Background and Objectives: Hip surgery is increasingly performed among elderly patients. Oral antithrombotics, which are taken for patients' underlying diseases, are a main concern regarding perioperative bleeding. Postoperative venous thromboembolism (VTE) is a leading cause of mortality after hip surgery. Therefore, administration of preoperative oral antithrombotics is a double-edged sword in hip surgery. In this study, we examined the correlation between the occurrence of postoperative VTE and the type of oral antithrombotics administered preoperatively. Materials and Methods: We analyzed the medical records of 601 patients aged 19 and over who underwent hip surgery from January 2021 to June 2023. The patients were assigned to two groups as follows: Groups VTE+ (patients who developed postoperative VTE) and VTE- (patients who did not develop postoperative VTE), respectively. Results: Of the 139 patients who had been taking oral antithrombotics for 6 months or more, 24 were allocated to group VTE+ and 115 to group VTE-, respectively. The number of patients who took clopidogrel and cilostazol was significantly higher in groups VTE- and VTE+, respectively (12.5 vs. 33.9%, p = 0.038, odds ratio (OR) = 0.278, 95% confidence interval (CI) = 0.078-0.991; 20.8 vs. 5.2%, p = 0.010, 95% CI = 1.325-17.245; group VTE+ vs. group VTE-). Preoperative albumin levels were significantly lower in group VTE+ (3.4 ± 0.6 g/dL vs. 3.7 ± 0.4 g/dL, p = 0.004, OR = 0.285, 95% CI = 0.115-0.702). In multivariate regression analysis, the results were statistically significant for clopidogrel, cilostazol, and preoperative albumin levels (p = 0.035, OR = 0.237, 95% CI = 0.062-0.901; p = 0.011, OR = 6.479, 95% CI = 1.542-27.226; p = 0.002, OR = 0.211, 95% CI = 0.080-0.558). Conclusions: Among the patients who had been taking oral antithrombotics for ≥6 months, clopidogrel had a prophylactic effect, but cilostazol showed an aggravating effect on postoperative VTE in hip surgery. Preoperative hypoalbuminemia increases the risk of postoperative VTE in hip surgery.

Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease.Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry. Prevalent VKA users diagnosed with a pre-specified life-limiting disease between January 1, 2013 and December 31, 2019 were included and followed until December 31, 2019. Bleeding and thromboembolic events were identified by hospitalization data. Cumulative incidences of anticoagulant discontinuation, accounting for death as competing risk, and event rates for both anticoagulant exposed and unexposed person-years (PYs) were determined.Among 18,145 VKA users (median age 81 years [IQR: 74-86], 49% females, median survival time 2.03 years [95%CI: 1.97-2.10]), the most common life-limiting diseases were heart disease (60.0%), hip fracture (18.1%), and cancer (13.5%). One year after diagnosis, the cumulative incidence of anticoagulant discontinuation was 14.0% (95%CI: 13.5-14.6). Over 80% of patients continued anticoagulant therapy until the last month before death, with median 14 days between discontinuation and death. Event rates per 100 PYs (95%CI) were comparable during anticoagulant use and after discontinuation for bleeding 2.6 (2.4-2.8) versus 2.1 (1.5-2.8), venous thromboembolism 0.2 (0.1-0.2) versus 0.4 (0.2-0.7), and arterial thromboembolism 3.1 (2.9-3.3) versus 3.3 (2.6-4.2).Most VKA users with a life-limiting disease continued anticoagulant treatment during their last phase of life, with similar rates of bleeding and thromboembolic events during use and after discontinuation.

Apixaban is increasingly used instead of vitamin K antagonists (VKAs) for long-term anticoagulation during HeartMate 3 (HM3) support. However, data on its pharmacokinetics in this context is lacking. We present real-world data on apixaban levels and outcomes in adult and pediatric HM3 patients, and evaluate our dosing strategy based on plasma sampling.

Since June-2023, all new HM3 recipients were initiated on apixaban. Additionally, hospitalized adult HM3 patients were transitioned from VKA to apixaban. Trough apixaban levels were measured in all patients, and dose adjustment was considered to exceed 50ng/ml.

This retrospective study includes 34 HM3 patients, 4 pediatric (all primary use) and 30 adult patients (16 primary use). In primary use, apixaban was started at median of 14 (interquartile range [IQR]: 11-16, pediatric) and 11 (IQR: 6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3,191 patient-days. Six minor bleeding events occurred (0.69 events per patient-year), mostly (67%) during dual therapy with aspirin. Fourteen patients had dose adjustment; median trough and peak levels on final dosage were 73 (IQR: 50-92) and 179 (IQR: 133-242) ng/ml in the pediatric group and 109 (IQR: 83-144) and 176 (IQR: 134-228) ng/ml in the adult cohort, respectively. Inter- and intraindividual variation in apixaban peak levels was considerable, while trough levels showed less variability.

With a dosing strategy to target trough apixaban levels of >50ng/ml, there were no thrombotic events during a follow-up of 3,191 patient-days (of which 820 patient-days in children). We observed no major, and only few non-major bleeds, mainly in patients concomitantly taking aspirin.

Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available anticoagulants entail an increased risk of bleeding, which detrimentally impacts on prognosis and hinders the administration of an effective antithrombotic regimen. Factor XI (FXI) inhibition has emerged as a strategy to uncouple prevention of thrombosis from bleeding. Indeed, while FXI is crucial for the amplification phase in pathological thrombosis, it is ancillary in physiological hemostasis. A comprehensive search in several scientific databases has been performed to identify relevant studies in the field. In addition, ongoing trials have been searched for in proper datasets to provide an updated and comprehensive assessment of the current state of investigations on FXI inhibition. Many compounds have been tested to inhibit FXI at different stages (i.e., synthesis, activation, or interactions with target molecules and coagulation factors). These include antisense oligonucleotides, monoclonal antibodies, small molecules, natural peptides and aptamers. In phase 2 studies, FXI inhibitors reduced thrombotic complications without any corresponding increase in bleeding. FXI inhibitors were noninferior and potentially superior to low-molecular-weight heparin in orthopedic surgery and reduced bleeding compared to apixaban in patients with atrial fibrillation. FXI inhibition is also under testing in other conditions, including end-stage renal disease, cancer, or noncardioembolic stroke. FXI inhibition represents a promising and rapidly emerging approach for a number of clinical indications. This article reviews the rationale, evidence, pharmacology, and future applications of FXI inhibition.

The introduction of evidence-based and structured guidelines has undoubtedly improved the care of cardiologic patients and in many cases simplified decision-making for the treatment team. The European Society of Cardiology in collaboration with the European Association for Cardio-Thoracic Surgery, the American College of Cardiology, the American Heart Association, the American College of Clinical Pharmacy, and the Heart Rhythm Society, and the Canadian Cardiovascular Society/Canadian Heart Rhythm Society have developed guidelines for the management of patients with atrial fibrillation. Because all 3 guidelines refer to almost the same scientific data, their recommendations are undoubtedly largely in agreement. Nevertheless, there are some interesting differences based on different interpretations of the same study, different publication dates, or differences in local conditions and health care resources. The following article aims at lining out these similarities and differences.

Arterial and venous thromboses are the leading causes of morbidity and mortality worldwide. Numerous antithrombotic agents are currently available with antiplatelet, thrombolytic/fibrinolytic, and anticoagulant activity. However, all the currently available antithrombotic agents carry a risk of bleeding that often prevents their use. This unfavorable risk-benefit profile is particularly challenging for patients with cancer-associated venous thromboembolism, patients with atrial fibrillation at a high risk of bleeding, and patients with end-stage renal disease. Patients with ischemic stroke and acute coronary syndromes have not yet found a favorable risk-benefit profile with anticoagulant therapy to help reduce the residual thromboembolic risk that remains after antiplatelet and lipid therapy. Two emerging classes of antithrombotic agents, factor (F)XI or activated factor Ⅺ (FⅪa) inhibitors and glycoprotein VI inhibitors, have shown promise in their ability to prevent pathologic thrombosis without increasing the risk of hemostatic-related bleeding in phase 2 studies. Among the FⅪ/FXIa inhibitors of coagulation, a parenterally administered monoclonal antibody (abelacimab) and 2 orally administered small molecule inhibitors (asundexian, milvexian) are collectively being studied in patients with atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke. One parenterally administered glycoprotein VI antiplatelet agent (glenzocimab) is currently being studied in patients with ischemic stroke. If shown to be efficacious and safe in ongoing phase 3 studies, both classes of emerging antithrombotic agents have the potential to greatly improve outcomes for patients with challenging thrombotic conditions.

Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) for stroke prevention in many patients with atrial fibrillation, but VKAs may still be preferred in some situations. We use a case-based approach to present the evidence for the possible use of a VKA in preference to a DOAC in patients with atrial fibrillation and rheumatic mitral stenosis, high body mass index, frailty, and breakthrough stroke despite being prescribed a DOAC.

The administration of blood components and their alternatives can be lifesaving. Anaemia, bleeding and transfusion are all associated with poor peri-operative outcomes. Considerable changes in the approaches to optimal use of blood components and their alternatives, driven by the findings of large randomised controlled trials and improved haemovigilance, have become apparent over the past decade. The aim of these updated guidelines is to provide an evidence-based set of recommendations so that anaesthetists and peri-operative physicians might provide high-quality care.

An expert multidisciplinary, multi-society working party conducted targeted literature reviews, followed by a three-round Delphi process to produce these guidelines.

We agreed on 12 key recommendations. Overall, these highlight the importance of organisational factors for safe transfusion and timely provision of blood components; the need for protocols that are targeted to different clinical contexts of major bleeding; and strategies to avoid the need for transfusion, minimise bleeding and manage anticoagulant therapy.

All anaesthetists involved in the care of patients at risk of major bleeding and peri-operative transfusion should be aware of the treatment options and approaches that are available to them. These contemporary guidelines aim to provide recommendations across a range of clinical situations.

As the life expectancy of individuals with hemophilia continues to increase, the complexity of balancing bleeding risks and thrombotic management has become increasingly critical in people with hemophilia with or at a high risk of thrombosis. Advances in hemophilia therapies such as extended half-life coagulation factors, non-factor therapies, rebalancing agents, and gene therapy have expanded treatment options for a variety of people with hemophilia. The thrombotic risk of people with hemophilia in general are relatively low as compared to those without hemophilia. However, antithrombotic therapy for prevention and treatment for thrombosis should still be considered in some situations, even in hemophilia. This clinical focus highlights the use of antithrombotic therapy in the management of thrombosis in people with hemophilia. A multidisciplinary, personalized approach is essential for optimizing the safety and efficacy of antithrombotic therapy in people with hemophilia with or at a high risk of thrombosis. High performance computer based multidimensional data analysis may help in establishing the personalized antithrombotic therapy in the future.

Bleeding is the most common side effect during treatment with vitamin K antagonists (VKAs). Sometimes, VKA use causes bleeding episodes due to rare variants in the factor IX (FIX) propeptide that modify the affinity of FIX propeptide to the binding of γ-glutamyl carboxylase. We report on a 51-year-old patient who presented with recurrent spontaneous and severe intramuscular and cutaneous bleedings during VKA (warfarin) treatment for the presence of a prosthetic mechanical aortic valve. Laboratory evaluation revealed INR within the therapeutic range with markedly prolonged aPTT and a large reduction of FIX levels. Laboratory parameters significantly improved when warfarin was switched with low-molecular-weight heparin. Next-generation sequencing analysis revealed the variant p.(Ala37Thr) in the F9 gene, which has been previously associated with VKA sensitivity. As an alternative to warfarin, apixaban 5 mg twice daily and aspirin 100 mg daily were started, with no thrombosis or recurrence of hemorrhage and normalization of INR, aPTT, and FIX levels, at 12-month follow-up. We also performed a literature search across PubMed and Scopus, until January 2025. The analysis evidenced five case reports and two case series. The mechanisms of this rare VKA hypersensitivity have also been reviewed. In conclusion, while VKA hypersensitivity is a rare phenomenon, awareness of this complication and the current accessibility to molecular testing make it important to identify patients at risk. The efficacy/safety of direct thrombin or factor Xa inhibitors in patients with a mechanical heart valve and VKA hypersensitivity due to the F9 p.(Ala37Thr) variant deserves more attention and further investigation.

Advances in alternative oral anticoagulants has reduced use and clinician comfort with warfarin. Our specialty anticoagulation clinic (AC) operates at maximum capacity and must transfer patients to accept new referrals.

To compare time within therapeutic range (TTR) during 6 months of AC care versus following transfer to primary care for a minimum of 6 months and to a maximum of 24 months. Secondarily, to compare frequency of INR assessments, proportion of INRs ≤1.5 and > 5, and rates of bleeding and thromboembolic events post-transfer to primary care.

Mixed retrospective chart review and administrative audit with a before-after study design for patients managed by the University of Alberta's AC for at least 6 months that were transferred to primary care.

177 (27.7 %) patients were included, managed by the AC for 3.4 years (1.3, 7.9). TTR declined during the first 6 months post-transfer with AC care achieving 69.2 % and primary care 64.5 % (p = 0.02) and when compared to the 24-month interval (69.2 % vs 63.4 %; respectively; p = 0.003). A shorter interval between INRs in AC care was observed (28.9 (24.4) vs 34.5 (31.7) days, respectively; p = 0.0004). Similar numbers of critical INRs occurred between groups, whereas more INRs ≤1.5 occurred in primary care (7.3 % vs 4.7 %, respectively; p = 0.0003). Bleeding and thromboembolic event rates were balanced following transfer to primary care with both occurring at 9.4 % per patient year.

A decline in anticoagulation control after transfer to primary care was observed, which appeared to be driven by a greater proportion of subtherapeutic INRs.

There is an unmet need for high-quality data from prospective studies on the safety and effectiveness of direct oral anticoagulants (DOACs) for the treatment of cerebral venous thrombosis (CVT). We aimed to compare the safety and effectiveness of DOACs versus vitamin K antagonists (VKAs) for the treatment of CVT in a setting that reflects daily clinical practice.

DOAC-CVT was an international, prospective, observational cohort study done in 65 hospitals in 23 countries across five continents. Eligible patients were adults (aged ≥18 years) with radiologically confirmed CVT starting oral anticoagulant treatment with either DOACs or VKAs, as per local practice, within 30 days after diagnosis. Exclusion criteria were previous use of anticoagulants at the time of CVT diagnosis or an absolute contraindication to DOACs (eg, pregnancy and lactation, or severe renal or liver disease). Data were collected during routine clinical visits or telephone consultations at CVT diagnosis (baseline) and at 3 months, 6 months, and 12 months after CVT diagnosis. The primary endpoint was a composite of symptomatic venous thromboembolism and major bleeding events (International Society on Thrombosis and Haemostasis criteria) at 6 months. Main outcomes were adjusted for the confounders age, renal function, active cancer, CNS infections, concomitant antiplatelet use, country of inclusion's income status, Glasgow Coma Scale score, intracranial haemorrhage, antiphospholipid antibodies, previous major bleeding, and previous venous thromboembolism using inverse probability-of-treatment weighting. This study is registered at ClinicalTrials.gov (NCT04660747) and is ongoing.

Between Jan 27, 2021, and Jan 15, 2024, 619 patients were included; 401 (65%) patients started DOAC treatment, and 218 (35%) patients started VKA treatment. 390 (63%) of 619 patients were female and 229 (37%) of 619 patients were male. Patients' median age was 41 years (IQR 28-51). 6-month follow-up data were available for 617 (>99%) of 619 patients. 12 (3%) of 401 patients in the DOAC group and seven (3%) of 218 patients in the VKA group had a primary outcome event (weighted odds ratio [OR] 0·99 [95% CI 0·37-3·38]). Three (1%) of 401 patients in the DOAC group died versus three (1%) of 218 patients in the VKA group (weighted OR 0·55 [95% CI 0·11-2·80]).

The rate of recurrent thrombosis and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. This study adds to the increasing evidence that DOACs are a reasonable treatment option for CVT alongside VKAs.

Netherlands Thrombosis Foundation.

Taking a historical perspective, we review the discovery, pharmacology, and clinical evaluation of the old and new anticoagulants that have been approved for clinical use. The drugs are discussed chronologically, starting in the 1880s, and progressing through to 2024. The innovations in technology used to develop novel anticoagulants came in fits and starts and reflected the advances in science and technology over these decades, whereas the shift from anecdote to evidence-based use of anticoagulants was delayed until the principles of epidemiology and biostatistics were introduced into clinical trial design and to the approval process. Hirudin, heparin, and vitamin K antagonists were discovered by chance, and were used clinically before their mechanism of action was elucidated and before their net clinical benefits were evaluated in randomized clinical trials. Subsequent anticoagulants were designed based on a better understanding of the structure and function of coagulation proteins, including antithrombin, thrombin, and factor Xa, and underwent more rigorous preclinical and clinical evaluation before regulatory approval. By simplifying oral anticoagulation, the direct oral anticoagulants have revolutionized anticoagulation care and have enhanced the uptake of anticoagulation, but bleeding has not been eliminated and there is a need for more effective and convenient anticoagulants for thrombosis triggered by the contact pathway of coagulation. The newly developed factor XIa and XIIa inhibitors have the potential to address these unmet clinical needs and are undergoing clinical evaluation for several indications. SIGNIFICANCE STATEMENT: Anticoagulant therapy is the cornerstone of treatment and prevention of thrombosis, which remains a leading cause of morbidity and mortality worldwide. Elucidation of the structure and function of coagulation enzymes, their cofactors, and inhibitors, coupled with advances in structure-based design led to the discovery of more convenient, safer, and more effective anticoagulants that have revolutionized the management of thrombotic disorders.

The 2024 European Society of Cardiology guidelines for atrial fibrillation (AF) emphasize a patient-centered approach to management, structured around the AF-CARE pathway: Comorbidity and risk factor management (C), Avoiding stroke and thromboembolism (A), Reducing symptoms through rate and rhythm control (R), and Evaluation and dynamic reassessment (E). This framework ensures that comorbidities such as hypertension, heart failure, diabetes, and obesity are effectively managed to prevent disease progression and improve outcomes. A key principle of the guidelines is shared decision making involving patients, families, caregivers, and healthcare teams to ensure individualized care that reflects patient preferences. The guidelines also stress healthcare equity, advocating for the elimination of disparities related to sex, ethnicity, disability, and socioeconomic status. For diagnosis, electrocardiographic confirmation of clinical AF is essential, followed by risk stratification using the CHA₂DS₂-VASc score to guide anticoagulation therapy. Direct oral anticoagulants are preferred for most patients because of their good safety profile. Stroke prevention is prioritized, with rhythm control as first-line treatment for suitable patients. For those with persistent symptoms despite medications, catheter ablation is recommended. Rate control strategies, including beta-blockers, digoxin, and calcium channel blockers, are used to manage heart rate and symptoms. Ongoing education for patients, families, and providers supports informed decision making and dynamic reassessment, optimizing patient outcomes and quality of life.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk of thromboembolism and stroke. Its coexistence with valvular heart disease (VHD) further complicates management due to elevated risks of thromboembolism, bleeding, and mortality. This review explores the pathophysiology of AF and its interaction with VHD, focusing on diagnostic tools like echocardiography and risk stratification scores such as CHA2DS2-VASc and HAS-BLED. Vitamin K antagonists (VKAs) remain the cornerstone of anticoagulation therapy in high-risk VHD populations, particularly in patients with mechanical heart valves or moderate-to-severe mitral stenosis (MS). VKAs have demonstrated proven efficacy in reducing thromboembolic events in these subgroups, supported by decades of clinical evidence. However, their use requires frequent international normalized ratio (INR) monitoring and is associated with higher bleeding risks, posing challenges in long-term management. Despite these limitations, VKAs are indispensable in these populations due to the lack of robust evidence supporting the safety and efficacy of direct oral anticoagulants (DOACs) in these high-risk groups. Ongoing clinical trials, such as the RIVER trial, aim to evaluate the role of DOACs in VHD. However, current guidelines continue to recommend VKAs as the standard of care for these patients. In contrast, DOACs offer significant advantages in non-valvular AF and selected VHD populations. Their predictable pharmacokinetics, fewer dietary restrictions, and lower risks of intracranial hemorrhage make them a preferred choice for many patients. Landmark trials and meta-analyses, including RE-LY, ROCKET-AF, and ARISTOTLE, have demonstrated the safety and efficacy of DOACs in non-valvular AF and certain VHD subgroups. However, DOACs are contraindicated in high-risk VHD populations, such as those with mechanical valves or moderate-to-severe MS, due to insufficient evidence and potential risks of thromboembolic events. Evolving guidelines from leading societies emphasize individualized approaches and collaborative decision-making in anticoagulation therapy. While DOACs are preferred for most AF patients, VKAs remain essential for high-risk VHD patients. Future advancements, such as factor XIa inhibitors, hold promise for improving outcomes and safety in these complex populations. This review provides a comprehensive framework for clinicians to navigate the complexities of anticoagulation in AF and VHD, ensuring evidence-based, patient-centered care.

Mitral valve transcatheter edge-to-edge repair (M-TEER) has emerged as a viable therapy option in patients with severe mitral regurgitation and high surgical risk. Although atrial fibrillation is common among patients undergoing M-TEER, the optimal anticoagulatory treatment after the intervention is unknown.

A single-center retrospective observational analysis was conducted using data from the M-TEER registry at the University Hospital Cologne collected from 2019 untill 2021 including patients undergoing M-TEER between November 2012 and April 2019. Patients with atrial fibrillation receiving consistent anticoagulation following M-TEER were categorized into a direct oral anticoagulant or a vitamin K antagonist (VKA) group. The primary end point was a composite of ischemic cerebrovascular and bleeding events. Additionally, overall survival was assessed.

Among 613 patients undergoing M-TEER, 206 met the inclusion criteria, with 61 receiving direct oral anticoagulants and 145 receiving VKAs. After a median follow-up of 833 (interquartile range, 355-1271) days, the incidence of the composite primary end point did not differ between direct oral anticoagulant and VKA groups (hazard ratio [HR], 0.51 [95% CI, 0.23-1.12]; P=0.07). Similarly, rates of ischemic cerebrovascular events and bleeding events were similar between groups. However, the overall mortality rate was higher in the VKA group (HR, 2.56 [95% CI, 1.54-4.26]; P=0.002). In the multivariable analysis, oral anticoagulation with a VKA was an independent predictor for death (adjusted HR, 2.23 [95% CI, 1.08-5.06]; P=0.03).

Our findings suggest that direct oral anticoagulants may offer comparable efficacy and safety to VKAs in preventing thromboembolic events following M-TEER in patients with atrial fibrillation. Further randomized trials are needed to confirm these results and establish optimal anticoagulation strategies in this patient population.

As the prevalence of heart failure is increasing globally, left ventricular assist devices (LVADs) have become essential therapeutic options in managing advanced heart failure. This review explores the development of LVAD technology, with a focus on the shift from pulsatile to continuous-flow devices, particularly the HeartMate 3, the most advanced generation of LVADs. The evolution in design has significantly enhanced patient survival and quality of life. However, hemocompatibility-related adverse events (HRAEs)-such as pump thrombosis, ischemic and hemorrhagic strokes, and gastrointestinal bleeding-remain major clinical challenges. Striking the delicate balance between preventing thromboembolic events and minimizing hemorrhagic risks remains critical in LVAD patient management. Current therapeutic strategies typically involve long-term anticoagulation with vitamin K antagonists and antiplatelet therapy, though optimal management must be individualized based on patient-specific factors and device characteristics. Emerging alternatives, including low-dose anticoagulation, direct oral anticoagulants such as apixaban, and aspirin-free regimens, offer promising potential to reduce adverse outcomes. This review also highlights the role of innovative mechanical designs in minimizing shear stress and alternative treatments in preventing complications like gastrointestinal bleeding. Despite these advancements, personalized treatment strategies are critical, as no single therapeutic regimen fits all LVAD recipients. Ongoing research into both device technology and pharmacological therapies is essential to further reduce HRAEs and improve long-term outcomes for LVAD patients.

With the aging of the general population and the rise in surgical and transcatheter aortic valve replacement, there will be an increase in the prevalence of prosthetic aortic valves. Patients with prosthetic aortic valves can develop a wide range of unique pathologies compared to the general population. Accurate diagnosis is necessary in this population to generate a comprehensive treatment plan. Transthoracic echocardiography is often insufficient alone to diagnose many prosthetic valve pathologies. The integration of many imaging modalities, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, and nuclear imaging, is necessary to care for patients with prosthetic valves. The purpose of this review is to describe the strengths, limitations, and contemporary use of the different imaging modalities necessary to diagnose prosthetic valve dysfunction.

Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually.

Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher.

Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.

Direct oral anticoagulants (DOACs) do not require routine monitoring of anticoagulant effect, but measuring DOAC activity may be desirable in specific circumstances to detect whether clinically significant DOAC levels are present (eg, prior to urgent surgery) or to assess whether drug levels are excessively high or excessively low in at-risk patients (eg, after malabsorptive gastrointestinal surgery). Routine coagulation tests, including the international normalized ratio (INR) or activated partial thromboplastin time (aPTT), cannot accurately quantify drug levels but may provide a qualitative assessment of DOAC activity when considering the estimated time to drug clearance based on timing of last drug ingestion and renal and hepatic function. Drug-specific chromogenic and clot-based assays can quantify drug levels but they are not universally available and do not have established therapeutic ranges. In this review, we discuss our approach to measuring DOAC drug levels, including patient selection, interpretation of coagulation testing, and how measurement may inform clinical decision-making in specific scenarios.

The management of anticoagulation in patients with durable left ventricular assist devices (LVADs) is challenging. Traditionally, warfarin has been used, but its limitations have prompted interest in direct oral anticoagulants (DOACs). This meta-analysis aims to evaluate the safety and efficacy of DOACs compared to warfarin in LVAD patients.

We searched databases for studies comparing DOACs and warfarin in LVAD patients. Primary outcomes were thromboembolic events and major bleeding events. Secondary outcomes were the individual components of the thromboembolic events, minor bleeding events, and all-cause mortality. Random-effects model was used to calculate log risk-ratios (RR) with 95 % confidence intervals (CI).

Nine studies with a total of 316 LVAD patients (153 on DOACs, 163 on warfarin) were included. Thromboembolic events were similar between the groups (Log RR -0.42, 95 % CI:1.29 to 0.45, P = 0.34). Major bleeding events were significantly fewer in the DOAC group (Log RR -1.05, 95 % CI:1.73 to -0.36, P < 0.01). Minor bleeding events were also less common with DOACs (Log RR -0.77, 95 % CI:1.46 to -0.07, P = 0.03). No significant differences were observed in pump thrombosis, ischemic cerebrovascular accident events, or all-cause mortality.

DOACs appear to be a safe and effective alternative to warfarin for anticoagulation in LVAD patients, associated with fewer major and minor bleeding events. These findings support the consideration of DOACs in this patient population, though further research is needed to confirm these results and guide clinical practice.

To evaluate whether warfarin targeted at an international normalized ratio of 1.8 (range, 1.5-2.0) after On-X mechanical aortic valve implant is safe for all patients.

This prospective, observational clinical registry assessed adverse event rates in adult patients receiving low-dose warfarin (target international normalized ratio, 1.8; range, 1.5-2.0) plus daily aspirin (75-100 mg) during a 5-year period after On-X aortic valve implant. The primary end point is the combined rate of major bleeding, valve thrombosis, and thromboembolism overall and in 4 subgroups. The comparator is the Prospective Randomized On-X Anticoagulation Trial control group patients on standard-dose warfarin (international normalized ratio, 2.0-3.0) plus aspirin 81 milligrams daily.

A total of 510 patients were recruited at 23 centers in the United States, United Kingdom, and Canada between November 2015 and January 2022. This interim analysis includes 229 patients scheduled to complete 5-year follow-up by August 16, 2023. The linearized occurrence rate (in percent per patient-year) of the primary composite end point of major bleeding, valve thrombosis, and thromboembolism is 1.83% compared with 5.39% (95% confidence interval, 4.12%-6.93%) in the comparator group. Results are consistent in clinic-monitored and home-monitored patients and in those at high risk for thromboembolism. Major bleeding and total bleeding were reduced by 87% and 71%, respectively, versus the comparator group, without an increase in thromboembolic events.

Interim results support the continued safety of the On-X aortic mechanical valve with a target international normalized ratio of 1.8 plus low-dose aspirin through 5 years after implant, with or without home monitoring.

Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure.

Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients.

This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management.

The available data on anticoagulation therapy in real-world primary care settings for atrial fibrillation (AF) patients at high risk of stroke is limited.

To evaluate anticoagulation therapy and elucidate the factors associated with the selection between direct oral anticoagulants (DOACs) and warfarin.

This is a retrospective cohort study that included patients ≥ 18 years old at a large primary care outpatient group, a network of twenty clinics in the northeast United States between January 4, 2021 - January 4, 2023.

Oral anticoagulation therapy in AF patients with high risk of stroke (CHA2DS2-VASc score of ≥ 2 in men or ≥ 3 in women).

Among the 3,118 adult patients with AF and high risk of stroke (median age 77.90, IQR 71.66-84.50 years; male 57.6%), we found that older age (aOR 1.40, p = 0.003), greater BMI (25-29.9: aOR 1.32, p = 0.048; ≥ 30 aOR 1.42, p = 0.010), and taking more than five medications (aOR 2.28, p < 0.001) were more likely to be on an oral anticoagulant. Among those taking an OAC, having Medicare as the sole coverage (aOR 0.53, p = 0.032), male gender (aOR 0.69, p = 0.011), worse renal function (aOR 0.80, p = 0.021), and higher CHA2DS2-VASc score (aOR 0.88, p = 0.024) are more likely to be on warfarin than a DOAC. Patients taking more than five medications daily (6-10 medications: aOR 1.92, p = 0.013; ≥ 16: aOR = 2.10, p = 0.006) were more likely to be on an anticoagulant and may receive a DOAC over warfarin.

AF with high stroke risk adult patients are more likely to be on an oral anticoagulant if they are older, having BMI ≥ 25, or taking more than five medications. Medicare as the sole coverage, male gender, worse renal function, and higher CHA2DS2-VASc scores are factors associated with greater warfarin usage, while patients taking over five daily medications are more likely to be prescribed DOACs.

Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics. Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed. Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022; P = .45). Patient demographics did not significantly vary, which may be due to the clinic retaining 45% of patients between both time periods. Contraindications to DOAC therapy were identified in 39% of the 2015 group and 49% of the 2022 group (P = .18). The most common contraindication was indication for anticoagulation. Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients.

Over the last decade, the advent of direct oral anticoagulants (DOACs) has rapidly changed the landscape of anticoagulation. In the early 2010s, DOACs became widely available for stroke prevention in atrial fibrillation and the treatment of venous thromboembolism. About 10 years later, approximately two-thirds of patients requiring oral anticoagulant treatment were receiving a DOAC. The results of several post-marketing studies consistently confirmed the findings of phase 3 clinical trials, and research has focused on new areas of development, with heterogeneous results. A role for DOACs has emerged for patients with peripheral artery disease and other challenging conditions, such as cancer-associated thrombosis, unusual-site venous thromboembolism, and end-stage renal disease. Conversely, clinical trials showed that DOACs were not efficacious in patients with valvular atrial fibrillation, mechanical heart valves, embolic strokes of undetermined source, or antiphospholipid syndrome. In this Review, we discuss the impact of DOACs in clinical practice over the last decade, new areas under development, and practical issues in the management of these drugs.

Direct oral anticoagulants (DOACs) have transformed the landscape of antithrombotic therapy in the past two decades. However, there is uncertainty about when they should or should not be used for treatment or prevention of thromboembolic events. DOACs have largely replaced warfarin for many patients with atrial fibrillation or venous thromboembolism who require anticoagulant therapy. In addition to noninferior efficacy, fewer drug-drug and food-drug interactions and improved convenience; DOACs have been shown to reduce the risk of intracranial hemorrhage. They have also received new indications compared with warfarin, such as cardiovascular risk reduction in patients with stable atherosclerotic diseases. However, there are some scenarios in which DOACs are associated with inferior efficacy or worse safety compared with standard treatment, such as warfarin. These include patients with mechanical heart valves, thrombotic antiphospholipid syndrome, and others. Although DOACs offer a streamlined and convenient option for the management of many patients with or at risk of thromboembolic events, their use should be avoided in certain high-risk scenarios. This minireview summarizes such conditions and those in which there is uncertainty for use of DOACs for particular diseases or particular patient subgroups.

Thromboembolic disorders globally contribute to morbidity and mortality, emphasizing adequate anticoagulation and thrombosis management. Therapeutic advances are essential in preventing complications like pulmonary embolism, stroke, and myocardial infarction. This review summarizes recent anticoagulation advances, current challenges, future directions, and novel anticoagulants and drug delivery systems on clinical outcomes.

This paper assesses the effectiveness and safety of new anticoagulants through a systematic review of recent clinical trials, meta-analyses, and guideline publications. Key studies, including PACIFIC-AF, RIVER, ENAVLE, ENVISAGE-TAVI AF, and ARCADIA, were analyzed to provide a perspective on therapeutic advancements.

The review highlights key findings from vital clinical trials. Asundexian, in the PACIFIC-AF trial, demonstrated a 34% reduction in bleeding events compared to Apixaban. In the RIVER trial, Rivaroxaban reduced significant bleeding events by 20% compared to warfarin in patients with bioprosthetic mitral valves. In the ENAVLE trial, Edoxaban achieved a 3.7% decrease in thromboembolic events compared to warfarin without increasing significant bleeding rates. In the ENVISAGE-TAVI AF trial, edoxaban was noninferior to VKAs in preventing thromboembolic events but showed a slight increase in major bleeding events by 1.5%. Lastly, the ARCADIA trial highlighted that apixaban did not significantly reduce recurrent stroke risk compared to aspirin, with both treatments having an annualized stroke rate of 4.4%.

Advances in anticoagulant therapies and drug delivery systems aim to enhance patients' clinical outcomes for thromboembolic disorders. While recent trials show promising data, ongoing patient-specific responses and monitoring challenges require further research. Continuous innovation and investigation are essential to refine anticoagulation practices and tailor treatments.

Direct oral anticoagulants (DOACs) have been used clinically in patients with chronic thromboembolic pulmonary hypertension (CTEPH) for secondary prevention after acute venous thromboembolism, although the data are limited. We evaluated the effects of DOACs-especially factor Xa (FXa) inhibitors-by measuring anti-factor Xa activity (AXA). Fifty consecutive CTEPH patients treated with rivaroxaban, apixaban, or edoxaban were enrolled. Heparin-calibrated AXA was measured at peak and trough. The median peak heparin-calibrated AXA across all 50 patients was 1.90 IU/mL and was comparable among the three FXa inhibitors. At trough, heparin-calibrated AXA was significantly higher in apixaban-treated patients (median 0.70 IU/mL) than in those given rivaroxaban (median 0.11 IU/mL) or edoxaban (median 0.11 IU/mL, p < 0.001). Peak heparin-calibrated AXA was significantly lower with reduced-dosage FXa inhibitor (edoxaban 30 mg/day) than with the reference dosage (edoxaban 60 mg/day, apixaban 10 mg/day, or rivaroxaban 15 mg/day, p = 0.01). The heparin-calibrated AXA of both rivaroxaban and apixaban was strongly significantly correlated with the plasma concentration of each drug. The cumulative rate of major and clinically relevant non-major bleeding was significantly higher in patients with peak heparin-calibrated AXA ≥ 2.09 IU/mL. Heparin-calibrated AXA could provide useful information for treating CTEPH patients with FXa inhibitors.

Antithrombotic therapy is the mainstay of ischemic stroke prevention. Current drugs (antiplatelets and oral anticoagulants) lead to increased bleeding risks, and the rates of stroke recurrence, despite antithrombotic therapy, are still elevated. There is a need for novel antithrombotic therapies with superior effectiveness but without increased bleeding risk. Factor XIa inhibitors might cover this gap.

This manuscript examines the pharmacokinetic and pharmacodynamic properties of asundexian and the current clinical evidence regarding its application in preventing ischemic stroke.

Asundexian shows a very favoring pharmacokinetic profile. Despite asundexian being inferior to apixaban for cardioembolic ischemic stroke, it could be useful in patients with non-cardioembolic ischemic stroke. Although antiplatelet therapy is the recommended treatment to prevent non-cardioembolic ischemic stroke, adding an anticoagulant might have beneficial effects through the dual-pathway inhibition strategy. Due to the potential risk of hemorrhagic transformation, there is hesitation to administer anticoagulants early to patients who have recently had an ischemic stroke, especially if they are also on antiplatelet therapy. However, clinical trials on asundexian confirmed its safety for bleeding, even when used with antiplatelets. A phase 3 trial is currently investigating the efficacy of asundexian in preventing non-cardioembolic ischemic stroke.

Left atrial appendage (LAA) occlusion (LAAO) is performed to prevent LAA thrombus in patients with atrial fibrillation (AF). The risk of device-related thrombus (DRT) on the atrial side of the LAAO device is approximately 4%. Identifying patients at high risk of DRT would enable closer surveillance and more-aggressive anticoagulation to prevent post-LAAO DRT-related stroke.

From the LAAO registry at The University of Kansas Medical Center, we identified patients who developed DRT. We chose 3 unmatched controls per DRT case from LAAO recipients without DRT. Predictor variables were obtained from transesophageal echocardiogram reports and/or images, transthoracic echocardiogram reports, and chart review. Implant depth was measured from the limbus of the left atrial ridge to the centre of the atrial aspect of the LAAO device, on a 45° transesophageal echocardiogram view.

We identified 26 patients with DRT (aged 77.7 ± 9.7 years; 34.6% female) and selected 78 unmatched controls without DRT. Univariate predictors of DRT, comprising a novel TED-F2 score, included history of venous Thromboembolism (23.1% vs 5.1%, P = 0.01), an LAA Emptying velocity ≤ 20 cm/s (45.8% vs 18.9%, P = 0.01), an implant Depth > 2 cm (34.6% vs 12.8%, P = 0.02), and presence of AF rhythm at time of device implantation (50.0 % vs 11.5%, P = 0.0001). A TED-F2 score of ≥ 3 was very strongly associated with DRT-odds ratio 12.5 (95% confidence interval, 3.8-41.1, P < 0.0001).

We propose a novel risk score to predict development of DRT after LAAO, comprising history of venous Thromboembolism, LAA Emptying velocity ≤ 20 cm/s, implant Depth > 2 cm (1 point each), and an AF rhythm at implantation (2 points). A TED-F2 risk score of ≥ 3 identified patients who are at greatly elevated risk of developing DRT.

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.