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Iatrogenic acute limb ischaemia (ALI) in neonates is a rare but severe event with potentially deleterious outcomes. In the neonatal intensive care unit, this risk is increased due to the high rate of catheterisation procedures. ALI management includes pharmacological and non-pharmacological interventions, but no commonly accepted clinical guidelines are available. In the present case, a peripheral catheter was erroneously placed in the left brachial artery of a term infant, causing blockage and ischaemia in the limb. The catheter was immediately removed, the affected limb was elevated and warm compresses were applied to the contralateral limb. The patient was treated with fresh frozen plasma, heparin, iloprost and topical nitroglycerin. Three nerve block procedures were also performed. At 6-8 days of age, significant improvement was observed. The patient was discharged at 17 days of age with near-complete resolution, whereas complete resolution was observed at postdischarge follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years., Methods: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here., Results: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups., Conclusions: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02311231., Competing Interests: Declaration of competing interest Elmir Omerovic reports grants from Astra Zeneca, personal fees from Astra Zeneca, MSD, Bayer, Janssen outside the submitted work. Stefan James reports grants from Astra Zeneca, grants from The Medicines Company, grants from Swedish Heart and Lung Foundation, and grants from Swedish Research Council during the conduct of the study; personal fees from Bayer and grants from Jansen outside the submitted work. Truls Råmunddal reports personal fees from Boston Scientific and personal fees from Abbot outside the submitted work. Ole Fröbert reports personal fees from GE Medical and from Astra Zeneca outside the submitted work. Pontus Lindroos reports personal fees from Astra Zeneca outside the submitted work. Anders Ulvenstam reports personal fees from Boston Scientific outside the submitted work. Matthias Götberg reports grants and personal fees from Volcano Corporation, personal fees from Boston Scientific, and personal fees from Medtronic Corporation outside the submitted work. Oskar Angerås Dr. reports personal fees from Astra Zeneca outside the submitted work. Olie Östlund reports grants from AstraZeneca, grants from The Medicines Company. Cleas Held reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from BristolMyers Squibb, and grants from Merck outside the submitted work. Sasha Koul reports personal fees from Pfizer, personal fees from BMS, and personal fees from Astra Zeneca outside the submitted work. David Erlinge reports personal fees from Astrazeneca and The Medicines Company outside the submitted work. All others co-authors have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin., Materials and Methods: In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups., Results: Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596-0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926-1.391, 0.853-1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265-0.751, 0.410-0.940, respectively)., Conclusions: Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kazuma Yamakawa reported receiving research grants from Asahi Kasei Pharma and Japan Blood Products Organization. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI., Methods: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest., Results: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant., Conclusion: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH., Level of Evidence: Level III, Therapeutic Care Management., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111., Competing Interests: Declaration of competing interest Dr. Watanabe reports lecturer's fees from Abbott Medical Japan during the conduct of the study and from Daiichi Sankyo, Pfizer, Amgen, and Astellas outside the submitted work. Dr. Natsuaki reports honoraria from Abbott Medical Japan, Daiichi Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol-Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr. Morimoto reports lecturer's fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer (New York, New York, United States), Tsumura, and UCB; manuscript fee from Pfizer; and advisory board membership for GlaxoSmithKline, Novartis, and Teijin. Dr. Obayashi reports lecturer's fee from Abbott Medical Japan. Dr. Suwa reports personal fees from Abbott Medical Japan and Daiichi Sankyo outside the submitted work. Dr. Ogita reports personal fees from Daiichi Sankyo, Abbott Medical Japan, and Japan Lifeline outside the submitted work. Dr. Suzuki reports grants from Abbott Medical Japan during the conduct of the study. Dr. Morishima reports honoraria from Abbott Medical Japan and Daiichi Sankyo. Dr. Kimura reports grants from Abbott Medical Japan and Boston Scientific and being an advisory board member for Abbott Medical Japan and Terumo Japan. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Continuous unfractionated heparin is widely used in intensive care, yet its complex pharmacokinetic properties complicate the determination of appropriate doses. To address this challenge, we developed machine learning models to predict over- and under-dosing, based on anti-Xa results, using a monocentric retrospective dataset. The random forest model achieved a mean AUROC of 0.80 [0.77-0.83], while the XGB model reached a mean AUROC of 0.80 [0.76-0.83]. Feature importance was employed to enhance the interpretability of the model, a critical factor for clinician acceptance. After prospective validation, machine learning models such as those developed in this study could be implemented within a computerized physician order entry (CPOE) as a clinical decision support system (CDSS).

Extracellular histones are crucial damage-associated molecular patterns involved in the development and progression of multiple critical and inflammatory diseases, such as sepsis, pancreatitis, trauma, acute liver failure, acute respiratory distress syndrome, vasculitis and arthritis. During the past decade, the physiopathologic mechanisms of histone-mediated hyperinflammation, endothelial dysfunction, coagulation activation, neuroimmune injury and organ dysfunction in diseases have been systematically elucidated. Emerging preclinical evidence further shows that anti-histone strategies with either their neutralizers (heparin, heparinoids, nature plasma proteins, small anion molecules and nanomedicines, etc.) or extracorporeal blood purification techniques can significantly alleviate histone-induced deleterious effects, and thus improve the outcomes of histone-related critical and inflammatory animal models. However, a systemic evaluation of the efficacy and safety of these histone-targeting therapeutic strategies is currently lacking. In this review, we first update our latest understanding of the underlying molecular mechanisms of histone-induced hyperinflammation, endothelial dysfunction, coagulopathy, and organ dysfunction. Then, we summarize the latest advances in histone-targeting therapy strategies with heparin, anti-histone antibodies, histone-binding proteins or molecules, and histone-affinity hemoadsorption in pre-clinical studies. Finally, challenges and future perspectives for improving the clinical translation of histone-targeting therapeutic strategies are also discussed to promote better management of patients with histone-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Peng, Zhang, Chen, Liu, Jiang, Jin, Han, Su and Li.)

Introduction: Endovascular therapy has emerged as a prominent strategy for managing femoropopliteal peripheral artery disease, offering acceptable safety and efficacy compared with open surgical bypass. Both paclitaxel-eluting stents and heparin-bonded covered stents have exhibited enhanced clinical outcomes compared with bare metal stents. However, there is currently a lack of level I evidence comparing the safety and efficacy of paclitaxel-eluting stents and heparin-bonded covered stents. Therefore, the primary objective of this study is to systematically evaluate the efficacy and safety outcomes of these two types of stents., Methods and Analysis: The ELITE trial is a prospective, multicentre, parallel, randomised controlled trial. A total of 450 patients will be recruited. The primary endpoints of the study include primary patency at 1 year post-index procedure., Ethics and Dissemination: Ethical approval for this study was obtained from the Ethics Committee of West China Hospital of Sichuan University (approval number: 2023-1186). The results will be submitted to a major clinical journal for peer review and publication., Trial Registration: ELITE trial was registered on 27 September 2023 in the Chinese Clinical Trials Registry (ChiCTR2300076236)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach., Aim: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis., Methods: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions., Primary Endpoint: the successful completion of hemodialysis without clotting., Secondary Outcomes: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions., Results: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed., Conclusions: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Objectives: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery., Study Design: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms., Results: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001)., Conclusions: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration. This is the fourth known documented case of TMA from a Tiger snake bite in Australia., (© 2024 Asian Pacific Society of Nephrology.)

Introduction: We aim to evaluate the association of early versus late venous thromboembolism (VTE) prophylaxis on in-hospital mortality among patients with severe blunt isolated traumatic brain injuries., Methods: Data from the American College of Surgeons Trauma Quality Program Participant Use File for 2017-2021 were analyzed. The target population included adult trauma patients with severe isolated traumatic brain injury (TBI). VTE prophylaxis types (low molecular weight heparin and unfractionated heparin) and their administration timing were analyzed in relation to in-hospital complications and mortality., Results: The study comprised 3609 patients, predominantly Caucasian males, with an average age of 48.5 y. Early VTE prophylaxis recipients were younger (P < 0.01) and more likely to receive unfractionated heparin (P < 0.01). VTE prophylaxis later than 24 h was associated with a higher average injury severity score and longer intensive care unit stays (P < 0.01). Logistic regression revealed that VTE prophylaxis later than 24 h was associated with significant reduction of in-hospital mortality by 38% (odds ratio 0.62, 95% confidence interval 0.40-0.94, P = 0.02). Additionally, low molecular weight heparin use was associated with decreased mortality odds by 30% (odds ratio 0.70, 95% confidence interval 0.55-0.89, P < 0.01)., Conclusions: VTE prophylaxis later than 24 h is associated with a reduced risk of in-hospital mortality in patients with severe isolated blunt TBI, as opposed to VTE prophylaxis within 24 h. These findings suggest the need for timely and appropriate VTE prophylaxis in TBI care, highlighting the critical need for a comprehensive assessment and further research concerning the safety and effectiveness of VTE prophylaxis in these patient populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The management of anticoagulant therapy in pregnant women with mechanical heart valves (MHVs) is difficult and often challenging even for clinicians experienced in the field. These pregnancies, indeed, are burdened with higher rates of complications for both the mother and the fetus, compared to those in women without MHVs. The maternal need for an optimal anticoagulation as provided by vitamin K antagonists is counterbalanced by their teratogen effect on the embryo and fetus. On the other hand, several concerns have been raised about the efficacy of heparins in pregnant women with MHVs, considering the high risk of thrombotic complications in these patients. Therefore, numerous clinical issues about the management of pregnant women with MHVs remain unanswered, such as the selection of the best anticoagulant agent, the optimal anticoagulation levels to be achieved and maintained, and the evaluation of long-term effects for both the mother and the fetus. Based on a comprehensive review of the current literature, the Italian Federation of the Centers for the Diagnosis and the Surveillance of the Antithrombotic Therapies (FCSA) proposes experience-based suggestions and expert opinions. Particularly, this consensus document aims at providing practical guidance for clinicians dealing with pregnant women with MHVs, to optimize maternal and fetal outcomes while guaranteeing adequate anticoagulation. Finally, FCSA highlights the need for the creation of multidisciplinary teams experienced in the management of pregnant women with MHVs during pregnancy, delivery, and postpartum , in order to better deal with such complex clinical issues and provide a comprehensive counseling to these patients., Competing Interests: A.S. received honoraria for lectures, manuscript writing, and/or participation on advisory board from Daiichi Sankyo, Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Viatris, Sanofi, Werfen, Boehringer-Ingelheim, Alexion, and Roche. All other authors have nothing to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality. For optimal thromboprophylaxis treatment for hospitalized patients, especially those with severe COVID-19 symptoms, it is still unclear whether to use full- or therapeutic-dose versus prophylactic-dose anticoagulation therapy. The study aim was to evaluate the efficacy and safety of unfractionated heparin (UFH) for thromboprophylaxis in severe degree of COVID-19., Methodology: In this cross-sectional study, the medical records of 160 COVID-19 patients at the COVID-19 Emergency Hospital Wisma Atlet, Jakarta, from March to August 2021, were collected. The predetermined inclusion criteria for patients were severe COVID-19 infection; age > 18 years; positive D-dimer level > 400 ng/mL; high-flow nasal cannula (HFNC) oxygenation; IMPROVE bleeding risk score < 7; and willingness to participate in the study. The primary outcome was activated partial thromboplastin time (APTT) target achievement, oxygenation changed to nasal cannula or ended with room air, mortality rate, and the principal safety criterion was presence of bleeding., Results: Of 160 subjects, 63.8% were male and 45.6% were aged 45-59 years old. Obesity was the most common comorbidity at 45.6% Among all subjects, 9.4% experienced bleeding, with hematuria being the most frequent type at 66.7%. All subjects released HFNC, and no deaths were reported., Conclusions: It can be concluded that administration of therapeutic doses of heparin in patients with severe COVID-19 had a low risk of bleeding and no patients were reported to have died. However, further investigation is needed to determine the long-term effects of therapeutic doses of anticoagulants., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Hari Hendarto, Femmy Nurul Akbar, Prasetyo Widhi Buwono, Putri Adara Yasmin, Mega Halida, Efriadi Ismail, Nurul Rakhmawati, Hilman Tadjoedin.)

Introduction: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock., Methods and Analysis: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers., Ethics and Dissemination: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences., Trial Registration Number: ACTRN12622000499785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: If left untreated, burn injuries can deepen or progress in depth within the first 72 hours after injury as a result of increased wound inflammation, subsequently worsening healing outcomes. This can be especially detrimental to warfighters who are constrained to resource-limited environments with delayed evacuation times to higher roles of care and more effective treatment. Preventing this burn progression at the point of injury has the potential to improve healing outcomes but requires a field-deployable therapy and delivery system. Subcutaneous therapies known to treat inflammation delivered local to the wound site may prove to be one such avenue for success., Materials and Methods: Seven Yorkshire-cross swine received partial-thickness burn injuries using a previously established contact burn model. Each animal received one of the seven therapies: (1) saline, (2) heparin, (3) ibuprofen, (4) erythropoietin, (5) resolvin, (6) rapamycin, and (7) placental extract, all of which are either currently employed or are experimental in field use and indicated to treat inflammation. Treatments were delivered subcutaneously on the day of injury and 24 hours post-injury to simulate a prolonged field care scenario, before potential evacuation. Animals and wound development were observed for 28 days before euthanasia. Throughout the course of the study, wounds were observed macroscopically via non-invasive imaging. Histological analyses provided the critical metric of burn progression. Treatment success criteria were designated as the ability to prevent burn progression past 80% of the dermal depth in two of the three treated wounds, a clinically relevant metric of burn progression., Results: It was determined that the applied model successfully created reproducible partial-thickness burn injuries in this porcine study. No significant differences with regard to lateral wound size or the rate of lateral wound closure were observed in any treatments. Several treatments including resolvin, rapamycin, ibuprofen, and erythropoietin successfully reduced burn progression to less than 80% of the dermal depth in two of the three wounds, 24 hours after injury., Conclusions: This report employs an established model of porcine contact burn injury in order to test the ability of local subcutaneous delivery of therapeutics to prevent burn progression at the point of injury, via what is believed to be the inhibition of inflammation. Several treatments successfully prevented burn progression to a full-thickness injury, potentially improving wound healing outcomes in a simulated battlefield scenario. Subcutaneously administered therapies combating burn-induced inflammation at the point of injury may serve as a field-deployable treatment modality to improve warfighter recovery and return to duty., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Declaration of competing interests A.M. received payments made to his institution from i-SEP for consulting fees and from LFB, Aguettant, Viatris, and Pfizer for lecture fees, all outside the submitted work. F.M. reports institutional fees from Stago, Werfen, Nodia, Roche Sysmex, and Bayer. He also reports speaker fees from Boehringer-Ingelheim, Bayer Healthcare, Bristol-Myers Squibb-Pfizer, Diagnostica Stago, Sysmex, and Aspen, all outside the submitted work. T.L., E.D.M., I.G.T., and M.H. have no competing interests to disclose.

Competing Interests: Declaration of competing interests None of the authors have any financial or nonfinancial competing interest in connection with this study. E.B. has no conflict of interest in connection with the work submitted. In addition, E.B. received, during the past 3 years, congress registration and travel fees from Swedish Orphan Biovitrum and Takeda and lecture and consulting fees from Viatris and Aguettant. J.-C.R. has no conflict of interest in connection with the work submitted. In addition, J.-C.R. received, during the past 5 years, congress registration and travel fees from Werfen and Edwards, lecture and consulting fees from Vifor Pharma, and research grant from i-Sep. B.R. has no conflict of interest in connection with the work submitted. K.L. has no conflict of interest in connection with the work submitted. In addition, K.L. received, during the past 3 years, congress registration from Pfizer (once in 2022) and both congress registration and travel fees from Advanz Pharma/Correvio (once in 2021) and from AOP Health (once in 2024).

Adherence to guideline recommendations for venous thromboembolism prophylaxis (VTE) in hospitalized medical patients is suboptimal despite national policies and institutional interventions. The aim of this quality improvement project was to improve adherence to guidelines and decrease the overuse of VTE prophylaxis in order to reduce the institutional cost for heparins. A multidisciplinary anticoagulation stewardship program (ACSP) using the audit and feedback strategy was implemented on the medicine inpatient units at a teaching hospital in Canada. The primary outcome measure was a comparison, pre and post introduction of the ACSP, of the costs per 6-month period for prophylactic dose enoxaparin and unfractionated heparin on the medicine units. The balancing measures were the 90-day VTE rate and major bleeding rate during the hospitalization. Six months after the implementation of the ACSP, the cost was decreased by >50 % without any observed negative impact on patient safety. This study demonstrates the potential for anticoagulation stewardship programs to optimize the use of VTE prophylaxis and reduce the associated costs and risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression., Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events., Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase)., Conclusion: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE., Trial Registration: JRCT Identifier: jRCTs031180124., Competing Interests: YT, TS, and HF received honoraria from Daiichi Sankyo. KY received a research grant from Daiichi Sankyo. KH received honoraria and a research grant from Daiichi Sankyo. KF received honoraria from Daiichi Sankyo for consultation., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lumboperitoneal shunt (LPS) has been an effective treatment of idiopathic normal pressure hydrocephalus (iNPH) but sometimes causes serious complications. Here we present the first reported case of cerebral venous thrombosis (CVT) after LPS. A 76-year-old man underwent LPS for iNPH and a week later developed weakness of the right arm and a generalized tonic-clonic seizure. Brain computed tomography and magnetic resonance imaging showed bilateral subdural hematoma (SDH) and left cortical vein thrombosis. Intravenous heparin was administered, followed by surgical evacuation of the SDH. The patient experienced gradual improvement and was subsequently discharged. It is conceivable that overdrainage of cerebrospinal fluid led to the development of both SDH and CVT. CVT is potentially fatal and should be recognized early as a possible complication after LPS to allow prompt treatment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Acute hypertriglyceridemia is considered a category III indication for plasmapheresis. The use of plasma as replacement fluid (RF) has been suggested to replace the consumed lipoprotein lipase. Heparin when used as an anticoagulant could possibly release lipoprotein lipase, thereby increasing triglyceride clearance., Methods: The impact of RF (albumin vs fresh frozen plasma (FFP) and anticoagulant (ACD-A vs. heparin) on triglycerides following plasmapheresis in 27 patients with severe hypertriglyceridemia (SHTG) was investigated. A paired study of four patients with recurrent SHTG was conducted, evaluating continuous (Optia) versus intermittent flow plasmapheresis (Haemonetics)., Results: Shorter procedures positively impacted triglycerides (TG) drop post-sessions p < 0.05. In albumin sessions, patients who used heparin demonstrated significantly greater drop in TG and required less sessions than did those with citrate p < 0.05. In heparin sessions, patients who used albumin demonstrated significantly greater drop in triglycerides and required less sessions than did those with FFP p < 0.05. Three of six patients who used FFP and heparin showed a triglyceride drop of 11.7% following three sessions and a 50% drop with one albumin session. Compared with Haemonetics, Optia removed comparable volumes of plasma in less time, processing smaller blood volumes and using less citrate p < 0.05. Patients demonstrated significantly lower drop in TG and required more sessions with Haemonetics than they did with Optia p < 0.05., Conclusion: Shorter procedure was the main predictor for effective TG clearance. This can be achieved by continuous apheresis technology, particularly when using albumin as RF. TG removal via Optia seems to be optimized by using heparin., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Background: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications., Methods: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications., Results: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported., Conclusions: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively., Levels of Evidence: Level II, retrospective study., Competing Interests: Conflicts of interest None of the authors have financial disclosures related to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival., Background: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low., Methods: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort., Results: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests ( P =0.0017 overall, P =0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors., Conclusions: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: An association between blunt head trauma and cerebral venous sinus thrombosis (CVST) has been recognized, but its symptoms are nonspecific and the duration of symptoms remains unclear. Anticoagulation therapy is not considered necessary in most cases of traumatic CVST; however, this is controversial. The aim of this study was to describe the clinical characteristics and outcomes of children with CVST after isolated head trauma., Methods: The records of pediatric patients with isolated head trauma admitted for observation at 3 medical centers between January 2018 and May 2023 were reviewed retrospectively. CVST was diagnosed on MR venography (MRV). Clinical presentation, therapeutic management, and outcomes were evaluated in patients who had follow-up MRV., Results: Of 260 pediatric patients with head trauma admitted to the 3 hospitals, 26 patients underwent MRV and 8 (30.8%) were diagnosed with CVST. One patient was treated with heparin, while the others received conservative treatment. All patients were discharged home asymptomatic. MRV performed during follow-up displayed complete recanalization in all cases, except for 1 case with partial recanalization. The median hospital stay was longer in patients with CVST than in those without CVST (9.5 vs 3.0 days, p = 0.001)., Conclusions: The length of stay of pediatric patients with traumatic CVST was prolonged compared with those without CVST, but most patients had good outcomes with spontaneous recanalization following conservative treatment.

Background: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure., Aim: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy., Methods: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t -tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups., Results: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality., Conclusion: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Víteček et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The awareness of nonocclusive thrombus has increased with the increasing frequency of imaging methods used for acute ischemic stroke; however, the best treatment for nonocclusive thrombi is still unknown. In this study, we examined how anticoagulants affect supra-aortic artery nonocclusive thrombus and clinical outcomes., Materials and Methods: This study included 52 patients with transient ischemic attack or stroke who were diagnosed with nonocclusive thrombi on computed tomography angiography at admission. Patients were treated with anticoagulant treatment and grouped according to treatment modality (either unfractionated heparin or low molecular weight heparin) and treatment duration. Primary safety outcome was major bleeding defined as immediate and clnically significant hemorrhage. Anticoagulant treatment was continued until the thrombus was resolved as determined by consecutive weekly computed tomography angiography controls. After thrombus resolution, treatment was directed according to the underlying etiology. Antiaggregation treatment was the preferred treatment after thrombus resolution for patients with no observed etiology., Results: The affected internal carotid arteries were most frequently located in the cervical segment (48 %). Complete resolution was achieved within 2 weeks in 50 patients (96 %). The involved vasculature included the following: the extracranial carotid artery segments (n = 26, 50 %), intracranial ICA segments (n = 10, 19 %), basilar artery segments (n = 8, 15 %) and MCA segments (n = 7, 13 %). The most common underlying pathologies were atherosclerosis (n = 17), atrial fibrillation (n = 17), undetermined embolic stroke (n = 8), dissection (n = 7), and malignancy (n = 2). No symptomatic intra- or extracranial bleeding complications due to anticoagulant use were observed in any patient during the study period. A good functional outcome (modified Rankin scale score 0-2) was achieved in 49 patients (94 %) at 3 months. There was no significant difference between treatment type and duration in terms of reinfarction (p = 0.97 and p = 0.78, respectively)., Conclusion: Anticoagulant treatment is safe and effective in symptomatic patients with intracranial or extracranial artery nonocclusive thrombus, regardless of the anticoagulant type, thrombus location and size., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE)., Purpose: The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol., Methods: Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance., Interventions: Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol., Results: The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period., Conclusions: A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Heparin resistance (HR) is a common finding in pediatric cardiac surgery and generally refers to decreased sensitivity to heparin. Antithrombin (AT) deficiency is considered the primary mechanism of HR; however, the etiology of HR may be multifactorial. Early identification of HR might help optimize heparin anticoagulation management. This study aimed to develop a predictive nomogram for HR in neonates and young infants undergoing cardiac surgery., Methods: From January 2020 to August 2022, a total of 296 pediatric patients 1 to 180 days of age were included in this retrospective study. The patients were randomly divided into development and validation cohorts in a 7:3 ratio. Univariable logistic regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regularization were used for variable selection. A multivariable logistic regression was performed to identify predictors and establish a nomogram to predict HR risk. Discrimination, calibration, and clinical usefulness were assessed in the development and validation cohorts., Results: After the multistep variable selection, AT activity, platelet count, and fibrinogen were predictors for HR in neonates and young infants. The prediction model constructed using these 3 factors achieved an area under the receiver operating characteristic curve (ROC-AUC) of 0.874 and 0.873 in the development and validation cohorts. The Hosmer-Lemeshow test did not find evidence of a lack of fit ( P = .768). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the model performed well in neonate and infant subgroups., Conclusions: A nomogram based on preoperative variables was developed to predict the HR risk in neonates and young infants undergoing cardiac surgery. This provides clinicians with a simple tool for the early prediction of HR, which may help optimize heparin anticoagulation strategies in this vulnerable patient population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

COMT inhibitors are commonly used to improve the effectiveness of levodopa in treating Parkinson's disease by inhibiting its conversion to 3-O-methyldopa. Because of the serious side effect of nitrocatechol COMT inhibitors, it is necessary to develop non-nitrocatechol COMT inhibitors with a higher safety profile. Heparin has been observed to bind to COMT. However, the exact functional significance of this interaction is not fully understood. In this study, the contribution of different substitution of heparin to its binding with COMT was investigated. In vitro and in vivo, heparin oligosaccharides can bind to COMT and inhibit its activity. Furthermore, we enriched the functional heparin oligosaccharides that bind to COMT and identified the sequence UA2S-GlcN(S/Ac)6(S/H)-UA2S-GlcNS6(S/H)-UA2(S/H)-GlcNS6S as the characteristic structural domain of these functional oligosaccharides. This study has elucidated the relationship between the structure of heparin oligosaccharides and their activity against COMT, providing valuable insights for the development of non-nitrocatechol COMT inhibitors with improved safety and efficacy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fister et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Continuous renal replacement therapy (CRRT) is often disrupted due to various factors, such as patient-related issues, vascular access complications, treatment plans, and medical staff factors. This unexpected interruption is referred to as non-selective filter stoppage and can result in additional treatment expenses. This study conducted a retrospectively analyzed 501 CRRT filters used in 62 patients with severe burns, lifespan and therapeutic effect of all filters were mainly analyzed, used logistic regression analysis was performed to identify risk factors associated with non-selective cessation filters. Out of 493 filters, 279 cases received heparin (56.60%), the median lifespan of the filter was 14.08 h (25th, 75th quantile: 7.30, 21.50); 128 cases were treated with nafamostat mesylate (26.00%), and the median lifespan of the filter was 16.42 h (10.49, 22.76); 86 cases were treated with sodium citrate (17.40%), and the median lifespan of the filter was 31.06 h (19.25, 48.75). In addition, significant differences were observed in the electrolyte index, renal function index, and procalcitonin levels before and after treatment with a single filter (P < .001). Multivariate logistic regression showed that the risk of non-selective cessation of sodium citrate anticoagulants was lower than that of heparin anticoagulation. Overall, CRRT is progressively becoming more prevalent in the treatment of patients with severe burns. The lifespan of individual filters and total patient treatment duration showed a consistent upward trend. The filter's lifespan was notably greater during sodium citrate anticoagulation when compared to nafamostat mesylate and heparin, meanwhile notably reducing the risk of non-selective cessation. Therefore, we recommend sodium citrate for anticoagulation in patients without any contraindications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association.)

Around 10% of patients with acute coronary syndrome are treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants for various indications. The initial management of these patients is highly complex, and new guidelines specify that, only during percutaneous coronary intervention, a bolus of unfractionated heparin is recommended in one of the following circumstances: (1) if the patient is receiving a non-vitamin K antagonist oral anticoagulant; or (2) if the international normalized ratio is<2.5 in a patient being treated with a vitamin K antagonist. In this review, we report on five key messages essential for the management of these patients. There are no randomized studies to date, and we propose two diagnostic and/or therapeutic decision algorithms. However, randomized studies are needed to validate these strategies., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Venoarterial extracorporeal membrane oxygenation is increasingly used for mechanical circulatory support during lung transplant. Optimal intensity of intraoperative anticoagulation would be expected to mitigate thromboembolism without increasing bleeding and blood product transfusions. Yet, the optimal intensity of intraoperative anticoagulation is unknown. We performed a retrospective cohort study of 163 patients who received a bilateral lung transplant at a single center. We categorized the intensity of anticoagulation into 4 groups (very low to high) based on the bolus dose of unfractionated heparin given during lung transplant and compared the rates of intraoperative blood transfusions and the occurrence of thromboembolism between groups. When compared to the very low-intensity group, each higher intensity group was associated with higher red blood cell, fresh frozen plasma, and platelet transfusions. The occurrence of thromboembolism was similar across groups. These preliminary data suggest that lower intensity anticoagulation may reduce the rate of intraoperative blood transfusions, although further study is needed., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing., Methods: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added., Results: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 ( p < .0001) and 0.95 ( p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]., Conclusion: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Off-pump coronary artery bypass grafting (OPCABG) was introduced many years ago aiming to reduce the known complications of conventional on-pump coronary surgeries. Heparin is required during the procedures, but the available protocols have diverse dosage regimens. The primary objective of this systematic review is to examine the effect of different heparin doses on the outcomes of OPCABG., Evidence Acquisition: MEDLINE and EMBASE were searched. Four reviewers identified eligible clinical trials. Two reviewers extracted data and independently assessed the risk of bias using Cochrane tool. The primary outcome was the activated clotting time (ACT) at three minutes. The secondary outcomes were proportion of patients requiring blood products and the length of hospital stay. An aggregate data approach was used., Evidence Synthesis: Three single-center randomized studies recruiting 256 patients were included. The studies compared low-dose (1.5-2 mg/kg) and high-dose (3 mg/kg) heparin boluses. The overall mean difference for ACT after three minutes between low- and high-dose heparin is - 126.16 (95% CI: - 142.19, - 110.14). The proportion of patients requiring blood products after surgery [odd ratio 1.27 (95% CI: 0.69, 2.32)] or the overall length of stay [mean difference -0.15 (95% CI: -0.84, 0.53)] did not differ between the heparin doses., Conclusions: In OPCABG, high-dose compared with low-dose heparin did not affect the utilization of more blood products or increased the overall length of stay. Unsurprisingly, ACT values were higher in the high-dose heparin group. Larger and adequately powered randomized clinical trials are indicated to resolve the uncertainty., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli -associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Background: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation., Methods: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding., Results: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04., Conclusion: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Free tissue transfer has an established place in oncologic head and neck surgery. However, the necessity and specific regimen of perioperative thromboprophylaxis remain controversial. Here, the risk of postoperative hemorrhage contrasts with vascular pedicle thrombosis and graft loss. This work compares three different heparin protocols (A-C) with regard to postoperative complications., Patients and Methods: A retrospective analysis of our free flap transplants between 2004 and 2023 was conducted. Inclusion criteria were thromboprophylaxis with (A) 500 IU/h unfractionated heparin (UFH), (B) low-molecular-weight heparin (LMWH) once daily, and (C) LMWH once daily with additional immediate preoperative administration. Primary endpoints were the incidence of postoperative bleeding and hematoma and the appearance of flap thrombosis., Results: We evaluated 355 cases, 87 in group A, 179 in group B, and in group C 89 patients. Overall, postoperative bleeding occurred in 8.7% of patients, and 83% underwent hemostasis under intubation anesthesia, with no significant difference between groups (p = 0.784). Hematoma formation requiring revision was found in 3.7% of patients (p = 0.660). We identified postoperative hematoma as a significant influencing factor for venous pedicle thrombosis (OR 3.602; p = 0.001). Venous and arterial flap thrombosis in the graft vessel showed no difference between the groups (p = 0.745 and p = 0.128)., Conclusions: The three anticoagulation regimens appear to be equivalent therapy for the prevention of thrombosis without significant differences in postoperative bleeding. The use of LMWH with additional preoperative administration can, therefore, be administered in free flap reconstruction.