[New anticoagulants in 2024: Development of factor XI and XIa inhibitors]. / Les nouveaux anticoagulants en 2024 : développement des inhibiteurs du facteur XI et du XIa.

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible. New anticoagulants targeting the contact phase of coagulation are currently being developed and could make it possible to prevent the risk of thrombosis without impairing hemostasis. Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs). MATERIALS AND METHODS: A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients. Of these, 11,891 received antiplatelet-based treatment, and 11,524 received placebo/other drugs. Statistical analysis was performed using Review Manager 5.4. RESULTS: The included trials involved patients with a mean age ranging from 54.3 to 62.0 years and a prevalence of hypertension ranging from 10.9 to 65.0% and coronary artery disease ranging from 3.2 to 32.7%. The pooled analysis showed no significant difference in overall mortality between groups (RR 1.0, 95% CI 0.99 - 1.01, p = 0.76). However, antiplatelet therapy significantly reduced major thrombotic events (RR 0.86, 95% CI 0.75 - 0.99, p = 0.04). Conversely, it increased major bleeding risks (RR 1.62, 95% CI 1.24 - 2.12, p = 0.0005). There was no significant difference in the incidence of invasive mechanical ventilation and respiratory death. CONCLUSION: Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.

Nutrition and Cardiovascular Disease: The Potential Role of Marine Bioactive Proteins and Peptides in Thrombosis Prevention.

Thrombus and cardiovascular diseases pose a significant health threat, and dietary interventions have shown promising potential in reducing the incidence of these diseases. Marine bioactive proteins and peptides have been extensively studied for their antithrombotic properties. They can inhibit platelet activation and aggregation by binding to key receptors on the platelet surface. Additionally, they can competitively anchor to critical enzyme sites, leading to the inhibition of coagulation factors. Marine microorganisms also offer alternative sources for the development of novel fibrinolytic proteins, which can help dissolve blood clots. The advancements in technologies, such as targeted hydrolysis, specific purification, and encapsulation, have provided a solid foundation for the industrialization of bioactive peptides. These techniques enable precise control over the production and delivery of bioactive peptides, enhancing their efficacy and safety. However, it is important to note that further research and clinical studies are needed to fully understand the mechanisms of action and therapeutic potential of marine bioactive proteins and peptides in mitigating thrombotic events. The challenges and future application perspectives of these bioactive peptides also need to be explored.

[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

In situ formed depot of elastin-like polypeptide-hirudin fusion protein for long-acting antithrombotic therapy.

Thrombosis, induced by abnormal coagulation or fibrinolytic systems, is the most common pathology associated with many life-threatening cardio-cerebrovascular diseases. However, first-line anticoagulant drugs suffer from rapid drug elimination and risk of hemorrhagic complications. Here, we developed an in situ formed depot of elastin-like polypeptide (ELP)-hirudin fusion protein with a prodrug-like feature for long-term antithrombotic therapy. Highly secretory expression of the fusion protein was achieved with the assistance of the Ffu312 tag. Integration of hirudin, ELP, and responsive moiety can customize fusion proteins with properties of adjustable in vivo retention and controllable recovery of drug bioactivity. After subcutaneous injection, the fusion protein can form a reservoir through temperature-induced coacervation of ELP and slowly diffuse into the blood circulation. The biological activity of hirudin is shielded due to the N-terminal modification, while the activated key proteases upon thrombus occurrence trigger the cleavage of fusion protein together with the release of hirudin, which has antithrombotic activity to counteract thrombosis. We substantiated that the optimized fusion protein produced long-term antithrombotic effects without the risk of bleeding in multiple animal thrombosis models.

Overcoming barriers for left atrial appendage thrombus: a systematic review of left atrial appendage closure.

BACKGROUND: Approximately 90% of intracardial thrombi originate from the left atrial appendage in non-valvular atrial fibrillation patients. Even with anticoagulant therapy, left atrial appendage thrombus (LAAT) still occurs in 8% of patients. While left atrial appendage closure (LAAC) could be a promising alternative, the current consensus considers LAAT a contraindication to LAAC. However, the feasibility and safety of LAAC in patients with LAAT have yet to be determined. METHODS: This systematic review synthesizes published data to explore the feasibility and safety of LAAC for patients with LAAT. RESULTS: This study included a total of 136 patients with LAATs who underwent successful LAAC. The Amulet Amplatzer device was the most frequently utilized device (48.5%). Among these patients, 77 (56.6%) had absolute contraindications to anticoagulation therapy. Cerebral protection devices were utilized by 47 patients (34.6%). Transesophageal echocardiography (TEE) is the primary imaging technique used during the procedure. Warfarin and novel oral anticoagulants were the main anticoagulant medications used prior to the procedure, while dual antiplatelet therapy was primarily used post-procedure. During a mean follow-up period of 13.2 ± 11.5 months, there was 1 case of fatality, 1 case of stroke, 3 major bleeding events, 3 instances of device-related thrombus, and 8 cases of peri-device leakage. CONCLUSIONS: This review highlights the preliminary effectiveness and safety of the LAAC procedure in patients with persistent LAAT. Future large-scale RCTs with varied LAAT characteristics and LAAC device types are essential for evidence-based decision-making in clinical practice.

The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Bioinspired superhydrophobic surfaces with silver and nitric oxide-releasing capabilities to prevent device-associated infections and thrombosis.

Bacteria-associated infections and thrombus formation are the two major complications plaguing the application of blood-contacting medical devices. Therefore, functionalized surfaces and drug delivery for passive and active antifouling strategies have been employed. Herein, we report the novel integration of bio-inspired superhydrophobicity with nitric oxide release to obtain a functional polymeric material with anti-thrombogenic and antimicrobial characteristics. The nitric oxide release acts as an antimicrobial agent and platelet inhibitor, while the superhydrophobic components prevent non-specific biofouling. Widely used medical-grade silicone rubber (SR) substrates that are known to be susceptible to biofilm and thrombus formation were dip-coated with fluorinated silicon dioxide (SiO2) and silver (Ag) nanoparticles (NPs) using an adhesive polymer as a binder. Thereafter, the resulting superhydrophobic (SH) SR substrates were impregnated with S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) to obtain a superhydrophobic, Ag-bound, NO-releasing (SH-SiAgNO) surface. The SH-SiAgNO surfaces had the lowest amount of viable adhered E. coli (> 99.9 % reduction), S. aureus (> 99.8 % reduction), and platelets (> 96.1 % reduction) as compared to controls while demonstrating no cytotoxic effects on fibroblast cells. Thus, this innovative approach is the first to combine SNAP with an antifouling SH polymer surface that possesses the immense potential to minimize medical device-associated complications without using conventional systemic anticoagulation and antibiotic treatments.

Atrial Thrombosis Prevalence Before Cardioversion or Catheter Ablation of Atrial Fibrillation: An Updated Systematic Review and Meta-Analysis of Direct Oral Anticoagulants Versus Vitamin K Antagonists.

Left atrial or left atrial appendage thrombosis (LAT) is contraindicated for cardiac ablation (CA) or cardioversion (CV) of atrial fibrillation (AF). This study was aimed to compare the frequency of LAT detected by transesophageal echocardiography (TEE) before CA or CV in patients with AF treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). We searched PubMed, Scopus, Web of Science, and Cochran Library databases from inception through July 13, 2023 to select studies reporting data on LAT identification before CA or CV using TEE in patients with AF treated with DOACs or VKAs. Pooled odds ratios (ORs) with 95% confidence interval were calculated with a random-effects model. Studies retrieved were 50 (38 observational), 29 on CA, 15 on CV, and 6 on both procedures (17,096 patients on DOACs and 13,666 on VKAs). The overall prevalence of LAT was smaller in DOACs than in VKAs, with an OR of 0.66 (0.52 to 0.84), confirmed at sensitivity analysis and in most subgroups. This finding was consistent for the 3 most reported DOACs: the pooled OR for LAT was 0.68 (0.50 to 0.90) in apixaban, 0.67 (0.51 to 0.88) in dabigatran, 0.61 (0.43 to 0.89) in rivaroxaban, and 1.10 (0.74 to 1.64) in edoxaban (not significant). In conclusion, in this large meta-analysis in patients with AF, the prevalence of LAT by TEE evaluation performed before CV or CA appears lower in those treated with DOACs than in those on VKAs. Additional research may help in better understanding differences between these classes of anticoagulant drugs in the setting of protection against AF-related left atrial thrombotic formation.

A microthrombus-driven fixed-point cleaved nanosystem for preventing post-thrombolysis recurrence via inhibiting ferroptosis.

Thrombus-induced cardiovascular diseases threaten human health. Current treatment strategies often rely on urokinase plasminogen activator (uPA) for its efficacy, yet it has such limiting factors as short half-life, lack of thrombus targeting, and systemic side effects leading to unintended bleeding. In addition, thrombolytic interventions can trigger inflammation-induced damage at thrombus sites, which affects endothelial function. To address these challenges, Fer-1/uPA@pep-CREKA-Lipo (Fu@pep-CLipo) has been developed. This system achieves precise and efficient thrombolysis while enhancing the thrombus microenvironment and mitigating ischemia-reperfusion injury, with exceptional thrombus targeting ability via the strong affinity of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide for fibrin. The Cys-Nle-TPRSFL-DSPE (pep) could respond to the thrombus microenvironment and fixed-point cleavage. The uPA component linked to the liposome surface is strategically cleaved upon exposure to abundant thrombin at thrombus sites. Importantly, the inclusion of Fer-1 within Fu@pep-CLipo contributes to reactive oxygen species (ROS) scavenging and significantly improves the thrombus microenvironment. This innovative approach not only achieves highly efficient and precise thrombolysis but also positively influences the expression of eNOS protein while suppressing inflammatory factors like TNF-α and IL-6. This dual action contributes to improved thrombus inflammatory microenvironment and mitigated ischemia-reperfusion injury.

Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: A case series.

A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

Thrombosis prophylaxis following trauma.

PURPOSE OF REVIEW: This review explores the persistent occurrence of venous thromboembolic events (VTE) in major trauma patients despite standard thrombosis prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). It investigates the inadequacies of standard pharmacologic prophylaxis and proposes alternative approaches not covered in current trauma guidelines. RECENT FINDINGS: Recent studies highlight the effectiveness of monitoring and adjusting subcutaneous LMWH doses based on anti-Xa levels for the purpose of reducing VTE in trauma patients. The need for dose adaptation arises due to factors like fluctuating organ function, varying antithrombin levels, interaction with plasma proteins, and altered bioavailability influenced by oedema or vasopressor use. Additionally, promising alternatives such as intravenous LMWH, UFH, and argatroban have shown success in intensive care settings. SUMMARY: The standard dosing of subcutaneous LMWH is often insufficient for effective thrombosis prophylaxis in trauma patients. A more personalised approach, adjusting doses based on specific effect levels like anti-Xa or choosing an alternative mode of anticoagulation, could reduce the risk of insufficient prophylaxis and subsequent VTE.

Discovery of Potent and Selective Quinoxaline-Based Protease-Activated Receptor 4 (PAR4) Antagonists for the Prevention of Arterial Thrombosis.

PAR4 is a promising antithrombotic target with potential for separation of efficacy from bleeding risk relative to current antiplatelet therapies. In an effort to discover a novel PAR4 antagonist chemotype, a quinoxaline-based HTS hit 3 with low µM potency was identified. Optimization of the HTS hit through the use of positional SAR scanning and the design of conformationally constrained cores led to the discovery of a quinoxaline-benzothiazole series as potent and selective PAR4 antagonists. The lead compound 48, possessing a 2 nM IC50 against PAR4 activation by γ-thrombin in platelet-rich plasma (PRP) and greater than 2500-fold selectivity versus PAR1, demonstrated robust antithrombotic efficacy and minimal bleeding in the cynomolgus monkey models.

Multi-Omics Approaches for Liver Reveal the Thromboprophylaxis Mechanism of Aspirin Eugenol Ester in Rat Thrombosis Model.

Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE had excellent thromboprophylaxis and inhibition of platelet aggregation. This study aimed to investigate the effect of AEE on the liver of thrombosed rats to reveal its mechanism of thromboprophylaxis. Therefore, a multi-omics approach was used to analyze the liver. Transcriptome results showed 132 differentially expressed genes (DEGs) in the AEE group compared to the model group. Proteome results showed that 159 differentially expressed proteins (DEPs) were identified in the AEE group compared to the model group. Six proteins including fibrinogen alpha chain (Fga), fibrinogen gamma chain (Fgg), fibrinogen beta chain (Fgb), orosomucoid 1 (Orm1), hemopexin (Hpx), and kininogen-2 (Kng2) were selected for parallel reaction monitoring (PRM) analysis. The results showed that the expression of all six proteins was upregulated in the model group compared with the control group. In turn, AEE reversed the upregulation trend of these proteins to some degree. Metabolome results showed that 17 metabolites were upregulated and 38 were downregulated in the model group compared to the control group. AEE could reverse the expression of these metabolites to some degree and make them back to normal levels. The metabolites were mainly involved in metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. Comprehensive analyses showed that AEE could prevent thrombosis by inhibiting platelet activation, decreasing inflammation, and regulating amino acid and energy metabolism. In conclusion, AEE can have a positive effect on thrombosis-related diseases.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study.

OBJECTIVE: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. METHODS: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. RESULTS: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. CONCLUSION: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Unfractionated heparin: optimizing laboratory monitoring and reducing unwanted interference in everyday hemostasis test practice.

Unfractionated heparin (UFH) serves as a commonly used anticoagulant. It is widely utilized for a variety of reasons, including to 1) anticoagulate patients and help treat and / or prevent thrombosis, 2) maintain patency in artificial blood flow circuits, and 3) anticoagulate blood samples collected for laboratory testing (typically for biochemical assays or blood gas analysis). As such, the presence of UFH is nearly ubiquitous in a hospital setting. Therefore, in laboratory practice, UFH may be present in samples intended for monitoring patients on UFH therapy or intended for biochemical tests, or it may interfere with other (hemostasis) laboratory tests. The aim of this manuscript is to review the role of UFH from the perspective of optimizing laboratory testing to monitor UFH therapy and to avoid or overcome unwanted interference with other laboratory tests.

Prophylactic Anticoagulation to Prevent Left Ventricular Thrombus Following Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

Clinical practice guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent left ventricular thrombus (LVT) formation in patients with anterior ST-elevation myocardial infarction. These guidelines were given a low certainty of evidence (class IIb, level C), relying primarily on case studies and expert consensus to inform practice. Our objective was to compare the safety and efficacy of prophylactic anticoagulation, in addition to dual antiplatelet therapy, in the current era of timely primary percutaneous coronary intervention. Electronic databases, including EMBASE, MEDLINE, and Cochrane Library, were systematically searched from January 2012 through June 2022. A total of 7,378 publications were screened, and 5 publications were eventually included in this review: 1 randomized control trial and 4 retrospective studies involving 1,461 patients. Data were pooled using a fixed-effects model and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome of interest was the rate of LVT formation, and the secondary outcomes were the rate of major bleeding and systemic embolism. Pooled analysis showed a significantly lower rate of LVT formation (OR 0.28, 95% CI 0.11 to 0.73, p <0.01) and significantly higher rates of bleeding (OR 2.85, 95% CI 1.13 to 7.24, p = 0.03) in the triple therapy group compared with dual antiplatelet therapy. No significant difference was observed in the rate of systemic embolism between the groups (OR 0.37, 95% CI 0.12 to 1.13, p = 0.08). In this meta-analysis, there is no conclusive evidence to either support or oppose the use of triple therapy for LVT prevention in patients with anterior ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Appropriately powered randomized controlled trials are warranted to further evaluate the benefits of LVT prevention against the risks of major bleeding in this population.

Finding a common definition of heparin resistance in adult cardiac surgery: communication from the ISTH SSC subcommittee on perioperative and critical care thrombosis and hemostasis.

Ensuring adequate anticoagulation for patients requiring cardiac surgery and cardiopulmonary bypass (CPB) is important due to the adverse consequences of inadequate anticoagulation with respect to bleeding and thrombosis. When target anticoagulation is not achieved with typical doses, the term heparin resistance is routinely used despite the lack of uniform diagnostic criteria. Prior reports and guidance documents that define heparin resistance in patients requiring CPB and guidance documents remain variable based on the lack of standardized criteria. As a result, we conducted a review of clinical trials and reports to evaluate the various heparin resistance definitions employed in this clinical setting and to identify potential standards for future clinical trials and clinical management. In addition, we also aimed to characterize the differences in the reported incidence of heparin resistance in the adult cardiac surgical literature based on the variability of both target-activated clotting (ACT) values and unfractionated heparin doses. Our findings suggest that the most extensively reported ACT target for CPB is 480 seconds or higher. Although most publications define heparin resistance as a failure to achieve this target after a weight-based dose of either 400 U/kg or 500 U/kg of heparin, a standardized definition would be useful to guide future clinical trials and help improve clinical management. We propose the inability to obtain an ACT target for CPB of 480 seconds or more after 500 U/kg as a standardized definition for heparin resistance in this setting.

Design and preparation of an artificial vascular scaffold with internal surface modification.

BACKGROUND: Advances in regeneration methods have brought us improved vascular scaffolds with small diameters (φ < 6 mm) for enhancing biological suitability that solve their propensity for causing intimal hyperplasia post-transplantation. METHODS: The correlation between the rehydration ratio of the hydrogel and its material concentration is obtained by adjusting the material ratio of the hydrogel solution. The vascular model with helical structure has been established and analyzed to verify the effect of helical microvascular structure on thrombosis formation by the fluid simulation methods. Then, the helical structure vascular has been fabricated by self-developed 3D bioprinter, the vascular scaffolds are freeze-dried and rehydrated in polyethylene glycol (PEG) solution. RESULTS: The experimental results showed that the hybrid hydrogel had a qualified rehydration ratio when the content of gelatin, sodium alginate, and glycerol was 5, 6, and 3 wt%. The established flow channel model can effectively reduce thrombus deposition and improve long-term patency ratio. After PEG solution modification, the contact angle of the inner wall of the vascular scaffold was less than 30°, showing better hydrophilic characteristics. CONCLUSION: In study, a small-diameter inner wall vascular scaffold with better long-term patency was successfully designed and prepared by wrinkling and PEG modification of the inner wall of the vascular scaffold. This study not only creates small-diameter vascular scaffolds with helical structure that improves the surface hydrophilicity to reduce the risk of thrombosis but also rekindles confidence in the regeneration of small caliber vascular structures.