) and the loss modulus G'' with time. The negative normal force in the gap between the plates is also registered at a constant thickness of the gap. An increase in fibrinogen content accelerates coagulation and increases the values of elastic modulus G' and loss modulus G', as well as of the normal force of coagulating whole blood.

Super-Resolution Microscopy Reveals an Altered Fibrin Network in Cirrhosis: The Key Role of Oxidative Stress in Fibrinogen Structural Modifications.

Cirrhotic patients show a reduced synthesis of both pro- and anti-coagulant factors. Recent reports indicate that they are characterized by a higher risk of thrombotic rather than hemorrhagic complications, but the mechanisms conferring this risk are not fully elucidated. Oxidative-mediated fibrinogen modifications may explain, at least in part, a prothrombotic profile. The aim of the present pilot study was to investigate the alterations in fibrinogen structure and function in patients with cirrhosis of various severity and to correlate these findings with the mechanisms of thrombus formation. We assessed in plasma specific oxidative stress markers and measured oxidative modifications, functional and structural parameters in purified fibrinogen fractions obtained from cirrhotic patients and control subjects. We enrolled 15 cirrhotic patients (5 patients belonging to each of the three Child–Turcotte–Pugh classes) and 20 age- and sex-matched healthy controls. Plasma redox status, fibrinogen oxidative modifications, thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in cirrhotic patients and were associated to disease severity. Importantly, clot structure obtained by stimulated emission depletion (STED) super-resolution microscopy indicated modifications in fiber diameter and in clot porosity in cirrhotic patients. Fibrin fiber diameter significantly decreased in cirrhotic patients when compared to controls, and this difference became more marked with disease progression. In parallel, fibrin pore size progressively decreased along with disease severity. In cirrhotic patients, fibrinogen clot analysis and oxidative-dependent changes reveal novel structural and functional fibrinogen modifications which may favor thrombotic complications in cirrhosis.

Pathogenic Mechanisms of Venous Thromboembolism in Ovarian Tumor Patients

Venous thromboembolism (VTE) is a serious complication of ovarian cancer. However, the mechanism of thrombus formation in ovarian cancer has not been sufficiently clarified. We aimed to examine the pathogenic mechanism of thromboembolism in patients with ovarian tumors before surgery using the activated protein C sensitive ratio (APC-sr) and endogenous thrombin potential (ETP) measurements in plasma. The incidence of thromboembolism in patients with ovarian tumors was determined. APC-sr and ETP were measured from plasma samples obtained from ovarian tumor patients before surgery at our hospital. There were 60 enrolled patients. Thrombosis was found in 10 patients, of which 9 had ovarian cancer and 1 had borderline malignancy. The incidence of thromboembolism was significantly higher in cases of ovarian cancer than in cases of benign and borderline tumors (p < 0.001). However, APC-sr and ETP did not differ between patients with and without thromboembolism (p = 0.681, 0.796). APC-sr and ETP may not be involved in the pathogenic mechanism of thromboembolism in patients with ovarian tumors before surgery. Thus, other approaches should be considered for detecting the pathogenic mechanism of thromboembolism in this population.

Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques.

Atherothrombosis is a leading cause of cardiovascular mortality and morbidity worldwide. The underlying mechanisms of atherothrombosis comprise plaque disruption and subsequent thrombus formation. Arterial thrombi are thought to mainly comprise aggregated platelets as a result of high blood velocity. However, thrombi that develop on disrupted plaques comprise not only aggregated platelets, but also large amounts of fibrin, because plaques contain large amount of tissue factor that activate the coagulation cascade. Since not all thrombi grow large enough to occlude the vascular lumen, the propagation of thrombi is also critical in the onset of adverse vascular events. Various factors such as vascular wall thrombogenicity, local hemorheology, systemic thrombogenicity and fibrinolytic activity modulate thrombus formation and propagation. Although the activation mechanisms of platelets and the coagulation cascade have been intensively investigated, the underlying mechanisms of occlusive thrombus formation on disrupted plaques remain obscure. Pathological findings derived from humans and animal models of human atherothrombosis have uncovered pathophysiological processes during thrombus formation and propagation after plaque disruption, and novel factors have been identified that modulate the activation of platelets and the coagulation cascade. These findings have also provided insights into the development of novel drugs for atherothrombosis.

Downstream platelet adhesion and activation under highly elevated upstream shear forces

Elevated shear force caused by an anastomotic stenosis is a common complication at the blood vessel-vascular implant interface. Although elevated shear forces were found to cause platelet aggregation around a stenotic region, transient platelet exposure to elevated shear forces and subsequent downstream events occurring under lower shear force were not extensively studied. We hypothesize that effects of elevated shear forces on pre-activation of platelets for downstream adhesion and activation are relevant in understanding the increased thrombotic risk associated with blood-contacting devices. We designed a microfluidic flow system to mimic the hemodynamic environment of vasculature with an upstream anastomotic stenosis with five wall shear strain rates ranging from 1620 s−1 to 11560 s−1. Under shear flow conditions, transient exposure of whole blood to elevated shear forces resulted in higher downstream platelet adhesion onto three different immobilized platelet agonists: fibrinogen, collagen, or von Willebrand factor. Platelet expression of four activation markers (P-selectin, GPIIb/IIIa, lysosomal glycoprotein, and phosphatidylserine) significantly increased after transient exposure to higher upstream wall shear strain rates of 2975–11560 s−1. A significant lysis was observed when platelets were primed by upstream wall shear strain rate of 11560 s−1. These experimental results could be helpful to understand how altered hemodynamics around an anastomotic stenosis promotes thrombus formation downstream. Statement of SignificanceStudying the downstream response of platelets following transient exposure to an upstream agonist is important because of significant clinical implications to the implantation of vascular devices. Due to intimal fibrous hyperplasia, vascular biomaterials such as synthetic small-diameter vascular grafts sometimes become stenotic (narrow), leading to transient platelet exposure to elevated shear forces. In this study, a microfluidic flow system was developed to mimic a stenosed vascular graft and to investigate how highly elevated, transient upstream shear forces, typically found in severe stenosis, results in the pre-activation of platelets for downstream adhesion and activation. The findings of the present study have implications for optimizing the design of blood-contacting biomaterials in order to minimize thrombotic risk associated with transiently elevated shear forces. The findings also provide additional insights into the mechanisms of thrombus formation at the post-stenotic regions of vascular implants.

Cerebral Thromboembolism after Lobectomy for Lung Cancer: Pathological Diagnosis and Mechanism of Thrombus Formation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although molecular therapies have emerged as efficacious strategies for the treatment of lung cancer, surgical resection is still recommended as a radical therapeutic option. Currently, lobectomy is regarded as the most reliable radical treatment of primary lung cancer. Among the various complications after lobectomy, cerebral thromboembolism requires attention as a life-threatening complication during the early postoperative period. It occurs in 0.2–1.2% of surgical cases of lung cancer and typically develops following left upper lobectomy with a long pulmonary vein stump (PVS). PVS-associated thrombosis is known to cause cerebral thromboembolism after such procedures; however, distinguishing this specific complication from that caused by postoperative atrial fibrillation is challenging. We summarize herein the diagnostic pathology of thrombus formation in accordance with its thrombogenic mechanism. We focus on the potential utility of the pathological assessment of thrombectomy specimens. The morphological information obtained from these specimens enables the presumption of thrombogenic etiology and provides useful clues to both select an appropriate pharmacotherapy and determine a follow-up treatment for cerebral thromboembolism.

Hemodynamic Characteristics in Aorta-Pulmonary Artery System

The child patients of hypoplastic left heart syndrome undergoes major operations such as the Norwood procedure, the Bidirectional Glenn procedure and the Fontan procedure. Patent Ductus Arteriosus (PDA) stenting, which is instead of these procedures, is recently performed to prevent closure of ductus arteriosus and to alleviate the burden for the patient. This study clarified that hemodynamics in aorta-pulmonary artery system and mechanism of thrombus formation using Computational Fluid Dynamics (CFD) analysis and Particle Imaging Velocimetry (PIV) measurement. As a result of CFD analysis, low wall shear stress was observed at neighborhood of PDA stent. From results of CFD analysis and PIV measurement, the main blood flow was formed toward from aorta to pulmonary artery and there is no blood stagnation region in PDA.