Thrombosis Formation Research Articles

In silico model to assess thrombosis risk of TAVR with hemodynamic predictors using fluid structure interaction

Abstract The promising results of transcatheter aortic valve replacement (TAVR) over the past two decades indicate an expansion of the patient cohort toward patients with intermediate or low surgical risk. Since some complications of TAVR have already been minimized, subclinical leaflet thrombosis (SLT) has gained importance in recent years. SLT is manifested by a thrombotic layer on the prosthetic leaflets that gradually reduces leaflet motion. The resulting decrease in functionality of the TAVR causes a need for re-intervention. The origin of SLT and approaches to prevent SLT are still unexplored. For this reason, we have developed an in silicomodel that can be used during the design development process of TAVR devices to estimate the thrombosis risk of the implant. Based on passive scalar transport, hemodynamic metrics are used to quantify platelet activation and aggregation which are associated with the formation of thrombosis. In conjunction with a numerical simulation model considering the fluid-structure interaction between the blood mimicking fluid and the TAVR implanted in an aortic root, the thrombosis risk can be modeled. The simulation model can be used to calculate the three-dimensional flow structures within the native sinus and neo-sinus and also provides the ability to derive metrics to assess the risk of thrombosis. We demonstrated that this in silicomodel is a time-effective tool to assess thrombosis risk in TAVR product development.

Intranasal Delivery of Endothelial Cell-Derived Extracellular Vesicles with Supramolecular Gel Attenuates Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury. We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan's Blue and Masson's staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis. The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced. We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.

Ex-vivo Mechanical Augmentation of Human Saphenous Vein Graft By UV-A Irradiation in Emergency Vascular Reconstruction – Preliminary Results

Abstract Introduction In vascular reconstruction in arterial trauma, ruptured abdominal aortic aneurysm or ruptured aneurysmal arteriovenous fistula, the challenge no longer lies in the surgical procedure itself, but rather the prevention of intimal hyperplasia, thrombosis and aneurysm formation, in parallel with extending as long as possible the patency of the grafts. The aim of this study is to present the preliminary findings of a novel non-ionizing radiation-based therapeutic method for stabilizing and strengthening the extracellular matrix of the venous wall, improving the biomechanical profile of the autologous graft used in myocardial and lower limb revascularization. Material and methods We developed the protocol and method for UV-A irradiation as a new method of mechanical augmentation of the resistance structure of the venous graft. Samples of the superficial femoral artery, superficial femoral vein, and great saphenous vein (GSV) were extracted from a 58-year-old patient who underwent above-the-knee amputation, and were prepared in 5 × 5 cm2 patches. Additionally, we analyzed the samples biomechanically biaxially with the BioTester® 5000, in which we established a 25% equibiaxial stretch. The GSV sample was also treated by UV-A irradiation after being kept in riboflavin 5′-phosphate monosodium salt for 30 min. Results After UV-A treatment of the GSV wall, we observed an important increase of Cauchy stress from 82 kPa to 131 kPa in the longitudinal axis and from 66 kPa to 115 kPa in the circumferential axis. Young’s modulus also changed after treating the GSV wall from 0.564 MPa to 1.218 MPa (longitudinal) and from 0.397 MPa to 0.709 MPa (circumferential). As a result of the therapy, we observed a considerable similarity of the mechanical behavior of the GSV wall to that of the artery wall. Conclusion The photocrosslinking of collagen fibbers at the vein graft adventitia hardens and stiffens the venous wall, making it behave like the arterial wall after treatment. These preliminary ex vivo results on human vascular tissue may serve as the foundation for the development of new treatment approaches utilizing mechanical augmentation of the vein grafts.

Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

Molecular dynamics simulation of force-regulated interaction between talin and Rap1b

The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.

“Hooking method” for hepatic inflow control: a new approach for laparoscopic Pringle maneuver

BackgroundThe laparoscopic Pringle maneuver is crucial for controlling bleeding during laparoscopic hepatectomy. In this study, we introduce a new laparoscopic Pringle maneuver and preliminarily investigate its application in laparoscopic hepatectomy.MethodsWe collected and analyzed the clinical data of 17 consecutive patients who underwent laparoscopic hepatectomy at the Department of Hepatic Surgery, the First Affiliated Hospital of the University of Science and Technology of China, from January 2022 to January 2023. All patients underwent the hooking method for intermittent occlusion of hepatic inflow. Intraoperative and postoperative clinical indices were observed and recorded.ResultsAll 17 patients underwent laparoscopic hepatectomy with hepatic inflow control using the hooking method. Four patients with adhesions under the hepatoduodenal ligament successfully had occlusion loops placed using the hooking method combined with Zhang’s modified method during surgery. The median occlusion time for the 17 patients was 34 (12–60) min, and the mean operation time was 210 ± 70 min. The mean intraoperative blood loss was 145 ± 86 ml, and no patients required intraoperative blood transfusion. The patients’ postoperative peak AST was 336 ± 183 U/L, and the postoperative peak ALT was 289 ± 159 U/L. Postoperative complications occurred in 2 patients (11.8%), including 1 Clavien-Dindo grade I and 1 Clavien-Dindo grade II complication. No Clavien-Dindo grade IIIa or higher complications or deaths occurred in any patient. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. The median postoperative hospital stay was 6 (4–14) days.ConclusionThe hooking method combines the advantages of both intracorporeal Pringle maneuver and extracorporeal Pringle maneuver. It is a simple, safe, and effective method for controlling hepatic inflow and represents a promising approach for performing totally intracorporeal laparoscopic Pringle maneuver.

Rose Bengal induced formation of thrombosis in rats and an investigation of cardiovascular worries by haematological changes

BackgroundThe present investigation planned to study the cardiovascular worries in Rose Bengal (RB) induced thrombotic rats by analysing biochemical profile of plasma, platelet membrane and cardiac tissue. MethodsMale Wistar rats were categorized into two groups. The group I was Control (C) rats and received glucose, whereas group II was Rose Bengal (50 mg/kg) induced thrombotic rats. The animals sacrificed and biological samples collected were analysed for various biochemical parameters. ResultsIn rats RB induced heart damage/thrombosis showed significantly increased levels of lipid peroxidation (LPO), nitrate and nitrite. In RB administered group the antioxidant activities were lowered significantly i.e., reduced glutathione, glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase when compared with control rats. Plasma enzymes SGOT, SGPT were decreased and Na+-K+ ATPase was significantly increased in group II in comparison with group I. There is no significant change in plasma hexokinase enzyme in RB administered rats when compared with control rats. The non-enzymatic and enzymatic antioxidants levels were decreased significantly in experimental groups II to compare with control group I rats. A significant increase in platelet membrane fluidity observed in group II rats when compared with group I rats in DPH and pyrene employed method. A significant raise in LPO of platelet membrane was observed in the experimental rats. Plasma nitrite and nitrate levels were increased in group II when compared to group I. Furthermore, the haematological parameters were also increased in group II when compared to group I rats. ConclusionThis investigation pointed out that the nitric oxide scavenging levels increased and might be protected the oxidative stress and free radicals generated by RB induced cardiac thrombosis in rats.

Heparin Induced Thrombocytopenia - Pathophysiology, Diagnosis and Treatment: A Narrative Review.

Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated complication following heparin exposure and is considered to be the most severe adverse reaction to heparin treatment that is not associated with bleeding. Development of autoantibodies against platelet factor 4 (PF4) - heparin complex constitutes the basis of the pathophysiological changes in patients suffering from HIT, which then binds to the surface of platelets and monocytes, thus provoking their activation and subsequent aggregation, ultimately leading to the formation of thrombosis. Formation of arterial and venous thrombosis is aggravated by the simultaneous activation of platelets and monocytes with a substantial mortality rate. The incidence of HIT is reported to be significantly lower in pediatric patients compared with adults. Diagnosis of HIT in pediatric population remains a clinical entity supplemented by laboratory evaluation. The positive predictive value of laboratory evaluation is further elevated by the use of scoring systems and predictive models used for hastening the diagnosis of HIT. Use of alternative anticoagulants like direct thrombin inhibitors and factor Xa inhibitors form the mainstay of treatment in cases of HIT, however, more prospective studies would be required in the pediatric population to delineate definitive guidelines for proper management of patients in this age-group. This article delivers diagnostic and treatment approach in case of patients with HIT, wherein the pathophysiology, clinical manifestations, diagnostic approach and the management of patients with HIT has been described.

Computational analysis of thrombosis risk with variations in left ventricular assist device inflow cannula design in a multi-patient model

Background and ObjectivesLeft ventricular assist devices (LVADs) are mechanical pumps used to support patients with end-stage heart failure. The inflow cannula is a critical component of the LVAD as it connects the pump to the left ventricle, allowing blood to be drawn from the heart. However, the design of the cannula can significantly impact LV hemodynamics and cause complications, including thrombosis. Therefore, this study aimed to analyze the numerical effects of left ventricle (LV) size on cannula design in order to enhance hemodynamic performance using post-operative left ventricular assist device (LVAD) models. MethodsA parametric design evaluation of two different inflow cannulas were carried out on left ventricles (LV) of varying sizes (ranging from 154 to 430 ml) constructed from computerized tomography (CT) data from VAD patients using computational fluid dynamics (CFD) simulations. The study analyzed three key factors contributing to thrombosis formation: blood residence time, blood stagnation ratio, and wall shear stress. ResultsResults showed higher blood residence time and stagnation ratio for larger left ventricular sizes. In addition, increasing the insertion length of the cannula reduced the average wall shear stress. ConclusionOverall, the study's findings suggest that the optimal cannula shape for LVADs varies with left ventricular size.

Understanding the formation of spontaneous thrombosis inside aneurysms

Understanding the formation of spontaneous thrombosis inside aneurysms

Portal vein thrombosis: Before, during, and after liver transplant.

Portal vein thrombosis: Before, during, and after liver transplant.

Left lateral decubitus computed tomography before catheter ablation in patients with atrial fibrillation.

Aim The study aimed to determine the efficacy of cardiac computed tomography angiography (CCTA) for diagnosing left atrial appendage (LAA) thrombus before catheter ablation with the patient in the left lateral decubitus position and, also, to evaluate the risk factors for thrombus formation.Material and methods This retrospective, cohort study included 101 patients with atrial fibrillation. All patients underwent transthoracic echocardiography (TTE) and left lateral decubitus CCTA. Transesophageal echocardiography (TEE) was performed to confirm or exclude LAA thrombus. Patients with allergic reactions to iodinated contrast media, increased serum creatinine, hyperthyroidism, pregnancy, and age<18 years were excluded. The CHA2‑DS2‑VASc and HAS-BLED scores were calculated for each patient.Results All LAA thrombi detected on CCTA were confirmed by TEE. Higher CHA2‑DS2‑VASc, HAS-BLED scores, enlarged LA, and the anteroposterior dimension of the left atrium were significantly associated with the presence of LAA thrombus. A LAA cauliflower shape was a predictor of thrombus. An increase of LAA volume by 1 ml increased the chances of LAA thrombus and cerebral ischemic infarct by 2 %. The growth of the LAA anteroposterior diameter by 1 cm increased the risk of LAA thrombus by 190 % and of cerebral infarct by 78 %. An increase in the CHA2DS2‑VASc score by 1 point increased the risk of thromboembolism and cerebral infarction by 12 %.Conclusions CCTA performed in the left lateral decubitus position of the patient is an optimal screening tool to detect or exclude LAA thrombus before catheter ablation because of atrial fibrillation. CCTA has predictive value for risk of thrombosis formation in LAA.

Deep vein thrombosis - the role of ultrasound in the diagnosis and follow-up of patients.

Deep vein thrombosis still represents a challenge regarding the diagnostics, treatment and follow-up. All this steps are often performed in the internal medicine ambulatory centers and such clinics therefore need to be aable to manage the whole process. Its key part is vascular sonography, which is needed to establish the diagnosis, the form of thrombosis and proper treatment course. There are two types of vascular sonography - Point of Care a expert sonography, being performed in two different regimes (diagnostic and follow up sonography). There are different demands for each of these two types, and each type is performed by physicians with different level of expertise. There are well defined criteria for performance a conclusions made for each type, and their precise fulfillment leads to establishment of diagnosis of DVT, early treatment initiation and setting of optimal strategy following the baseline treatment period.

Association between higher systemic immune inflammation index (SII) and deep vein thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment.

Inflammation contributes to deep vein thrombosis (DVT) formation in patients with aSAH after endovascular treatment. The relationship between systemic immune-inflammatory index (SII) as an inflammatory marker and DVT formation remains unclear. Thus, this study aims to evaluate the association between SII and aSAH-associated DVT following endovascular treatment. We enrolled 562 consecutive patients with aSAH after endovascular treatment at three centers from January 2019 to September 2021. The endovascular treatments included simple coil embolization and stent-assisted coil embolization. Deep venous thrombosis (DVT) was assessed by Color Doppler ultrasonography (CDUS). Multivariate logistic regression analysis was used to establish the model. We assessed the association of the SII, neutrophil-to-lymphocyte ratio (NLR), the systemic inflammatory response index (SIRI), platelet-lymphocyte ratio (PLR), and DVT by using restricted cubic spline (RCS). ASAH-associated DVT was found in 136 (24.20%) patients. Based on the multiple logistic regression analysis, the correlation was found between aSAH-associated DVT and elevated SII (fourth quartile) (adjusted odds ratio = 8.20 [95% confidence interval, 3.76-17.92]; p < 0.001 [p for trend < 0.001]), elevated NLR (fourth quartile) (adjusted odds ratio = 6.94 [95% confidence interval, 3.24-14.89]; p < 0.001 [p for trend < 0.001]), elevated SIRI (fourth quartile) (adjusted odds ratio = 4.82 [95% confidence interval, 2.36-9.84]; p < 0.001 [p for trend < 0.001]), and elevated PLR (fourth quartile) (adjusted odds ratio = 5.49 [95% confidence interval, 2.61-11.57]; p < 0.001 [p for trend < 0.001]). The increased SII was correlated with the formation of aSAH-associated DVT after endovascular treatment.

Shear‐Responsive Drug Delivery Systems in Medical Devices: Focus on Thrombosis and Bleeding

AbstractCardiovascular disease is the leading cause of death worldwide. Blood‐contacting medical devices provide critical support for patients with severe respiratory and/or cardiac failure. High shear stress zones and non‐biocompatible circuit can increase the risk of thrombus formation in patients. These thrombi restrict blood flow through the circuits and travel to the lungs and brain, creating significant consequences. Antithrombotic drugs are used to lower this risk, but they also raise the incidence of bleeding problems. This article explores the delicate balance between thrombosis and bleeding in medical devices by examining platelet activation and thrombosis formation under shear stress. The feasibility of a shear‐responsive nanomedicine‐based drug delivery system has been explored as a potential approach for targeted administration of antithrombotic medications to lower systemic drug levels and reduce the bleeding risk. Furthermore, the lack of in vitro platforms to investigate the biological behavior of antithrombotic nanoparticles is impeding their clinical translation. As a result, microfluidic technology offers a platform for investigating nanoparticle behavior in vitro and linking it to their performance in vivo. Finally, the challenges and factors that affect the functionality, stability, and circulation time of liposomal drugs are investigated to improve their efficacy for targeted drug administration in medical devices.

Vasotoxic Effects of Anticancer Therapy: a Review of Current Data

Cardiovascular and oncological diseases are the leading causes of adult death in the world. Despite proven efficacy, anticancer drugs can cause severe cardiovascular complications. Recently, data have appeared on the possible vasotoxic effects of chemotherapy drugs, which can manifest themselves as the progression of arterial hypertension and atherosclerosis, the development of myocardial ischemia and acute coronary syndrome, the formation of venous and arterial thrombosis. The key mechanism for the development of vasotoxicity is endothelial dysfunction, and anticancer drugs can also affect the processes of thrombosis. The review presents the results of 12 selected observational retro- and prospective studies involving cancer patients receiving presumably vasotoxic therapy. Data on the frequency of occurrence and possibilities for the prevention of vasotoxicity are presented.

The WATCHMAN Device Review: A New Era for Stroke Prophylaxis.

Atrial fibrillation (AF) is a major risk factor for ischemic stroke, accounting for more than 37 million cases worldwide. In AF, the left atrial appendage (LAA) is the most common site of thrombus formation, and its ligation/closure with the WATCHMAN device is a good alternative to long-term oral anticoagulation, especially in patients with contraindications to warfarin. However, the implantation procedure is associated with various risks and complications. A short-term anticoagulant and antithrombotic administration are essential after implantation. However, no consensus has been reached on the optimal regimen. The WATCHMAN device is non-inferior to warfarin and is a safe alternative for the prevention of stroke and systemic embolization related to non-valvular atrial fibrillation (NVAF). Important procedure-related complications include pericardial effusion (PE), device embolization, procedure-related ischemic stroke, and device-related thrombosis (DRT) formation. It is essential to optimize post-implantation therapy according to individual patient bleeding risk, DRT formation, and contraindication to direct oral anticoagulants (DOACs). Recent studies have also shown that DOACs are a convenient and non-inferior substitute for warfarin. Furthermore, patients with absolute contraindications to OACs/DOACs can only be managed with dual antiplatelet therapy (DAPT). Transesophageal echocardiography (TEE) should be used to assess residual peridevice flow and possible DRT formation at days 45 and 12 months. Low molecular weight heparin (LMWH) and OAC are excellent choices for DRT treatment if detected. This review summarizes the most important complications of the WATCHMAN device in the existing literature and discusses various anticoagulation strategies and challenges post-implementation.

Effect of Vitamin E on Apoptosis of the Endothelial Cells of the Carotid Arteries in Hypercholesterolemic Male Rabbits.

Cardiovascular disease is the principal cause of mortality and morbidity in developed countries, leading to the formation of atherosclerosis plaques and thrombosis. Apoptosis of endothelial cells is one of the primary factors in vascular thrombosis. Lipids, when oxidized by endothelial cells, result in an increased thickness of the arterial wall. Iron is also recognized as an atherogenic element that induces atherosclerosis. There remains uncertainty about the antioxidative role of vitamin E in the formation of atherosclerosis. In this study, the authors evaluated the effect of iron and vitamin E on the apoptosis of endothelial cells in the carotid arteries of hypercholesterolemic male rabbits. Thirty white male rabbits were randomly divided into five groups and fed the following diet for six weeks: Group 1: control, Group 2: cholesterol (1%), Group 3: cholesterol (1%) + vitamin E (50 mg/kg), Group 4: cholesterol (1%) + Iron (50 mg/kg), and Group 5: cholesterol (1%) + vitamin E (50 mg/kg) + Iron (50 mg/kg). Serum cholesterol, TG, HDL, and LDL levels were assessed after six weeks. Finally, the animals were sacrificed with ketamine, and carotid arteries were removed. The samples were fixed in 10% formalin, and TUNEL staining was used after the tissue processing. Cell counts were carried out under a light microscope. Vitamin E decreased Serum cholesterol and apoptotic endothelial cells in the hypercholesterolemic + vitamin E diet (P< 0.05). However, they increased significantly in the interference groups compared to the control group (P< 0.05). According to our findings, vitamin E showed to have a beneficial effect on preventing cardiovascular diseases and may play a positive role in the prevention of atherosclerosis.

Wall shear gradient dependent thrombosis studied in blood-on-a-chip with stenotic, branched, and valvular constructions.

Thrombosis is the leading cause of death, while the effect of the shear flow on the formation of thrombus in vascular constructions has not been thoroughly understood, and one of the challenges is to observe the origination of thrombus with a controlled flow field. In this work, we use blood-on-a-chip technology to mimic the flow conditions in coronary artery stenosis, neonatal aortic arch, and deep venous valve. The flow field is measured by the microparticle image velocimeter (μPIV). In the experiment, we find that the thrombus often originates at the constructions of stenosis, bifurcation, and the entrance of valve, where the flow stream lines change suddenly, and the maximum wall shear rate gradient appears. Using the blood-on-a-chip technology, the effect of the wall shear rate gradients on the formation of the thrombus has been illustrated, and the blood-on-a-chip is demonstrated to be a perspective tool for further studies on the flow-induced formation of thrombosis.

Progress on the molecular mechanism of portal vein tumor thrombosis formation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with poor prognosis and high mortality. Early-stage HCC has no obvious clinical symptoms, and most patients are already at an advanced stage when they are diagnosed. Portal vein tumor thrombus (PVTT) is the most common complication and a poor prognostic factor for HCC, which frequently leads to portal vein hypertension, ascites, gastrointestinal bleeding, and tumor metastasis. The formation of PVTT is related to the complex structure and hemodynamic changes of the portal vein and is closely related to changes at the cellular and molecular levels. The differentially-expressed genes (DEGs) between PVTT and primary tumor (PT) suggest that the two tissues may have different clonal origins. Epigenetic and proteomic analyses also suggest complex and diverse mechanisms for the formation of PVTT. In addition, the tumor microenvironment and energy metabolism pathways are interrelated in regulating the invasion and progression of PVTT. Aerobic glycolysis and the tumor immune microenvironment have been the focus of recent studies on PVTT. In this review, we summarize the mechanism of PVTT formation at the cellular and molecular levels to provide information to guide better prevention and treatment of PVTT in the clinic.