Treatment Of Thrombosis Research Articles

Direct oral anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study.

Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking. DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting. DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT. ClinicalTrials.gov, NCT04660747.

Treatment strategies for hepatic artery complications after pediatric liver transplantation: A systematic review.

This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure.

Direct oral anticoagulants for the treatment of splanchnic vein thrombosis: A state of art.

Splanchnic vein thrombosis (SVT) is a manifestation of venous thromboembolism in an unusual site. Portal, mesenteric, and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis, although non-cirrhotic patients could be affected as well. Thrombosis of hepatic veins, also known as Budd-Chiari syndrome, is another manifestation of SVT. Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications. Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases. However, recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants (DOACs) in this setting. Available results are mainly based on retrospective studies with small sample size, but first clinical trials have been published in the last years. This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients.

Current Status of and Barriers to the Implementation of Enhanced Recovery After Surgery in 77 Tertiary Hospitals

To investigate the status of and obstacles to the implementation of enhanced recovery after surgery (ERAS) in tertiary-care general hospitals in China. Questionnaire on the Current Status of and Barriers to the Implementation of ERAS in Tertiary-Care Hospitals, a self-developed questionnaire, was used to conduct a survey of 77 tertiary hospitals from 21 provinces across China between May 2022 and June 2022. The participating hospitals were selected by convenience sampling. The questionnaire on the current implementation status of ERAS was mainly focused on the departments involved and the ERAS programs implemented, incorporating a total of 25 items of three dimensions, preoperative, intraoperative, and postoperative. The answer to each question consisted of 5 options from "never" to "always", which corresponded to 1 to 5 points on the scoring scale, with the higher scores indicating better implementation of the program concerned. In the questionnaire on barriers to ERAS implementation and recommendations, 10 items of two dimensions, including hospital management, and patient and caregiver, were concerned with the barriers to implementation. The answer to each question consisted of 5 options from "disagree" to "strongly agree", which corresponded to 1 to 5 points on the scoring scale, with the higher scores indicating the greater importance of the barriers. ERAS programs were implemented in 73 (94.8%) hospitals. The best-implemented items were preoperative education (4.73±0.51), prevention and treatment of deep vein thrombosis (4.55±0.71), and postoperative follow-up (4.40±0.81). The items of poor implementation status were preoperative prehabilitation (2.71±1.40), preoperative oral carbohydrate drinks (3.03±1.49), and early ambulation after surgeries (3.04±1.22). The main obstacles to ERAS implementation included a lack of effective incentive systems, poor motivation among the medical and nursing staffs (3.21±0.93), a lack of disease-specific clinical implementation pathways (3.16±1.06), and a lack of experience in multidisciplinary teamwork (2.98±1.17). There is a high rate of ERAS implementation in tertiary general hospitals in China, but clinical implementation and dissemination are still confronted with many obstacles.

Comparison of prevention and treatment of portal vein thrombosis between proximal splenic vein ligation followed by postoperative transcatheter anticoagulant therapy and systemic anticoagulant therapy in patients with cirrhotic portal hypertension

AbstractAimsSplenectomy combined with pericardial devascularization is one of the important methods to treat hypersplenism, gastrointestinal bleeding, and other complications caused by liver cirrhosis; however, it is accompanied by a high risk of portal vein thrombosis (PVT). This study aimed to explore the preventive and therapeutic effects of proximal splenic vein ligation (PSVL) with postoperative transcatheter anticoagulant therapy (TCAT) on PVT.MethodsThis study retrospectively selected 143 patients with liver cirrhosis and portal hypertension, who received splenectomy combined with pericardial devascularization from June 30, 2018 to June 30, 2021. According to computed tomography photography, within 1 week before the operation, the patients were divided into a prevention group (without preoperative PVT, n = 112) and a treatment group (preoperative PVT, n = 31). Then, each group was subdivided based on the treatment and prevention measures into PSVL + TCAT (n = 70) and systemic anticoagulant therapy (SAT) subgroups (n = 73). The preventive and therapeutic effects of PSVL followed by TCAT on PVT were analyzed.ResultsThe operation time in the PSVL + TCAT subgroups was longer than that in the SAT subgroups (185 ± 76 min vs. 161 ± 55 min; p < 0.01). There was no difference between the two subgroups in terms of operative bleeding (345 ± 82 mL vs. 336 ± 65 mL; p > 0.50). There was no operative death, and all patients recovered uneventfully. In the prevention group, procedure‐related complications occurred in two patients in the PSVL + TCAT subgroup (3.7% [2/54]), including one patient with slight pancreatitis and one patient with chylous leakage, owing to mobilization of the pancreas. The PVT incidence in the prevention group was significantly different between the two subgroups at postoperative 7th day, 3rd month, and 6th month (PSVL + TCAT: 0%, 11.1%, and 5.6% vs. SAT: 39.7%, 31.0%, and 20.7%, respectively; all p < 0.05). In the treatment group, the thrombus regression rate at postoperative 7th day and disappearance rates at the 3rd month and the 6th month of the PSVL + TCAT subgroup were significantly higher than those in the SAT subgroup after anticoagulant and thrombolysis therapy (PSVL + TCAT: 75.0%, 68.8%, and 87.5% vs. SAT: 20.0%, 26.7%, and 40.0%; all p < 0.05).ConclusionsPSVL + TCAT reduces the risk of PVT after splenectomy and is safe and effective in treating PVT during surgery for portal hypertension.

Comparison of Medical Treatment Efficiency With Shear Wave Elastography Values of Thrombus in Patients With Lower Extremity Deep Vein Thrombosis.

In lower-extremity deep vein thrombosis (DVT), thrombus age is essential for successful treatment. The aim of our study was to compare the shear wave elastography (SWE) values measured before treatment and achieved lumen patency after treatment in lower-extremity DVT patients with total occlusion. Patients diagnosed with DVT in the acute-subacute stage (<4 week) with total thrombosis in lower extremity were included in this prospective study. Shear wave elastography measurements were performed where the thrombus was most prominent and homogeneous. To evaluate patient response to treatment, lumen patency (partial [>25%] or total recanalization) was examined using color Doppler imaging in the first and third months posttreatment. Shear wave elastography values with and without patency were compared using an independent t test. Among 75 patients in this study, at the first-month color Doppler imaging examination, the SWE values were 1.77 ± 0.49 (1.09-3.03) m/s in patients who achieved lumen patency (n = 42) and 2.21 ± 0.54 (1.24-3.36) m/s in those who did not show lumen patency (n = 33). The difference between the groups' mean elastography value was statistically significant ( P < 0.001). At the third-month examination, the SWE values were 1.76 ± 0.46 (1.09-3.03) m/s in patients with lumen patency (n = 55) and 2.52 ± 0.48 (1.74-3.36) in patients without lumen patency (n = 20). The difference between the 2 groups' mean elastography value was statistically significant ( P < 0.001). We concluded that it is more difficult to achieve lumen patency in veins occluded by thrombus with higher elasto values, and endovascular interventional procedures should be considered during the initial treatment of high SWE value thrombosis.

MSOR4 Presentation Time: 5:00 PM: Stent Placement Plus Radioactive Seeds Implantation for the Treatment of Portal Vein Tumor Thrombosis

MSOR4 Presentation Time: 5:00 PM: Stent Placement Plus Radioactive Seeds Implantation for the Treatment of Portal Vein Tumor Thrombosis

Application of artificial neural network in daily prediction of bleeding in ICU patients treated with anti-thrombotic therapy

ObjectivesAnti-thrombotic therapy is the basis of thrombosis prevention and treatment. Bleeding is the main adverse event of anti-thrombosis. Existing laboratory indicators cannot accurately reflect the real-time coagulation function. It is necessary to develop tools to dynamically evaluate the risk and benefits of anti-thrombosis to prescribe accurate anti-thrombotic therapy.MethodsThe prediction model,daily prediction of bleeding risk in ICU patients treated with anti-thrombotic therapy, was built using deep learning algorithm recurrent neural networks, and the model results and performance were compared with clinicians.ResultsThere was no significant statistical discrepancy in the baseline. ROC curves of the four models in the validation and test set were drawn, respectively. One-layer GRU of the validation set had a larger AUC (0.9462; 95%CI, 0.9147–0.9778). Analysis was conducted in the test set, and the ROC curve showed the superiority of two layers LSTM over one-layer GRU, while the former AUC was 0.8391(95%CI, 0.7786–0.8997). One-layer GRU in the test set possessed a better specificity (sensitivity 0.5942; specificity 0.9300). The Fleiss’ k of junior clinicians, senior clinicians, and machine learning classifiers is 0.0984, 0.4562, and 0.8012, respectively.ConclusionsRecurrent neural networks were first applied for daily prediction of bleeding risk in ICU patients treated with anti-thrombotic therapy. Deep learning classifiers are more reliable and consistent than human classifiers. The machine learning classifier suggested strong reliability. The deep learning algorithm significantly outperformed human classifiers in prediction time.

Safety and efficacy of interventional treatment of acute limb ischemia in Germany 2021

PurposeInterventional procedures have become a mainstay in the therapy of acute limb ischemia caused by embolism or arterial thrombosis. Treatment options include pharmacological thrombolysis (PT) and mechanical thrombectomy (MT). The aim of this study was to evaluate success and major complication rates of interventional radiological treatments of arterial embolism and thrombosis in Germany in 2021 and to compare their results with accepted international quality standards.Materials and methodsData for PT and MT for 2021 was obtained from the quality management system of the German interventional radiological society (DeGIR). 2431 PT and 1582 MT procedures were documented for 2021, with 459 combinations of PT and MT. Data was analysed for technical and clinical success rates, as well as major complication rates such as intracranial bleeding, major bleeding, distal embolization, aneurysm formation, organ-failure and cardiac-decompensation.ResultsPT alone had technical and clinical success rate of 90.21% and 81.08%, respectively. MT alone had technical and clinical success rates of 97.41% and 95.39%, respectively. MT&PT had technical and clinical success rates of 91.07% and 84.75%, respectively. Major complications were: distal embolization (PT:2.02%; MT:1.74%; PT&MT:2.61%), major bleeding (PT:0.94%; MT:1.14%; PT&MT:0.87%), aneurysm formation (PT:0.33%;MT: 1.14%;PT&MT: 0%), intracranial bleeding (PT:0.16%;MT:0%;PT&MT:0.22%), cardiac-decompensation (PT:0.21%;MT: 0.06%;PT&MT:0%) and organ-failure (PT:0%;MT:0.06%;PT&MT:0.22%).Technical and clinical success rates were higher, while complication rates were lower than the corresponding threshold recommended by the Society of Interventional Radiology for percutaneous management of acute lower-extremity ischemia.ConclusionTreatment of arterial embolism and thrombosis performed by interventional radiologists in Germany is effective and safe with outcomes exceeding internationally accepted standards.

Rivaroxaban versus Low Molecular Weight Heparin in Treatment of Acute Deep Vein Thrombosis

Abstract Objectives The purpose of this study is to examine the use of low molecular weight heparin, warfarin, and rivaroxban in the treatment of acute deep vein thrombosis. Background A blood clot stops the passage of blood via vein, usually in the legs, causing deep vein thrombosis (DVT). Clots can detach and obstruct blood flow to the pulmonary, which can be deadly (pulmonary embolism (PE). Methodology This prospective study included 250 Patients with acute deep vein thrombosis 20 patients died (9 died due to Pulmonary embolism 1 died due to bleeding – 10 died due to myocardial infarction, stroke and cardiac aresst) during study, 30 patients lack of follow up. 100 Patients are subjected to low molecular weight heparin followed by warfarin and the other 100 subjected to rivaroxban. During the period of the study from Mars 2017 to July 2019 at emergency department in Menofia university. Results The total number of Patient selected for the tests was 200 Patient. The main age was 39 and the Minimum of age was 20 year and the maximum age are 55 year. the disruption of sex are not show any concentration in any groups, the mean BMI in Warfarin Group and Rivaroxban Group are the same with no significant, the age groups shows no statistically significant of data. Conclusion According to this study Warfarin need long term monitoring, Rivaroxaban does not require laboratory surveillance, which makes treatment easier, and there are no medication or dietary interactions with Rivaroxaban.

Comparative outcomes of catheter-directed thrombolysis versus AngioJet pharmacomechanical catheter-directed thrombolysis for treatment of acute iliofemoral deep vein thrombosis

ObjectiveThe objective of this study was to compare the outcomes of pharmacomechanical thrombolysis and thrombectomy (PCDT) plus catheter-directed thrombolysis (CDT) vs CDT alone for the treatment of acute iliofemoral deep vein thrombosis (DVT) and summarize the clinical experience, safety outcomes, and short- and long-term efficacy. MethodsWe performed a 4-year retrospective, case-control study. A total of 95 consecutive patients with acute symptomatic iliofemoral deep vein thrombosis (DVT) with a symptom duration of ≤7 days involving the iliac and/or common femoral veins underwent endovascular interventions. The patients were divided into two groups according to their clinical indications: PCDT plus CDT vs CDT alone. Statistical analyses were used to compare the clinical characteristics and outcomes between the two groups. Additionally, the patients were followed up for 3 to 36 months after treatment, and the proportions of post-thrombotic syndrome (PTS) and moderate to severe PTS were analyzed using the Kaplan-Meier survival method. ResultsA total of 95 consecutive patients were analyzed in this retrospective study, of whom, 51 underwent CDT alone and 44 underwent PCDT plus CDT. Between the two groups, in terms of immediate-term efficacy and safety, significant differences were found in the catheter retention time (60.64 ± 12.04 hours vs 19.42 ± 4.04 hours; P < .001), dosages of urokinase required (5.82 ± 0.81 million units vs 1.80 ± 0.64 million units; P < .001), the detumescence rate at 24 hours postoperatively (48.46% ± 8.62% vs 76.79% ± 7.98%; P = .026), the descent velocity of D-dimer per day (2266.28 ± 1358.26 μg/L/D vs 3842.34 ± 2048.02 μg/L/D; P = .018), total hospitalization stay (6.2 ± 1.40 days vs 3.8 ± 0.70 days; P = .024), number of postoperative angiograms (2.4 ± 0.80 vs 1.2 ± 0.30; P = .042), and grade III venous patency (>95% lysis: 54.5% vs 68.6%; P = .047). Furthermore, during the follow-up period, significant differences were found in the incidence of PTS (Villalta scale ≥5 or a venous ulcer: 47.0% vs 27.7%; P = .037), and the incidence proportion of moderate to severe PTS at 12 months (15.7% vs 4.5%; P = .024) and 24 months (35.3% vs 11.4%; P = .016). ConclusionsCompared with CDT alone, in the iliofemoral DVT subgroup with a symptom duration of ≤7 days, PCDT plus CDT could significantly relieve early leg symptoms, shorten the hospitalization stay, reduce bleeding complications, promote long-term venous patency, and decrease the occurrence of PTS and the incidence proportion of moderate to severe PTS. Thus, the short- and long-term outcomes both support the superiority of PCDT plus CDT vs CDT in this subgroup.

Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy.

Deep venous thrombosis (DVT) is a part of venous thromboembolism (VTE) that clinically manifests as swelling and pain in the lower limbs. The most serious clinical complication of DVT is pulmonary embolism (PE), which has a high mortality rate. To date, its underlying mechanisms are not fully understood, and patients usually present with clinical symptoms only after the formation of the thrombus. Thus, it is essential to understand the underlying mechanisms of deep vein thrombosis for an early diagnosis and treatment of DVT. In recent years, many studies have concluded that Neutrophil Extracellular Traps (NETs) are closely associated with DVT. These are released by neutrophils and, in addition to trapping pathogens, can mediate the formation of deep vein thrombi, thereby blocking blood vessels and leading to the development of disease. Therefore, this paper describes the occurrence and development of NETs and discusses the mechanism of action of NETs on deep vein thrombosis. It aims to provide a direction for improved diagnosis and treatment of deep vein thrombosis in the near future.

Antiphospholipid Syndrome: Thrombotic and Vascular Complications.

Antiphospholipid syndrome is a rare, autoimmune thrombophilia defined by vascular thrombosis and pregnancy morbidity, in the setting of documented persistent antiphospholipid antibodies including the lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I antibodies. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome, which involves widespread coagulopathy over a very short period of time. The degree of risk associated with antiphospholipid syndrome depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. The current standard treatment for unprovoked thrombosis is long-term warfarin. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin in pregnant patients. The use of direct oral anticoagulants in patients with antiphospholipid syndrome is still being debated. Their use is generally contraindicated, especially in high-risk patients, such as those with all 3 antiphospholipid antibodies present, but they may potentially be of some use in some low-risk patients.

A clinical case of successful treatment of coronary artery dissection and left ventricular thrombosis in a young man carrier of factor V Leiden gene and transient ischemic attack

One of the causes of transient ischemic attack or ischemic stroke are mass formations in the left heart. One of the predisposing factors for thrombosis is the presence of the Leiden mutation, as the most common form of hereditary thrombophilia in the European population. At the same time, spontaneous dissection of the coronary arteries (SCA) can be one of the reasons of an acute vascular accident. Of particular difficulty is differential diagnosis, which requires additional examination methods (intravascular ultrasound, optical coherence tomography) in addition to coronary angiography. The presented clinical case describes the diagnosis and successful treatment of spontaneous anterior interventricular artery dissection, left ventricular thrombosis, detection of factor V Leiden gene mutation in a young man with a history of transient ischemic attack

Six-Month Outcomes of Mechanical Thrombectomy for Treating Deep Vein Thrombosis: Analysis from the 500-Patient CLOUT Registry.

Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein. The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality of life scores through 6months were analyzed. Adverse events were identified and independently adjudicated. All-cause mortality at 30days was 0.9%, and 8.6% of subjects experienced a serious adverse event (SAE) within the first 30days, 1 of which (0.2%) was device related. SAE rethrombosis/residual thrombus incidence was 4.8% at 30days and 8.0% at 6months. Between baseline and 6months, venous flow increased from 27.2% to 92.5% of limbs (P < 0.0001), and venous compressibility improved from 28.0% to 91.8% (P < 0.0001), while median Villalta scores improved from 9.0 at baseline to 1.0 at 6months (P < 0.0001). Significant improvements in venous symptom severity, pain, and quality of life were also demonstrated. Outcomes from iliofemoral and isolated femoral-popliteal segments showed similar improvements. Outcomes from the CLOUT study, a large prospective registry for DVT, indicate that mechanical thrombectomy is safe and demonstrates significant improvement in symptoms and health status through 6months. Level of Evidence 3: Non-randomized controlled cohort/follow-up study.

Combined Computer-Aided Predictors to Improve the Thermostability of Nattokinase.

Food-derived nattokinase has strong thrombolytic activity and few side effects. In the field of medicine, nattokinase has been developed as an adjuvant drug for the treatment of thrombosis, and nattokinase-rich beverages and health foods have also shown great potential in the field of food development. At present, the poor thermostability of nattokinase limits its industrial production and application. In this study, we used several thermostability-prediction algorithms to predict nattokinase from Bacillus mojavensis LY-06 (AprY), and screened two variants S33T and T174V with increased thermostability and fibrinolytic activity. The t1/2 of S33T and T174V were 8.87-fold and 2.51-fold those of the wild type AprY, respectively, and their enzyme activities were also increased (1.17-fold and 1.28-fold, respectively). Although the thermostability of N218L was increased by 2.7 times, the fibrinolytic activity of N218L was only 73.3% of that of wild type AprY. The multiple-point mutation results showed that S33T-N218L and S33T-T174V-N218L variants lost their activity, and the T174V-N218L variant did not show any significant change in catalytic performance, while S33T-T174V increased its thermostability and activity by 21.3% and 24.8%, respectively. Although the S33T-T174V variant did not show the additive effect of thermostability, it combined the excellent transient thermostability of S33T with the better thrombolytic activity of T174V. Bioinformatics analysis showed that the overall structure of S33T and T174V variants tended to be stable, while the structure of S33T-T174V variant was more flexible. Local structure analysis showed that the increased rigidity of the active center region (positions 64-75) and the key loop region (positions 129-130, 155-163, 187-192, 237-241, and 268-270) determined the increased thermostability of all variants. In addition, the enhanced flexibility of S33T-T174V variant in the Ca1 binding region (positions 1-4, 75-82) and the peripheral region of the catalytic pocket (positions 210-216) may account for the inability to superpose its thermostability. We explored the effective strategy to enhance the thermostability of nattokinase, and the resulting variants have potential industrial production and application.

In silico evaluation of pharmacokinetic parameters, delivery, distribution and anticoagulative effects of new 4,7-dihydroxycoumarin derivative

In this study, pharmacological profiling and investigation of the anticoagulant activity of the newly synthesized coumarin derivative: (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (L) were performed. The obtained results were compared with the parameters obtained for Warfarin (WF), which is a standard good oral anticoagulant. The estimated high binding affinity of L toward plasma proteins (PPS% value is > 90%) justifies the investigation of binding affinity and comparative analysis of L and WF to Human Serum Albumin (HSA) using the spectrofluorimetric method (296, 303 and 310 K) as well as molecular docking and molecular dynamics simulations. Compound L shows a very good binding affinity especially to the active site of WF (the active site I -subdomain IIA), quenching HSA fluorescence by a static process. Also, the finite element smeared model (Kojic Transport Model, KTM), which includes blood vessels and tissue, was implemented to compute the convective-diffusion transport of L and WF within the liver. Finally, compound L shows a high degree of inhibitory activity toward the VKOR receptor comparable to the inhibitory activity of WF. Stabilization and limited flexibility of amino acid residues in the active site of the VKOR after binding of L and WF indicates a very good inhibitory potential of compound L. The high affinity of the L for the VKOR enzyme (Vitamin K antagonist), as well as the structural similarity to commercial anticoagulants (WF), provide a basis for further studies and potential application in the treatment of venous thrombosis, pulmonary embolism and ischemic heart disease. Communicated by Ramaswamy H. Sarma

Miniaturized Stacked Transducer for Intravascular Sonothrombolysis With Internal-Illumination Photoacoustic Imaging Guidance and Clot Characterization.

Thromboembolism in blood vessels can lead to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis enhanced by ultrasound contrast agents has shown promising outcome on effective treatment of thromboembolism. Intravascular sonothrombolysis was also reported recently with a potential for effective and safe treatment of deep thrombosis. Despite the promising treatment results, the treatment efficiency for clinical application may not be optimized due to the lack of imaging guidance and clot characterization during the thrombolysis procedure. In this paper, a miniaturized transducer was designed to have an 8-layer PZT-5A stacked with an aperture size of 1.4 × 1.4 mm2 and assembled in a customized two-lumen 10-Fr catheter for intravascular sonothrombolysis. The treatment process was monitored with internal-illumination photoacoustic tomography (II-PAT), a hybrid imaging modality that combines the rich contrast of optical absorption and the deep penetration of ultrasound detection. With intravascular light delivery using a thin optical fiber integrated with the intravascular catheter, II-PAT overcomes the penetration depth limited by strong optical attenuation of tissue. In-vitro PAT-guided sonothrombolysis experiments were carried out with synthetic blood clots embedded in tissue phantom. Clot position, shape, stiffness, and oxygenation level can be estimated by II-PAT at clinically relevant depth of ten centimeters. Our findings have demonstrated the feasibility of the proposed PAT-guided intravascular sonothrombolysis with real-time feedback during the treatment process.

Direct oral anticoagulants in the treatment of portal vein thrombosis in patients with portal hypertension.

Direct oral anticoagulants in the treatment of portal vein thrombosis in patients with portal hypertension.

Asundexian: an oral small moleculefactor XIa inhibitor for the treatment of thrombotic disorders.

Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding often dictate treatment decisions. Inhibition of the intrinsic coagulation system via factor XIa may allow for selective inhibition of the coagulation cascade without significantly impacting hemostasis after injury. Asundexian is an oral small moleculefactor XIa inhibitor that, via this novel mechanism, may prove to be a safe and effective option compared with available anticoagulants. Early clinical data forasundexian was promising as a safer alternative to current therapiesand prompted further analysis incertainpatient populations atincreasedthrombotic risk. Currently, studies areongoing to evaluate thesafety and efficacy in stroke prevention in atrial fibrillation and in patients following an acute noncardioembolic ischemic stroke or high-risk transient ischemic attack.