Heparin Research Articles

Management of post-injury anticoagulation in the traumatic brain injury patient: A scoping review.

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality among trauma patients. The care of these patients continues to be a complex endeavor with prevention of associated complications, often requiring as much attention as that of the treatment of the primary injury. Paramount among these are venous thromboembolic events (VTE) due to their high incidence, additive effect on the risk of morbidity and mortality, and the careful balance that must be utilized in their diagnosis and treatment to prevent progression of the brain injury itself. In this review, we have synthesized the most recent major studies detailing the ideal choice of chemoprophylactic agent, the timing of initiation, and continued monitoring and management strategies through the hospital course and beyond. Additional discussion is provided for subpopulations in which management can vary significantly, including the elderly, critically ill, and obese. Ultimately, current literature supports the use and safety of low molecular weight heparin over unfractionated heparin, especially when dosed using newer assays including anti-Xa levels. The timing of prophylaxis remains important, as the risk of VTE increases with each day that prophylaxis is held. Consensus findings favor initiation within 24-72 h, in the absence of documented progression, life threatening bleeding, or need for major surgical intervention. Despite available data, there continues to be significant variability in practice patterns which we hope to address with this review.

P1155 Safety of Venous Thromboembolism Pharmacological Prophylaxis in Hospitalized Patients with Inflammatory Bowel Disease; A Single Center Retrospective Study (VISCOUS)

Abstract Background Hospitalization secondary to inflammatory bowel disease flare is a significant risk factor for venous thromboembolism (VTE). International guidelines recommend the use of pharmacological VTE prophylaxis; however, the risk of bleeding is unknown. We therefore aimed to evaluate the safety of pharmacological thromboprophylaxis in hospitalized patients with IBD. Methods This was a retrospective cohort study. A chart review of patients’ electronic health records with IBD hospitalized between August 2017 to December 2023 was reviewed. Our primary outcome is evaluating the safety of pharmacological VTE prophylaxis. This was investigated by examining increased bleeding risks during admission, which included worsening bloody stool frequency, drop in hemoglobin (>1g/dL from baseline) and development of hemorrhagic shock after starting VTE prophylaxis. Worsening bloody stool frequency was defined as increased bloody stool frequency >1 from baseline before starting VTE prophylaxis. Finally, any major bleeding was also considered. Results Between August 2017 and December 2023, 1045 patient encounters were reviewed. 524 patients met the study inclusion and exclusion criteria, of which 98 had missing information and 73 were duplicates and could not be included. Finally, 353 patients were included in our study. Mean age 34.7 years, 205 (58%) were female males and mean duration of hospitalization was 9 days. Majority of patients were hospitalized with acute severe ulcerative colitis (ASUC) 213 (60.3%), and 140 (39.7%) had Crohn’s disease (CD) flare. Of the total cohort, 264 (75%) patients received enoxaparin 40 mg for VTE prophylaxis, and the 89 (25%) patients received 5000 units of unfractionated heparin twice a day (figure 1). Eighteen (%5) patients had a history of VTE, and 4 female patients had VTE during admission. None of our cohort had any bleeding events including worsening bloody stool frequency, drop in hemoglobin, major bleeding and development of hemorrhagic shock after starting VTE prophylaxis up to the period patients were discharged. Conclusion we found no increased risk of gastrointestinal bleeding in patients admitted with IBD on pharmacological VTE prophylaxis. Therefore, it is important to reassure healthcare providers about the safety of pharmacological VTE prophylaxis in IBD and adopt strategies that guarantee prophylaxis is administered during hospitalization. Although that a balance should be established between the benefits and risks. References -Pleet JL, Vaughn BP, Morris JA, et al. The use of pharmacological prophylaxis against venous thromboembolism in hospitalised patients with severe active ulcerative colitis. Aliment Pharmacol Ther [Internet]. 2014;39(9):940–948. -Dawwas GK, Cuker A, Schaubel DE, et al. Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease. Blood Adv [Internet]. 2024;8(5):1272–1280. -Kaddourah O, Numan L, Jeepalyam S, et al. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol. 2019;32(6):578–583.

Multifunctional Biological Performance of Electrospun PCL Scaffolds Formulated with Silver Sulfide Nanoparticles.

Our work describes the green synthesis of silver sulfide nanoparticles (Ag2S NPs) and their formulation into polycaprolactone fibers (PCL), aiming to improve the multifunctional biological performance of PCL membranes as scaffolds. For this purpose, an extract of rosemary (Salvia rosmarinus) was employed as a reducing agent for the Ag2S NPs, obtaining irregular NPs and clusters of 5-60 nm, with a characteristic SPR absorption at 369 nm. Ag2S was successfully incorporated into PCL fibers by electrospinning using heparin (HEP) as a stabilizer/biocompatibility agent, obtaining nanostructured fibers with a ca. 500-800 nm diameter. Different amounts of Ag2S NPs (0.05, 0.5, and 1 wt.%) enhanced the nanostructured membranes' surface polarity and mechanical performance, with a controlled ion release after 6 days submerged in PBS solution, determined by cyclic voltammetry. As a result, PCL/HEP/Ag2S scaffolds exhibit high antibacterial performance (80-90%) at early stages of contact (3 h) against E. coli and S. aureus. Also, cytotoxicity analysis demonstrated that the nanostructured membranes are biocompatible and exhibit high fibroblast cell regeneration, which is optimal for their application as scaffolds. To validate the regenerative response of PCL/HEP/Ag2S scaffolds, controlled wounds were induced in Wistar rats, presenting a favorable healing response by contact with PCL/HEP/Ag2S 1%, compared with the untreated wound. Our results indicated that nanostructured scaffolds enable the development of novel nanomaterials with multifunctional biological performance.

Carbon dots with red emission as nanoprobe for sensing of heparin in biofluids and pharmaceutical samples.

Heparin (HEP) is one of the oldest anticoagulant drugs, widely used in clinical settings, particularly in surgery and dialysis machines. Despite its long history, it remains extensively employed in medical practice. This study introduces a selective and cost-effective method for the rapid detection of HEP using red-emission carbon dots (R-CDs). These R-CDs were synthesized through a one-pot hydrothermal method, utilizing neutral red and thiourea for photostability, biocompatibility, and low cytotoxicity. Key parameters affecting the sensing process, including nanoprobe volume, pH, buffer type, and incubation time, were optimized to achieve potential assay conditions. The fluorescence intensity of the nanoprobe at 625 nm gradually decreased as the concentration of HEP increased from 60 to 240 nM. These changes in fluorescence intensity showed a linear relationship with HEP concentration within this range, achieving a limit of detection (LOD) of 5 nM. The proposed nanoprobes facilitate both quantitative and qualitative non-invasive analysis of HEP in various human biofluids, suggesting their potential for broader bioanalytical applications.

Antithrombotic therapy impact on patency and bleeding complications of arteriovenous graft placement in dialysis patients.

Background: Arteriovenous grafts (AVG) can be the only bailout solution for patients who require kidney replacement therapy but are unsuitable for arteriovenous fistula (AVF) creation. Currently, high-level evidence on the effectiveness and safety of antithrombotic therapy in AVG patients is scarce. Materials and methods: Following the PICO (patient; intervention; comparator; outcome) model and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a data search of the English literature in PubMed, SCOPUS, Central Cochrane was conducted, until March 1st, 2023 (PROSPERO Protocol Number: CRD42023401785). Studies on humans with an AVG receiving any kind of antithrombotic medication, reporting on primary and secondary patency rates, and bleeding complications were included. Due to data heterogeneity, a descriptive report of the outcomes was undertaken. Results: Twelve studies, including 22,436 patients with end-stage renal disease (ESRD) and AVG were included, with patient recruitment spanning over a 41-year time-period (1982-2023). Antithrombotic factors included acetylsalicylic acid (ASA), clopidogrel, dipyridamole, warfarin, unfractioned heparin (UFH), and direct oral anticoagulants (DOACs). Ten studies reported on primary patency rates, and two on secondary patency rates. Primary and secondary patency rates (PPR, SPR) were reported better in four studies, similar in three and worse in one study, regarding patients receiving any kind of antiplatelet therapy. Anticoagulation therapy was not associated with increased PPR or SPR, except for one study on apixaban. Patients receiving single or combined antiplatelets versus patients receiving no treatment presented higher bleeding risk in two studies and similar bleeding risk in three studies. Anticoagulation therapy, excluding apixaban, was associated with higher bleeding risk in three studies, when compared to no anticoagulation. Conclusions: Data derived from the current literature were equivocal regarding the use of antiplatelet treatment in patients with AVG. Studies on anticoagulation therapy are confined. Randomized trials with confounder stratification remain crucial for robust long-term data.

Lemierre’s Syndrome Presenting with Multisystem Complications in a Child: A Case Report and Literature Review

Background and Clinical Significance: Lemierre’s syndrome, also known as the “forgotten disease”, is a rare clinical syndrome of septic thrombophlebitis associated with morbidity and mortality. This study reports on a 6-year-old boy diagnosed with Lemierre’s syndrome, providing an in-depth case analysis and a comprehensive review of the current literature on this uncommon condition. Case Presentation: A 6-year-old boy was admitted to the pediatric intensive care unit (PICU) with septic shock, presenting with a high-grade fever of 39.5 °C for 10 days and swelling in the left leg for one week. Additionally, he had a history of swelling in the left mandibular area for five days and a skin rash. His recent medical history was unremarkable, except for decreased activity and oral intake over the past three days. Both his neonatal and past medical histories were unremarkable. Upon admission to the PICU, a multidisciplinary team was assembled to address his condition. Following a comprehensive history, physical examination, and relevant investigations, the child was diagnosed and managed as a case of Lemierre’s syndrome—the first reported case in Saudi Arabia. Treatment included antibiotics, unfractionated heparin infusion, and analgesics. Family members were counseled on the nature, severity, and prognosis of the disease. Despite the optimal treatment given to this patient, the patient died from multiorgan failure as a complication of the disease after an eight-day stay in the PICU. Conclusions: This paper reports the main presenting features and the workup of a 6-year-old male child diagnosed and managed as a case of Lemierre’s syndrome in the Saudi Arabian context. The early recognition of the symptoms of Lemierre’s syndrome and introduction of appropriate treatment in multidisciplinary teamwork are crucial to improve the outcomes of such a life-threating syndrome.

Comparison of adverse drug reactions of heparin and its derivates in the European Economic Area based on data from EudraVigilance between 2017 and 2021.

Hemodialysis patients need long-term frequent use of parenteral anticoagulants, and the side effects need to be taken seriously. This study aimed to assess the reporting of adverse drug reactions (ADRs) following administration of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), fondaparinux, and danaparoid, in relation to their usage in European Economic Area (EEA). The total number of ADRs of each anticoagulant between 2017 to 2021 was collected using data from the EudraVigilance database. The number of hemorrhages, thrombocytopenia, injection-site reaction, liver injury, hypersensitivity and bone disorder were collected, respectively. Usage of these anticoagulants was estimated using sales data from the IQVIA MIDAS database. The reporting rates of ADRs were calculated and compared using χ2-test. Between 2017 and 2021 in the EEA, the overall ADRs reporting rates per 10,000,000 standard units (SU) of UFH, enoxaparin, nadroparin, dalteparin, fondaparinux, and danaparoid were 12.3, 40.8, 23.6, 36.5, 91.4, and 430.0, respectively. There were significant differences among these drugs (χ2 = 7,239.26, p < 0.001). Specifically, hemorrhage and thrombocytopenia were reported at higher rates, ranging from 2.8 to 140.1, and 2.0 to 115.9 per 10,000,000 SU among different anticoagulants. Injection-site reactions and hypersensitivity came in second, between 0.2 - 29.0 and 0.1 - 53.1 per 10,000,000 SU, respectively. The reporting rates for liver injury and bone disorder were reported at low rates. The reporting rates of ADRs for heparin and its derivates were all very low. In comparison, the reporting rate of ADRs for danaparoid and fondaparinux was relatively high. The most commonly reported ADRs were hemorrhage, thrombocytopenia, followed by injection-site reactions and hypersensitivity.

Polycationic γ-Cyclodextrin with Amino Side Chains for a Highly Efficient Anti-Heparin Coagulant.

Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (Kobs) between PyA-γ-CD and heparin as high as 9.85 × 106M-1. The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA-γ-CD not only exhibits nearly complete neutralization activity for unfractionated heparin (UFH), but more importantly, it also effectively neutralizes three LMWHs (dalteparin (Dalte), enoxaparin (Enoxa), and nadroparin (Nadro)) with a broader therapeutic window compared to protamine. The top neutralization activity of PyA-γ-CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA-γ-CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA-γ-CD holds significant potential as a heparin antidote for clinical applications.

Utility of unfractionated sodium heparin in the prevention of disseminated intravascular coagulation

Introduction: disseminated intravascular coagulation (DIC) is a serious disease characterized by a generalized activation of blood coagulation, with sequelae ranging from thrombus formation to severe bleeding.Objective: to analyze the fundamental alternatives for the management of DIC prevention related to the use of unfractionated heparin.Method: data collection was carried out through a search in the digital databases PUBMED, SCIELO (Scientific Electronic Library Online) and GOOGLE ACADEMIC. The articles were downloaded from the aforementioned platforms, and the Zotero system was used to make the corresponding citations and pertinent references.Results: according to the results achieved, the systematic review allowed to obtain a more detailed view of the studies arising from the data search, related to DIC and the use of unfractionated heparin in its prevention. The importance of research related to this drug was highlighted to improve the understanding and treatment of DIC with the aim of reducing its morbidity and mortality.Conclusions: despite unfractionated heparin presenting significant anticoagulant effects in its clinical utility, mainly in emergency situations due to its rapid action, there are few studies available for a better understanding of the management and functionality of UFH against DIC

Severe acute pulmonary embolism in pregnancy.

Pulmonary embolism (PE) is a significant cause of morbidity and mortality in pregnancy and the puerperium. In severe cases, it causes haemodynamic instability and can lead to cardiac arrest due to obstructive shock. Patients with acute PE can be risk stratified to guide their monitoring and treatment; this article focuses on intermediate- and high-risk PE. The criteria for defining high-risk PE can be used unmodified in pregnancy. Diagnostic imaging should not be delayed due to pregnancy. Low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) can be used during pregnancy and breastfeeding, and systemic thrombolysis can be used in obstetric patients, but there are significant bleeding risks and it should be reserved for high-risk PE with hypotension and shock. Although pregnancy and the puerperium are risk factors for PE, it is important to avoid early diagnostic closure, and to consider other causes for the patient's presentation.

The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin-A Randomized, Controlled, Crossover Study.

Exercise increases blood and lymph flow in working muscles, potentially affecting the bioavailability and effect of subcutaneously administered drugs. The aim of this study was to assess the influence of a single exercise session on pharmacokinetics and pharmacodynamics of a single dose of subcutaneously administered unfractionated heparin. In a crossover design, 15 healthy males underwent four experimental days where 15,000 IU of unfractionated heparin was injected subcutaneously into the thigh of the non-dominant leg. Following the injection, one of four interventions was performed in randomized order on four separate occasions, each lasting 1 h: (1) no exercise, (2) double-legged exercise, (3) single-legged exercise with the non-dominant leg (where heparin was injected), and (4) single-legged exercise with the dominant leg. Blood was sampled during and after the interventions and analyzed for activated partial thromboplastin time (aPTT) and plasma heparin via an anti-factor Xa assay. The primary endpoint (maximum aPTT minus baseline aPTT) showed no statistically significant differences between interventions, nor did maximum minus baseline plasma heparin activities. However, after 1 h, change in aPTT was greater, following double-legged exercise compared with no exercise (mean difference 3.5 s, 95% CI 0.8-6.2) and greater after single-legged exercise with the non-dominant leg compared with the dominant (9.7 s, 3.9-15.5). Similar results were observed for plasma heparin activities. In conclusion, exercise does not affect the overall pharmacokinetics and pharmacodynamics of unfractionated heparin but tends to accelerate absorption and hence effect. The study thus underscores that physical exercise affects temporal uptake of subcutaneously administered therapy.

A randomized trial of low-dose thrombolysis, ultrasound-assisted thrombolysis, or heparin for intermediate-high risk pulmonary embolism—the STRATIFY trial: design and statistical analysis plan

BackgroundIntermediate-high risk pulmonary embolism (PE) carries a significant risk of hemodynamic deterioration or death. Treatment should balance efficacy in reducing clot burden with the risk of complications, particularly bleeding. Previous studies on high-dose, short-term thrombolysis with alteplase (rtPA) showed a reduced risk of hemodynamic deterioration but no change in mortality and increased bleeding complications. Catheter-based techniques, including ultrasound-assisted thrombolysis (USAT), and low-dose thrombolysis may offer reasonable efficacy with lower risk. However, studies comparing these methods have been few. This trial aims to address this gap by randomizing patients to three treatment modalities.MethodsMulticenter, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE, excluding those with absolute contraindications to thrombolysis. Patients are eligible for inclusion if they are > 18 years of age, have had symptoms < 14 days, and are able to give informed consent. Patients are allocated 1:1:1 into three treatment strategies: (1) unfractionated heparin (UFH)/low molecular weight heparin (LMWH), (2) UFH/LMWH + 20 mg rtPA/6 h intravenously (IV), or (3) UFH + 20 mg rtPA/6 h via USAT. Co-primary outcomes include reduction in clot burden as assessed by refined Miller score from pre-treatment to follow-up (48–96 h) computed tomography pulmonary angiogram (CTPA) comparing low-dose rtPA (± USAT) groups to UFH/LMWH group (p < 0.01, N = 210) and reduction in refined Miller score on follow-up CT angiography comparing low-dose rtPA by USAT to intravenous rtPA, p < 0.04, N = 140). Secondary outcomes comprise bleeding complications, duration of index admission, FiO2, blood pressure, respiratory and heart rate at the time of follow-up CT angiography, mortality in the three groups, incidence of tricuspid regurgitation pressure gradient < 40 mmHg at 3 months follow-up echocardiography, 6-min walk test at 3 months comparing the three groups, and health-related quality of life at 3 months follow-up comparing the three groups.DiscussionWe hypothesize that in patients with intermediate-high risk PE (1) administration of 20 mg rtPA leads to a greater reduction in clot burden compared to heparins and (2) administration of 20 mg rtPA via USAT results in a greater reduction in clot burden compared to 20 mg rtPA intravenous.Trial registrationClinicalTrials.gov NCT04088292. Registered in September 2019 (retrospectively registered).

A colorimetric sensor for the sensitive and rapid detection of ampicillin based on CS-Cu,Fe/HS nanozyme.

Anovel copper and iron doped containing chitosan and heparin sodium carbon dots (CS-Cu,Fe/HS) nanozyme was formulated through a single-step microwave digestion method. CS-Cu,Fe/HS exhibits excellent peroxidase (POD)-like activity and positive charge characteristics, and it can oxidize the negatively charged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in the presence of H2O2 to produce a green compound (ox-ABTS). Furthermore, CS-Cu,Fe/HS enhances electron transfer and provides additional active sites through the valence state transformations of Fe2+/Fe3+ and Cu2+/Cu+. Interestingly, the POD-like activity of CS-Cu,Fe/HS is inhibited with the introduction of ampicillin (AMP), which may be because the Cu and Fe ions in CS-Cu,Fe/HS form complexes with AMP, leading to changes in the structure or surface properties of the nanozyme, thereby reducing the number of active sites on the nanozyme. Drawing from this, a straightforward and reliable colorimetric sensor was constructed for AMP detection, featuring a linear range of 0.033 to 110μg/mL and a detection limit as low as 11.6ng/mL. The proposed detection method for AMP performed well in real samples, with recoveriesranging from 94.8% to 110.2%.

Unfractionated heparin monitoring by anti-factor Xa versus activated partial thromboplastin time strategies during venoarterial extracorporeal life support.

No clear guidelines exist for unfractionated heparin (UFH) monitoring in adult patients on veno-arterial extracorporeal life support (VA-ECLS) for refractory cardiogenic shock. In this study, we sought to compare outcomes between anti-factor Xa (FXa) and activated partial thromboplastin time (aPTT) strategies for UFH monitoring during VA-ECLS. This is a single-center, retrospective review of VA-ECLS patients who received UFH in the cardiothoracic intensive care unit between July 2019 and November 2023. Standard protocol for UFH titration was aPTT goal of 45-60 sec (n = 52) before September 2021, then transitioned to FXa goal of 0.1-0.2 U/mL (n = 50) thereafter. Inverse probability of treatment weighting was used to balance baseline differences between cohorts. In adjusted analyses, 89.3% of FXa patients and 76.0% of aPTT patients achieved goal range for their respective assay. Total UFH duration (4.0 vs 4.0 days, p = .239) and maximum weight-adjusted UFH dose (9.3 vs 9.4 U/hr/kg, p = .823) remained comparable between adjusted FXa and aPTT cohorts. Moreover, in-hospital mortality (50.3% vs 33.9%, p = .133), major bleeding events (20.6% vs 11.2%, p = .292), and thromboembolic events (30.1% vs 30.1%, p = .998) were not significantly different. Extracorporeal circuit thrombosis and cannula site bleeding were the most frequent events in both groups. Multivariate logistic regression found the FXa strategy was not a significant risk factor for the composite outcome of major bleeding or thromboembolism (OR [95% CI]: 1.539 [0.575, 4.116], p = .393). In adult VA-ECLS patients at our institution, bleeding and thromboembolic complications occurred at a similar rate regardless of which UFH monitoring strategy was utilized. Further studies in larger and more institutionally diverse cohorts are warranted.

Efficacy and Safety of Subcutaneous Unfractionated Heparin Administered Every 8 hours for Venous Thromboembolism Prophylaxis in Reconstructive Head and Neck Tumor Patients: A Systematic Review and 6-Year Institutional Case Series.

Patients with head and neck tumors undergoing free flap reconstructions are at high risk of postoperative venous thromboembolism (VTE). To date, no specific guidelines are available regarding VTE prophylaxis in this patient group. This study aims to contribute to this scarcity of information by reviewing the literature regarding anticoagulation regimens in this patient group and evaluating the efficacy and safety of postoperative subcutaneous heparin dosed at 5,000 units every 8 hours routinely utilized at our institution. PubMed and Embase databases were searched from inception until November 2023. Data were collected and levels of evidence were evaluated according to the Oxford Centre for Evidence Based Medicine guidelines. Additionally, a retrospective review of all patients with head and neck tumors undergoing free tissue transfer at our institution between 2015 and 2021 was performed. Patients were restricted to those receiving 5,000 units of subcutaneous heparin every 8 hours postoperatively. Key outcomes included rates of VTE and surgical site hematoma. This systematic review found 15 studies eligible for inclusion ranging from 1998 to 2023. Anticoagulation regimens were markedly heterogenous. Among the literature, VTE rates reported ranged from 0 to 9.6% and bleeding rates ranged between 3.5 and 29%. Our 6-year institutional analysis revealed 393 total patients. Overall, three episodes of VTE were identified (0.76%) consisting of one deep vein thrombosis and two pulmonary emboli. The overall rate of hematoma was 9.4% with a higher rate of hematoma at the recipient site (8.1%) than the donor site (1.3%). When compared with the existing literature this study found a low rate of VTE and a comparable incidence postoperative hematoma. This suggests that 5,000 units of subcutaneous heparin given every 8 hours may be a safe and effective postoperative anticoagulation regimen for these patients.

The Uses of Antithrombotic Drugs in Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention (PCI)

Atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) pose a significant therapeutic challenge due to the need for effective anticoagulation and antiplatelet therapy. This review examines the strategies used to manage anticoagulation in AF patients undergoing PCI, focusing on dual antiplatelet therapy (DAPT), anticoagulants, and the complexities of combining these therapies. We explore the use of various anticoagulants, including unfractionated heparin (UFH), low molecular weight heparin (LMWH), bivalirudin, warfarin, and direct oral anticoagulants (DOACs), with particular attention to their mechanisms of action, dosing regimens, and potential risks. The review also discusses the use of DAPT in combination with anticoagulation therapy, highlighting the increased bleeding risks associated with these therapies. The duration of DAPT and the option of triple therapy, combining anticoagulation with DAPT, are examined, with a focus on optimizing the duration of treatment to reduce complications. Key challenges, including bleeding risks, kidney function, and the choice of anticoagulant, are addressed, emphasizing the need for individualized treatment plans. Based on the evidence reviewed, we propose recommendations for managing anticoagulation in AF patients undergoing PCI, stressing the importance of balancing thromboembolic risk with bleeding complications. This review aims to provide a comprehensive framework for clinicians in selecting the most appropriate anticoagulation strategy for AF patients undergoing PCI.

Comparative analysis of the hemostatic effect of systemic recombinant Factor VIIa and exogenous fibrin monomer in an experimental model of heparinization and posttraumatic blood loss

This article presents the results of a study of the systemic hemostatic action of recombinant Factor VIIa in a rabbit model of heparin-induced coagulopathy and posttraumatic bleeding, compared to the administration of exogenous fibrin monomer. The coagulopathy was induced by a single intravenous injection of unfractionated heparin at a dose of 150 IU/kg 15 minutes before injury. Recombinant Factor VIIa (270 μg/kg) or fibrin monomer (0.25 mg/kg) was used as systemic hemostatic agents. One hour after administrating the agents, a standardized liver injury was inflicted, followed by an assessment of blood loss characteristics. Using rotational thromboelastometry and coagulation tests, animal venous blood was analyzed for coagulation time, alpha angle, clot formation time, maximum clot firmness, clot density at 10 minutes, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen concentration. Pharmacologically induced coagulopathy resulted in shifts to a hypocoagulable profile, associated with severe blood loss (1.9 times, p = 0.028) and high animal mortality (26.1%, p = 0.022) compared to the control group. Preventive administration of fibrin monomer or recombinant Factor VIIa reduced posttraumatic blood loss (by 5.4 times, p 0.001, and by 2.1 times, p = 0.009, respectively), resulting in a decrease in mortality rates. However, the administration of these agents did not correct the hypocoagulable profile as observed in thromboelastometry and coagulation tests. These data demonstrate the hemostatic effect of both agents, with a more pronounced effect after fibrin monomer administration, and suggest potential use of low doses of fibrin monomer in trauma-related hemorrhage. The mechanism of action of fibrin monomer requires further investigation. Therefore, fibrin monomer, a fibrinogen derivative obtained from blood plasma, could be a valuable candidate for managing wound bleeding in addition to recommended systemic hemostatics.

Comparison of the effectiveness and safety profile of centrifugal and membrane plasma separation in artificial liver therapy with a dual plasma molecular adsorption system

Objective: To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS). Method: A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ² test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result: Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation (P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×109/L vs. 3.5×109/L, P<0.001; mean before and after treatment in the membrane group: 3.5×109/L vs. 3.3×109/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×109/L vs. 119.6×109/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×109/L vs. 97.3 ×109/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion: Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.

Study on the safety profile of dual plasma molecular adsorption system application in patients with liver failure and refractory hyperbilirubinemia

Objective: To retrospectively analyze the dual plasma molecular adsorption system (DPMAS) treatment technology and the laboratory data before and after treatment in patients with liver failure and refractory hyperbilirubinemia, so as to provide a clinical basis for the prediction and prevention of common related complications. Method: A retrospective study was conducted on 161 cases with liver failure and 68 cases with refractory hyperbilirubinemia who underwent DPMAS treatment in our department from October 2022 to July 2024. The general clinical data characteristics, DPMAS treatment status, DPMAS-related complications, and changes in important laboratory indicators before and after the initial DPMAS treatment in both patient groups were analyzed. Results: Among the 229 enrolled cases, 82.53% were male, and the median age was 50 years. The cause of liver failure was hepatitis B virus infection in 84.47%, while hepatitis B accounted for only 51.47% in the other group. There were significant differences in platelets, creatinine, coagulation function, and inflammatory factor-related indicators between the two groups at baseline. The total number of DPMAS treatments given was 471 times. The proportion of albumin used in the initial stage of treatment was significantly higher in patients with refractory hyperbilirubinemia than that in the liver failure group, while the proportion of plasma used in the liver failure group was significantly higher (P<0.001). The most commonly used anticoagulation regimen was unfractionated heparin. A combined anticoagulation therapy regimen was used in 9.3% of the refractory hyperbilirubinemia group. The internal jugular vein was selected in nearly half of the treated cases. A peripheral vascular access pathway was the treatment option in 31.2%. The proportion of centrifugal separation was significantly higher than that of membrane separation (76.22% vs. 23.78%). The incidence rate of DPMAS-related complications was 16%. The most common complication was bleeding, including bleeding at the puncture site (accounting for 32% of the total complications) and bleeding at non-puncture sites (12%), followed by hypotension (22%), allergic reactions (13%) and infections (11%), respectively. The indexes of hemoglobin, platelets, total bilirubin, and C-reactive protein were significantly decreased within 24-48 hours after DPMAS treatment in both groups of patients. The prothrombin time and international normalized ratio were significantly increased in the liver failure group, while fibrinogen was significantly reduced. Conclusion: DPMAS clinical application is generally safe in patients with liver disease. The most common complications are bleeding, hypotension, allergic reactions, and infections, which need to be paid special attention and timely intervention to ensure the safety profile of treatment.

International practice patterns and perspectives on endovascular therapy for the treatment of cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known. Here, we present a comprehensive, international characterization of practice patterns and perspectives on the use of EVT for CVT. A comprehensive 42-question survey was distributed to stroke clinicians globally from May to October 2023, asking about practice patterns and perspectives on the use of EVT for CVT. The overall response rate was 31% (863 respondents of 2744 invited) across 61 countries. The majority of respondents (74%) supported the use of EVT for CVT in certain clinical situations. Key considerations for decision-making in using EVT favored clinical over radiographic/procedural factors and included worsening level of consciousness (86%) and worsening neurological deficits (76%). In the past 3 years, 56% of respondents used EVT for the treatment of CVT, with most (49.5%) involved in two to five cases. Among interventionalists, significant variability existed in the techniques used for EVT (p < 0.001), with aspiration thrombectomy (56%) and stent retriever (51%) being the most used overall. Regionally, interventionalists from China predominantly used intra-sinus heparin (56%), while this technique was most commonly ranked as "never indicated" throughout the rest of the world (23%). Post-procedure, low molecular weight heparin was the most used anticoagulant (83%), although North American respondents favored unfractionated heparin (37%), while imaging was primarily split between magnetic resonance (71.8%) and computed tomography (65.9%) arteriography or venography. Our survey reveals significant heterogeneity in approaches to EVT for CVT, and provides a comprehensive characterization of indications, techniques, and long-term management used by clinicians internationally. This resource will aid in optimizing patient selection and endovascular treatments for future trials.