Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Cerebral Venous Sinus Thrombosis After Lumbar Epidural Steroid Injection: A Case Report.

Cerebral venous sinus thrombosis (CVST) is an exceedingly rare complication of epidural anesthesia, with only a handful of known cases after epidural steroid injection (ESI). We report a case of CVST in a 33-year-old male patient that presented with headache after lumbar ESI. His clinical status initially improved on anticoagulation in the intensive care unit. However, he had a sudden worsening of cerebral edema that required an emergent hemicraniectomy. Ultimately, the patient was pronounced dead by neurologic criteria. This case highlights the importance of keeping this rare but potentially fatal diagnosis in the differential even in lower-risk patient populations.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

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.

Poor patients' knowledge about venous thromboembolism and its therapy is associated with increased risk of major bleeding and discontinuation of anticoagulation: A cohort study.

It has been shown that patients' knowledge about venous thromboembolism (VTE) and its therapy is suboptimal, which might reduce compliance and worsen prognosis. We investigated whether low VTE patients' knowledge affects their clinical outcomes during long-term follow-up. We evaluated 151 consecutive patients (51.8 ±â€…15.7 years) after unprovoked VTE, who were recruited from the outpatient clinic (Krakow, Poland). All patients received anticoagulant treatment, mostly with direct oral anticoagulants (n = 113, 74.8%). The modified Jessa Atrial fibrillation Knowledge Questionnaire (JAKQ-VTE; 16 questions) was used to assess the knowledge of VTE and anticoagulant therapy. During a median follow-up of 58.0 months, VTE recurrence, major bleeding, and anticoagulation withdrawal were recorded. The median percentage of correct responses was 62.5% (12.5-100%) and was inversely correlated with age (P < .01). Diabetic patients and those with positive family history of VTE had lower overall scoring compared to the remainder (both P < .05). Major bleeding (n = 10, 6.6%) and anticoagulation withdrawal (n = 28, 18.5%), but not VTE recurrence (n = 12, 7.9%), were associated with lower overall scoring compared to the remainder (48.8% ±â€…12.5% vs 63.8% ±â€…16.3%, P = .003 and 55.3% ±â€…14.7% vs 64.4% ±â€…16.3%, P = .040, respectively). Major bleeding was independently associated with the female sex (hazard ratio [HR] 6.18; 95% confidence interval [CI] 1.15-33.19, P = .034), younger age (HR per 10 years 0.55; 95% CI 0.34-0.90, P = .016), OAC therapy discontinuation (HR 6.69; 95% CI 1.62-27.70), and lower overall scoring of JAKQ-VTE (HR 0.60 per 10 percentage points; 95% CI 0.40-0.92, P = .019). Insufficient knowledge about VTE and anticoagulant treatment predisposes to a higher risk of major bleeding and therapy discontinuation, but not VTE recurrence in unprovoked VTE patients during long-term follow-up.

[Heparin Resistance After Administration of Andexanet Alfa:Report of a Case].

The management of patients on direct oral anticoagulants (DOACs) who require an emergency cardiac surgery has been disputed in Japan. Recently, the use of andexanet alfa as an antidote for apixaban and rivaroxaban, is approved in the setting of life-threating or uncontrollable major bleeding. However, the efficacy and safety of andexanet alfa have been investigated. We report a case of 72-year-old man taking rivaroxaban who required the emergency coronary artery bypass grafting. He received andexanet alfa prior to the operation. Heparin resistance was noted before starting cardiopulmonary bypass. Consideration should be given to the use of andexanet alfa before or during cardiopulmonary bypass.

Duration of triple antithrombotic therapy and clinical outcomes after percutaneous coronary intervention in atrial fibrillation.

BACKGROUND: Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. RESEARCH DESIGN AND METHODS: A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. RESULTS: Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). CONCLUSIONS: TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.

Effectiveness and safety of continuous low-molecular-weight heparin versus switching to direct oral anticoagulants in cancer-associated venous thrombosis.

Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.

Thrombotic and Hemorrhagic Outcomes After Elective Surgery in Preoperatively Anticoagulated Patients.

OBJECTIVE: To better understand the incidence and timing of thrombotic and hemorrhagic complications in anticoagulated patients undergoing elective surgery. METHODS: Using institutional American College of Surgeons National Surgical Quality Improvement Program data, we identified patients receiving preoperative anticoagulation undergoing elective surgery between 2011 and 2021. Medical records review supplemented National Surgical Quality Improvement Program data to detail complication and anticoagulation type and timing. Outcomes for postoperative hemorrhage, acute venous thromboembolism (VTE), and cerebrovascular accident (CVA) were collected. RESULTS: A total of 1442 patients met inclusion criteria, and 84 patients (5.8%) experienced 1 or more complications. There were 4 CVA (0.3%), 16 VTE (1.1%), and 68 bleeding (4.7%) events postoperatively. Three patients (75%) with CVA, 10 patients (62.5%) with VTE, and 18 patients (26.5%) with postoperative bleeding had resumed therapeutic anticoagulation before the complication. In terms of long-term sequelae in the CVA cohort, there was 1 mortality (25%), and an additional patient (25%) continues to experience long-term physical and mild cognitive impairments. Patients who experienced postoperative VTE required only anticoagulation adjustments. In patients who experienced bleeding complications, 6 (8.8%) required intensive care unit admissions, and there was 1 mortality (1.5%). CONCLUSION: Despite the increased use of anticoagulation over time, balancing postoperative bleeding and thrombotic risks remains challenging. Bleeding complications were most common in preoperatively anticoagulated patients undergoing elective surgery. Earlier postoperative resumption of anticoagulation is unlikely to prevent thrombotic events as 65% of patients had already resumed therapeutic anticoagulation.

Building evidence on safety of endovascular thrombectomy for patients under anticoagulation with vitamin K antagonists.

A recent study by Brian Mac Grory and colleagues investigated the safety of endovascular thrombectomy (EVT) among patients under vitamin K antagonists (VKAs) use within 7 days prior to hospital admission. Through this retrospective, observational cohort study, they found prior VKA use did not increase the risk of symptomatic intracranial hemorrhage (sICH) overall. However, recent VKA use with a presenting international normalized ratio (INR) > 1.7 was associated with a significantly increased risk of sICH. Future large-scale randomized controlled trials should be conducted to further clarify the effects and feasibility of EVT therapy in ischemic stroke patients under anticoagulation.

Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

BACKGROUND: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. METHODS: A systematic review and meta-analysis was performed. RESULTS: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%). CONCLUSION: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

Management of Extracorporeal Membrane Oxygenation Anticoagulation in the Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Four good practice statements, 7 recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.

Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: The management of bleeding and thrombotic complications of ECMO. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.

Warfarin-related nephropathy: unveiling the hidden dangers of anticoagulation.

Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical prosthetic valves require long-term anticoagulant therapy. Nonetheless, warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical prosthetic valves constitute a special group among the entire anticoagulant population. The present study recorded two cases of patients who had undergone mechanical prosthetic valve surgery and were receiving warfarin therapy. They presented to the hospital with gross hematuria and progressive creatinine levels. Notably, their international normalized ratio (INR) did not exceed three. Subsequent renal biopsies confirmed WRN with IgA nephropathy. The two patients continued to receive warfarin as anticoagulation therapy and were prescribed oral corticosteroids and cyclophosphamide, which resulted in improved renal function during the follow-up. Based on a review of all relevant literature and the present study, we proposed a new challenge: must elevated INR levels be one of the criteria for clinical diagnosis of WRN? Perhaps some inspiration can be drawn from the present article.