Subclinical leaflet thrombosis (SLT) can be one of the causes of transcatheter heart valve (THV) failure after transcatheter aortic valve implantation (TAVI). We sought to clarify the formation process of SLT and thrombogenicity during the perioperative period of TAVI. This multicenter, prospective, single-arm interventional study enrolled 26 patients treated with edoxaban for atrial fibrillation and who underwent TAVI for severe aortic stenosis between September 2018 and September 2022. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI in 18 patients and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD) (n = 11). SLT was observed in 16.7% (3/18) at 1 week, but decreased to 5.9% (1/17) at 3 months after TAVI. Patients with SLT at 1 week had a significantly decreased maximal leaflet thickness compared to those without SLT. Thrombogenicity assessed by T-TAS decreased markedly at 1 week and tended to increase at 3 months. The stagnation volume assessed by CFD was positively associated with a higher maximum leaflet thickness. This study showed the course of leaflet thrombus formation and visualization of stagnation in neo-sinus of THV in the acute phase after TAVI.

OBJECTIVE: Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT.
METHODS: After IRB approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. Demographic and clinical variables were collected: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes.
RESULTS: 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either non-cardiac, non-vascular surgery or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing) and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K (+/- 104.6K) within an average of 2.3 days and 364K (+/- 273.9K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days.
CONCLUSIONS: Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.

BACKGROUND: Venous thromboembolism (VTE) is a widespread and significant cause of morbidity and mortality on a global scale. The primary objective of this cross-sectional study is to examine the impact of anticoagulant therapy on major organ hemorrhage events in patients diagnosed with acute venous thromboembolism (VTE). Specifically, this research compares the effects of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs).
METHODS: This retrospective observational study examined the medical records of 46 patients who had been diagnosed with VTE and were receiving treatment with DOACs or VKAs. The documentation of patient characteristics encompassed demographic information, comorbidities, and treatment particulars. Within 30 days of hospital admission, the incidence of significant organ bleeding events, with an emphasis on gastrointestinal and intracranial hemorrhage, was the primary outcome evaluated.
RESULTS: Overall, 46 patients with VTE who were treated with oral anticoagulation therapy participated in the study. Twenty-four and 22 patients were administered VKAs and DOACs, respectively. The similarity in baseline characteristics between the DOAC and VKA groups ensured that the analyses were well-matched. The examination of bleeding sites unveiled subtle variations, as the DOAC group exhibited a progressive increase in the incidence of intracranial bleeding (12, 55.5%), while the VKA group demonstrated a surge in upper gastrointestinal bleeding (12, 50%) as well. While lacking statistical significance, these observed patterns are consistent with prior research that indicates that DOACs may have a lower risk of catastrophic hemorrhage in comparison to VKAs. The overall in-hospital mortality rate for patients treated with VKA was 33.3% (n=8), while that treated with DOAC was 18.2% (n=4). These differences did not reach statistical significance (P>0.05). In a similar vein, the evaluation of mortality associated with hemorrhage revealed six (25%) in the group receiving VKA and three (13.6%) in the group receiving DOAC; the P value was not statistically significant (P>0.05).
CONCLUSIONS: This study contributes valuable insights into bleeding outcomes associated with anticoagulant therapy for acute VTE. The nuanced differences in bleeding patterns highlight the complexity of anticoagulant selection, emphasizing the importance of considering bleeding site considerations. The comparable mortality rates support existing evidence regarding the favorable safety profile of DOACs.

Atrial fibrillation (AF) carries a stroke risk, often necessitating anticoagulation, especially in patients with risk factors. With the advent of implantable and wearable heart monitors, episodes of short bouts of atrial arrhythmias called atrial high-rate episodes (AHREs) or subclinical AF (SCAF) are commonly identified. The necessity of anticoagulation in patients with SCAF is unclear. However, recent randomized controlled trials, the NOAH-AFNET 6 and ARTESIA, have offered insights into this matter. Furthermore, a study-level meta-analysis combining data from both these trials has provided more detailed information. Reviewing the information thus far, we can conclude that DOACs can result in a notable reduction in the risk of ischemic stroke and can potentially decrease the risk of debilitating stroke, albeit with an increased risk of major bleeding. Thus, informed, shared decision-making is essential, weighing the potential benefits of stroke prevention against the risk of major bleeding when considering anticoagulation in this patient population.

OBJECTIVE: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analyzed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety.
METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs versus VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effect model meta-analysis, and their robustness was investigated using sensitivity and influential analyses.
RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3,587 patients (2,489 VKA vs. 1,098 DOAC therapy). The pooled estimates for stroke or systemic embolism (OR 0.81; 95% CI [0.57, 1.15]) and thrombus resolution (OR 1.12; 95% CI [0.86; 1.46]) were comparable, and there was low heterogeneity overall across the included studies. DOAC use was associated with lower odds of all-cause death (OR 0.65; 95%CI [0.46; 0.92]) and a composite bleeding endpoint (OR 0.67; 95%CI [0.47; 0.97]). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots.
CONCLUSIONS: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution compared to VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.

Contrary to direct oral anticoagulants (DOAC), unfractionated heparin (UFH) requires daily monitoring when administered at therapeutic dose. At present, UFH monitoring is preferably carried out by measuring plasma anti-Xa activity, however, in patients previously treated with an anti-Xa DOAC and switched to UFH, there is a high risk of DOAC interfering with the measurement of UFH anti-Xa activity. Residual anti-Xa DOAC in the sample can lead to an overestimation of the anticoagulant activity attributed to heparin and thus to incorrect anticoagulation. This risk of interference should not be overlooked because interference may occur even at concentration of DOAC below the hemostatic safety threshold and can last several days. To overcome this issue, several alternatives are being studied. This note provides an update on anti-Xa DOAC interference and different strategies available in current practice. It also underlines the importance of communication between biologists and clinicians on anticoagulant treatments received by patients.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

BACKGROUND: The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.
METHODS: This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.
RESULTS: Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0-11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0-5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.
CONCLUSIONS: Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients\' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement.

Hip fractures are an increasingly common injury in the senior population and almost always require surgical fixation or prosthetic replacement. These surgeries, according to the American Academy of Orthopaedic Surgeons, are considered high-risk for bleeding, especially in a population fraught with comorbidities and often presenting on anticoagulation medications. Direct oral anticoagulants represent a class of drugs that have been becoming more popular in use in this population, with many benefits over the historically used Warfarin. There are recommendations for preoperative discontinuation and postoperative resumption of these medications, which can be more readily managed for elective surgeries. However, there is a paucity of literature detailing best practice guidelines for the perioperative management of direct oral anticoagulants when a patient presents with a hip fracture. This review article summary of the periprocedural management of DOACs for hip surgery was developed by examining the American College of Chest Physicians evidence-based clinical practice guidelines, Perioperative Guidelines on Antiplatelet and Anticoagulant Agents written by anesthesiologists, various retrospective studies, and drug labels for pharmacokinetic data. These recommendations should be used as a guideline, along with the collaboration of multidisciplinary hospital teams during inpatient admission, to manage these complex patients.