Treatment of portal vein thrombosis in cirrhosis is associated with no survival advantage: a retrospective controlled study.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is associated with increased mortality post-transplant, but treatment of the clot is not definitively associated with improvement in mortality. We aimed to assess the effect of anticoagulation (AC), transjugular intrahepatic portosystemic shunt (TIPS), or best supportive care only (SCO) as treatment options in patients with PVT and cirrhosis. METHODS: This was a retrospective controlled cohort study from a large urban health system. Patients with cirrhosis and PVT were identified and analyzed based on treatment provided (1) AC, (2) TIPS, and (3) SCO. Outcomes included patent portal vein at the end of follow-up and overall mortality. RESULTS: 150 patients on AC, 93 who underwent TIPS, and 172 who received SCO were analyzed. Final portal vein (PV) patency was not significantly different by treatment group in those with partial obstruction at presentation (p = 0.64), while any treatment improved final patency over SCO in those presenting with complete obstruction (p = 0.01). Rate of survival, transplant-free survival, and successful liver transplantation were not different between treatment groups. CONCLUSION: In our cohorts, treatment of PVT versus SCO showed no impact on survival in those presenting with partial obstruction of the PV. In those with complete obstruction, any treatment was more effective than SCO in achieving patency of the PV, but overall survival was no different. PVT may not be a pathologic mechanism that causes worsening of liver disease but may be an event in the progression that in itself is not directly responsible for worsening liver function.

Association of Activated Clotting Time-Guided Anticoagulation with Complications during Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to reduce the risk of thromboembolic events. Despite its historic role, activated clotting time (ACT) remains a widely used heparin monitoring method. Systematic evidence on the association of ACT-guided monitoring with hemorrhagic or thromboembolic complications does not exist. DESIGN: Systematic literature review and meta-analysis (Scopus and PubMed, July 2023). SETTING: All cohort studies. PARTICIPANTS: Patients receiving ECMO support. INTERVENTION: Anticoagulation monitoring with ACT. MEASUREMENTS AND MAIN RESULTS: We identified 3,177 publications, with 8 studies reporting the average ACT values for patients with and without bleeding. Meta-analysis revealed no significant difference in the compared groups (SMD = 0.69; 95% CI -0.05 to 1.43, p = 0.069; I2 = 87.4%). Three studies (n = 117 patients) reported on the average ACT values for patients with thrombosis, without significant differences in ACT between patients with and without thrombosis (SMD = 0.47; 95% CI -0.50 to 1.44, p = 0.342; I2 = 81.1%). CONCLUSIONS: Even though ACT is a widely used heparin monitoring tool, the evidence on its association with hemorrhagic or thromboembolic events is still controversial and limited. Further studies are essential to elucidate the role of ACT in anticoagulation monitoring during ECMO support.

Chronic Anticoagulation in Patients Who Have Atrial Fibrillation Undergoing Outpatient Total Knee Arthroplasty: A Retrospective Matched Cohort Study.

BACKGROUND: Patients who have atrial fibrillation frequently require long-term anticoagulation with warfarin or a direct-acting oral anticoagulant (DOAC), such as apixaban or rivaroxaban, to avoid vascular complications. However, the impact of anticoagulant use on postoperative complications following total knee arthroplasty (TKA) in an outpatient setting has not been thoroughly elucidated. The purpose of this study was to examine the impact of anticoagulant use on early postoperative complications among atrial fibrillation patients undergoing outpatient TKA. METHODS: An insurance claims database was queried to identify all patients who underwent outpatient TKA between January 2010 and April 2022. There were two cohorts of patients, with associated 1:1 matched controls, who had atrial fibrillation and filled a prescription of either warfarin (N = 4,396) or DOAC (N = 5,383) for at least 30 days. The mean age was 70 years (range, 51 to 84 years) and 47.9% were women in the warfarin cohort, while the mean age was 70 years and 49.2% were women in the DOAC cohort. Postoperative 30-day medical and 90-day surgical complications were subsequently compared. RESULTS: Patients on warfarin had a higher incidence of pulmonary embolism (1.1 versus 0.2%, P < 0.001) and a lower incidence of TKA revision (0.1 versus 0.4%, P = 0.003) than matched controls. Similarly, patients on DOACs exhibited a higher incidence of pneumonia (1.4 versus 0.6%, P < 0.001) and myocardial infarction (3.2 versus 1.5%, P < 0.001) and a lower incidence of wound dehiscence (0.1 versus 0.5%, P < 0.001), joint infection (0.4 versus 0.9%, P = 0.002), and TKA revision (0.1 versus 0.4%, P = 0.002) than matched controls. CONCLUSIONS: Atrial fibrillation patients on long-term anticoagulants undergoing outpatient TKA experience higher rates of medical complications and lower rates of surgical complications than matched controls. Thus, patients on long-term anticoagulants may be considered for outpatient TKA, but should be counseled appropriately on associated medical risks.

A 10-year cross-sectional study showed that anti-coagulation therapy was not always of value when treating paediatric cases with septic cerebral venous thrombosis.

AIM: Cerebral venous thrombosis (CVT) is a rare complication of ear, nose and throat (ENT) infections. Although recent guidelines recommend the systematic use of anti-coagulation therapy (ACT) in the treatment of these CVT, literature data are scarce. The present study's objective was to determine the value of ACT in achieving recanalisation after thrombosis and its effect on patient outcomes. METHODS: All paediatric patients with CVT and a concomitant ENT infection who attended Lille University Hospital (Lille, France) between January 2012 and December 2021 were retrospectively included. RESULTS: We included 43 children (63% boys), with a mean age of 4 years. The most frequent infection was mastoiditis (54%). ACT was initiated in 23 patients (53%), one of whom had an intracranial haemorrhage. Partial or full recanalisation was observed in 33 (80%) of the 41 survivors. In patients with no neurological signs and symptoms on admission and in patients with mastoiditis-related CVT, the clinical and radiological outcomes were favourable and did not differ according to the administration of ACT. Likewise, ACT did not appear to influence the recanalisation rate or sequelae. CONCLUSION: ACT was not necessary for all patients with mastoiditis-related CVT and those with no neurological signs and symptoms on admission.

Intravenous enoxaparin guided by anti-Xa in venovenous extracorporeal membrane oxygenation: A retrospective, single-center study.

BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.

Impacts of COVID-19 on hemostasis: coagulation abnormalities and management perspectives.

The COVID-19 pandemic caused by SARS-CoV-2 has transcended its initial characterization as a respiratory illness, revealing substantial implications for hemostasis and coagulation pathways. COVID-19-associated coagulopathies have emerged as critical determinants of disease severity and prognosis, presenting a multifaceted challenge in clinical management. This paper aims to elucidate the intricate interplay between COVID-19 and hemostasis, delving into the underlying mechanisms of coagulation abnormalities, exploring the spectrum of thrombotic complications, and discussing evolving management strategies. Therapeutic interventions and anticoagulation strategies tailored for managing COVID-19-related coagulopathies form a significant focus, encompassing prophylactic and therapeutic approaches, heparin-based therapies, and individualized treatment paradigms. This paper underscores the imperative for ongoing research endeavors to refine diagnostic modalities, identify novel therapeutic targets, and ascertain long-term sequelae of COVID-19-induced coagulation abnormalities. Ultimately, a comprehensive understanding of the intricate relationship between COVID-19 and hemostasis is pivotal in devising effective management strategies to mitigate thrombotic risks, improve clinical outcomes, and pave the way for tailored interventions in affected individuals.

Thromboembolic Risk in Sinus Rhythm: A New Paradigm in Light Chain Cardiac Amyloidosis.

Thromboembolic risk is increased in cardiac amyloidosis, and this goes beyond the occurrence of atrial fibrillation in these patients. A 56-year-old man was admitted to our hospital for a presyncopal episode. Clinical and instrumental findings led to a diagnosis of light chain cardiac amyloidosis. Hospitalization was complicated by ischemic stroke resulting from embolization of a left atrial thrombus, that occurred in sinus rhythm. This case highlights the importance of a new diagnostic strategy for thromboembolic risk stratification in patients with cardiac amyloidosis. Left atrial strain assessment should be implemented in patients with cardiac amyloidosis to predict the occurrence of thromboembolic events.

Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience.

Background: Regional citrate anticoagulation (RCA) has emerged as a treatment modality that reduces bleeding risk and filter clotting. With initial experience of using RCA with continuous renal replacement therapy (CRRT), we have formulated a working protocol based on published literature. Objective: The study aimed to evaluate the protocol for routine use of RCA during CRRT requiring anticoagulation and evaluation of filter life. Methodology: It is a single-center, open-label, prospective, non-randomized, non-interventional, single-arm, observational study conducted at a tertiary care hospital between September 2022 and July 2023. All adult patients with acute kidney injury (AKI) or hyperammonemia requiring CRRT and necessitating the use of anticoagulation were enrolled in the study. The study used Prisma Flex M100 AN 69 dialyzer on Prisma Flex (Baxter) CRRT machines during continuous venovenous hemodiafiltration (CVVHDF). The targeted CRRT dose in all the study patients was 25-30 mL/kg/hour. Based on the published literature, we have developed a working protocol (Appendix 1) for managing patients on CRRT using RCA. Results: A total of 159 patients were analyzed for the study. The median [interquartile range (IQR)] filter life using RCA was 30 (12-55) hours. Filter clotting was observed in 33.3% of patients. Citrate accumulation was present in 52.25% of patients, but no CRRT was discontinued as citrate accumulation resolved after following the corrective steps in the protocol. None of the patients had citrate toxicity. Chronic liver disease (CLD) (p ≤ 0.001) and those who were post-living donor liver transplant recipients (p = 0.004) had a statistically significant increase in citrate accumulation. Also, patients who had higher lactate at baseline (6 hours post-CRRT initiation), had a higher chance of citrate accumulation. Conclusion: Our RCA protocol provides a safe approach to regional anticoagulation during CRRT in critically ill patients. How to cite this article: Pachisia AV, Kumar GP, Harne R, Jagadeesh KN, Patel SJ, Pal D, et al. Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience. Indian J Crit Care Med 2024;28(9):859-865.

Bivalirudin as an anticoagulation strategy for acute hemodialysis in children: Two cases with a summary of recent literature.

Unfractionated heparin is the most used anticoagulative agent for extracorporeal settings in children, including acute hemodialysis modalities. In certain situations, such as heparin-induced thrombocytopenia, alternatives must be applied. The direct thrombin inhibitor bivalirudin has come forth as an attractive substitute. Bivalirudin is currently only approved for adult use in specific percutaneous coronary intervention settings. However, it has a growing off-label popularity in different contexts for both adult and pediatric patients. Experience with bivalirudin in children is mainly limited to extracorporeal membrane oxygenation, ventricular assist devices and during cardiopulmonary bypass surgery. Literature about its use as anticoagulation strategy for pediatric hemodialysis is very scarce. Here, we present two pediatric cases where bivalirudin was used during acute hemodialysis, followed by a short summary of recent literature.

Risk of venous thromboembolism after discontinuing prophylactic or therapeutic anticoagulation in patients with haematologic malignancies because of thrombocytopenia.

Although the rates of thrombocytopenia in patients with hematologic malignancies are well known, clinical reports of patients with haematological malignancies presenting with thrombocytopenia who developed venous thromboembolism (VTE) are rare. Defining the risk of VTE in patients with hematologic malignancies in whom anticoagulation is discontinued could help to individualize concepts of anticoagulation. We performed a retrospective analysis of medical records of patients with hematologic malignancies and thrombocytopenia grade 3 (25 × 109/L to < 50 × 109/L) or more severe in 2019-2022 in the Department of Haemato-Oncology at HELIOS Klinikum Krefeld. Data from 67 patients (34 (51%) males, 33 (49%) females) aged between 22 and 82 years (38 leukaemia, 23 lymphoma, 6 other) were included. Prophylactic anticoagulation was performed in 59 (88%) patients and therapeutic due to atrial fibrillation in 8 (12%). Anticoagulation was discontinued in 37 (55%) patients due to thrombocytopenia. Thrombotic events occurred in eight (12%) and minor bleeding in two (3%) patients. Seven patients developed a deep vein thrombosis (DVT) or superficial vein thrombosis (SVT) of the upper limbs, only one patient had a thrombosis of the femoral veins. Thrombotic event were much more frequent in patients suffering from leukaemia compared to lymphoma. Two thrombotic events occurred despite continued prophylaxis (2 of 30, 6.6%), the other six after discontinuing of anticoagulation (6 of 37, 16.2%). Both bleedings occurred in the group with continued anticoagulation. Five of the six patients with a thrombotic event, but without anticoagulation, received anticoagulation again despite a low platelet count and no bleeding was observed. Only one patient with jugular vein thrombosis and a platelet count around 4 × 109/L remained without anticoagulation and no thrombus formation was observed. Risk of VTE in our patients with haematologic malignancies in whom anticoagulation is discontinued due to thrombocytopenia grade 3 is about 2.5 times higher than in patients in whom anticoagulation is continued and predominantly affects patients with leukaemia and upper extremity.

Bivalirudin vs Heparin Anticoagulation in STEMI: Confirmation of the BRIGHT-4 Results.

BACKGROUND: In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myocardial infarction (STEMI). These findings require external validation. OBJECTIVES: This study sought to determine outcomes of bivalirudin vs heparin anticoagulation during PCI in STEMI. METHODS: We performed an individual-patient-data meta-analysis of all large randomized trials of bivalirudin vs heparin in STEMI patients undergoing primary PCI performed before BRIGHT-4. The primary endpoint was all-cause mortality. RESULTS: Six trials randomizing 15,254 patients were included. Pooled across all regimens of bivalirudin and glycoprotein IIb/IIIa inhibitor (GPI) use, bivalirudin reduced 30-day all-cause mortality (2.5% vs 2.9%; adjusted OR: 0.78; 95% CI: 0.62-0.99), cardiac mortality (adjusted OR: 0.69; 95% CI: 0.54-0.88), and major bleeding (adjusted OR: 0.53; 95% CI: 0.44-0.64) but increased reinfarction (adjusted OR: 1.30; 95% CI: 1.02-1.65) and stent thrombosis (adjusted OR: 1.43; 95% CI: 1.05-1.93) compared with heparin. In 4 trials in which 6,244 patients were randomized to bivalirudin plus a high-dose post-PCI infusion vs heparin without planned GPI use (the BRIGHT-4 regimens), 30-day all-cause mortality occurred in 1.8% vs 2.9% of patients, respectively (adjusted OR: 0.74; 95% CI: 0.48-1.12), and bivalirudin reduced cardiac mortality (adjusted OR: 0.62; 95% CI: 0.39-0.97) and major bleeding (adjusted OR: 0.49; 95% CI: 0.35-0.70), with similar rates of reinfarction (adjusted OR: 0.89; 95% CI: 0.58-1.38) and stent thrombosis (adjusted OR: 0.80; 95% CI: 0.41-1.57). CONCLUSIONS: In STEMI patients undergoing primary PCI, bivalirudin with a 2- to 4-hour post-PCI high-dose infusion reduced cardiac mortality and major bleeding without an increase in ischemic events compared with heparin monotherapy with provisional GPI use, confirming the BRIGHT-4 results.

The role of anticoagulation on the long-term survival of patients with pulmonary arterial hypertension: A meta-analysis of 15 cohort studies.

INTRODUCTION: Anticoagulation was once recommended for patients with pulmonary arterial hypertension (PAH). However, its survival benefit still remained controversial. We performed a meta-analysis to evaluate the effect of anticoagulation on the long-term survival of PAH patients. METHODS: The PubMed, EMBASE, Web of Science, and WanFang electronic database were searched for eligible studies. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated for effect estimate regarding anticoagulation on the survival of PAH patients. RESULTS: Fifteen cohort studies involving 4266 PAH patients were included. Approximately 45.8 % patients received anticoagulation. The mean follow-up period ranged from 2.1 to 14 years. Anticoagulation had a tendency to, however, did not significantly reduce mortality of PAH patients (HR: 0.86, 95 % CI: 0.73-1.02). In subgroup analysis, anticoagulation decreased the mortality risk as analyzed from retrospective studies (HR: 0.80, 95 % CI: 0.65-0.98), but not prospective studies (HR: 0.95, 95 % CI: 0.70-1.29). For both idiopathic PAH (IPAH) and connective tissue disease associated PAH (CTD-PAH), anticoagulation therapy did not significantly improve the long-term survival rate (HR: 0.83, 95 % CI: 0.65-1.07, and HR: 1.05, 95 % CI: 0.77-1.42, respectively), and this result remained unchanged when pooling data from either retrospective or prospective studies. Further analysis showed that anticoagulation had no advantage in reducing mortality in patients with systemic sclerosis associated PAH, systemic erythematosus lupus related PAH (free of antiphospholipid syndrome), or CTD-PAH of non-specified etiology. CONCLUSION: Anticoagulation may not reduce the long-term mortality of PAH patients, including those with IPAH and CTD-PAH. In the management of PAH, anticoagulants should be prescribed with caution before comprehensive risk to benefit evaluation. Larger and more vigorously designed controlled trials are warranted.

COVID-19 venous thromboembolism prophylaxis guidelines in pediatrics.

INTRODUCTION: SARS-CoV-2 (COVID-19) infection and multisystem inflammatory syndrome in children (MIS-C) are risk factors for venous thromboembolism (VTE). Guidelines for VTE prophylaxis were established at our institution at the beginning of the pandemic. Patients who had any VTE risk factors in addition to COVID-19 met criteria for anticoagulation prophylaxis. Patients who were diagnosed with MIS-C met criteria regardless of additional risk factors. MATERIALS AND METHODS: We conducted a retrospective review of patients admitted with COVID-19 or MIS-C to determine compliance with VTE prophylaxis guidelines and to evaluate the incidence of VTE and bleeding events in our population. RESULTS AND CONCLUSIONS: Among a total of 678 patients admitted with COVID-19 or MIS-C, 519 (76 %) patients met criteria for VTE prophylaxis and 348 (65.6 %) started prophylaxis. Logistic regression analysis identified a personal or family history of thrombosis or thrombophilia, diagnosis of MIS-C, admission to the intensive care unit, and presence of a central venous catheter as significantly associated with starting VTE prophylaxis. There were 18 patients who developed VTE. Minor bleeding events occurred in 19 patients (5 %), patient important bleeding, no intervention occurred in 8 patients (2 %), clinically relevant nonmajor bleeding in 8 patients (2 %), and major bleeding in 10 patients (3 %). The incidence of VTE in our patients with COVID-19 and MIS-C is similar to VTE rates at other institutions. We found that universally recognized VTE risk factors were appropriate to include as risk factors for thrombosis in hospitalized children with COVID-19 and MIS-C.

A Mobile Application for Anticoagulation Management in Patients After Heart Valve Replacement: A Usability Study.

Purpose: Individualized anticoagulation therapy is a major challenge for patients after heart valve replacement. Mobile applications assisted by Artificial intelligence (AI) have great potential to meet the individual needs of patients. The study aimed to develop an AI technology-assisted mobile application (app) for anticoagulation management, understand patients' acceptance of such applications, and determine its feasibility. Methods: After using the mobile application for anticoagulation management for 2 weeks, patients, doctors, and nurses rated its usability using the System Usability Scale (SUS). Additionally, semi-structured interviews were conducted with some patients, doctors, and nurses to gain insights about their thoughts and suggestions regarding the procedure. Results: The study comprised 80 participants, including 38 patients, 18 doctors, and 24 nurses. The average SUS score for patients was 82.37±5.45; for doctors, it was 84.17±5.82; and for nurses, it was 81.88±6.44. This means the patients, physicians, and nurses rated the app highly usable. Semi-structured interviews were conducted on the app's usability with 18 participants (six nurses, three physicians, and nine patients). The interview results revealed that patients found the application of anticoagulation management simple and convenient, with high expectations for a precise dosage recommendation of anticoagulant drugs. Some patients expressed concerns regarding personal information security. Both doctors and nurses believed that elderly patients needed assistance from young family members to use the app and that it could improve patients' anticoagulant self-management ability. Some nurses also mentioned that the use of the app brought great convenience for transitional care. Conclusion: This study confirmed the feasibility of using an AI technology-assisted mobile application for anticoagulation management in patients after heart valve replacement. To further develop this application, challenges lie in continuously improving the accuracy of recommended drug doses, obtaining family support, and ensuring information security.

Management and Outcomes of Pulmonary Embolism in the Oldest-Old.

Background: Treatment for pulmonary embolism has expanded to include Direct Oral Anticoagulants (DOACs). The incidence of pulmonary-embolism (PE) in "oldest-old" age group (≥85 years) is rapidly increasing, but there is limited research on its management and clinical outcomes. Aim: To examine the differences in management and outcomes in those aged ≥85 years compared to other age groups. Methods: We performed a retrospective cohort-study of 373 consecutive patients with pulmonary embolism confirmed on imaging by Computed Tomography Pulmonary Angiogram (CTPA) or Ventilation Perfusion (VQ) Scan at a principal referral hospital in Sydney, Australia. Data collected include clinical and demographic data, Charlson comorbidity index, treatment type and outcomes including complications, recurrent venous thromboembolism, and mortality. Results: Across the age groups, DOACS were prescribed to 53.4% (n=199) of patients. In oldest-old patients with PE, LMWH bridging to warfarin was the most frequently prescribed treatment, used in 46.2% (n=18, 95% CI: 30.8%-61.5%, p=0.003) of these patients. The mortality rate for patients on LMWH was 13.9% (n=5, 95% CI: 4.2%-37.5%, p=0.553). Overall, major bleeding incidents were rare, occurring in just 1.7% (n=4, 95% CI: 0.4%-3.3%) of patients, with no significant differences in outcomes across age groups. Conclusion: DOACs are increasingly used as the treatment modality of choice in atrial fibrillation but are less well studied in pulmonary embolism, particularly in oldest-old patients. We found that the safety and efficacy profile of DOACs in pulmonary embolism treatment is similar across the age groups. Our study does not support any change in treatment protocols of PE in the oldest old, but further studies are required to confirm our findings.

Prospective study on the impact of different anti-thrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter aortic valves - The NOTION-4 trial: Anti-thrombotic therapy and TAV-HALT.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard-of-care treatment for a majority of patients with severe, symptomatic aortic stenosis. The post-procedural anti-thrombotic therapeutic management is still a topic of debate and could affect the incidence of HALT, a phenomenon which can be assessed by four-dimensional computed tomography (4DCT). TRIAL DESIGN: The NOTION-4 trial is a randomized controlled trial comprising TAVR patients with no indication for oral anticoagulant (OAC) therapy, comparing lifelong single anti-platelet therapy (standard arm) versus early 3-month direct oral anticoagulant (DOAC) therapy followed by single anti-plateletet therapy (experimental arm). The incidence of HALT and clinical endpoints will be evaluated in both groups at 3 months, 1 year and 5 years after randomization. The primary endpoint is the number of patients with at least one bioprosthetic aortic valve leaflet with HALT as assessed by cardiac 4DCT imaging at 1 year. The trial is powered for superiority testing and started enrollment in 2021. In total, 324 patients will be included. The last patient is expected to be enrolled by the end of 2024 and the primary endpoint is to be presented in 2026. CONCLUSION AND PERSPECTIVE: The NOTION-4 trial aims to study whether an early 3-month DOAC therapy after TAVR can result in a sustained lower incidence of HALT in transcatheter aortic valves. This trial holds the potential to give valuable insights into whether early OAC therapy should be integrated in future guidelines for post-TAVR anti-thrombotic therapeutic management. TRIAL REGISTRATION: NOTION-4, ClinicalTrials.gov ID NCT06449469, https://clinicaltrials.gov/study/NCT06449469.

A safety comparison of heparin and argatroban anticoagulation in veno-venous extracorporeal membrane oxygenation with a focus on bleeding.

BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. STUDY DESIGN AND METHODS: An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. RESULTS: The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). DISCUSSION: Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.