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Direct Oral Anticoagulants (DOACs) have revolutionized the treatment of thromboembolic disorders, offering targeted, effective, and safer alternatives to traditional anticoagulants like heparins and vitamin K antagonists (VKAs). Despite their benefits, DOACs have drawbacks, including an increased risk of gastrointestinal bleeding and unsuitability for patients with mechanical heart valves. Recent research has highlighted Factor XI (FXI) as a promising anticoagulation target due to its significant role in pathological thrombosis and minor involvement in normal hemostasis. Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a comprehensive analysis of abelacimab, examining its clinical pharmacology and its pharmacokinetic and pharmacodynamic properties. It scrutinizes abelacimab's safety profile and key monitoring parameters. The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis.

Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real‐world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random‐effect meta‐analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113–154, I2 = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69–91, I2 = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography–tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy. [ABSTRACT FROM AUTHOR]

Cutaneous leukocytoclastic vasculitis (LCV) is type of small vessel vasculitis that commonly presents as palpable purpura involving the lower extremities and buttocks. Approximately half of cases are idiopathic, but the disease may be triggered by infection, drug reaction, inflammatory disease, or other causes. We report a case of leukocytoclastic vasculitis secondary to the novel anticoagulant rivaroxaban (Xarelto®).

Direct Oral Anticoagulants (DOACs) have revolutionized the treatment of thromboembolic disorders, offering targeted, effective, and safer alternatives to traditional anticoagulants like heparins and vitamin K antagonists (VKAs). Despite their benefits, DOACs have drawbacks, including an increased risk of gastrointestinal bleeding and unsuitability for patients with mechanical heart valves. Recent research has highlighted Factor XI (FXI) as a promising anticoagulation target due to its significant role in pathological thrombosis and minor involvement in normal hemostasis. Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a comprehensive analysis of abelacimab, examining its clinical pharmacology and its pharmacokinetic and pharmacodynamic properties. It scrutinizes abelacimab's safety profile and key monitoring parameters. The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aims: Design and synthesis of a novel 3, 3′, 4′, 5, 7-O- pentasulfated Quercetin (QPS) as an activator of protein disulfide isomerase (PDI). Main Methods: Based on an in silico analysis we show that QPS binds to a and b domain of PDI (−7.4 kcal/mol) unlike PDI inhibitor quercetin 3-rutinoside (Q3R) that binds at substrate-binding domain b (−8.0 kcal/mol). QPS was synthesized and its structure validated using a combination of FTIR, NMR and mass spectral studies. Surprisingly, unlike Q3R QPS is shown to enhance the activity of purified recombinant PDI. Fluorometric and circular dichroism analysis showed that QPS binds to a unique site on PDI with marginal variations in its secondary structure. Key Findings: Hypersulfation of quercetin reverses its inhibitory effect on PDI as addition of exogenous PDI and QPS in human plasma showed increase in rate of coagulation, unlike Q3R which shows a decrease. Significance: The results indicate QPS to be a novel enhancer of PDI activity that can influence the coagulation rates in plasma. QPS has therapeutic potential to control bleeding.

The increasing prevalence of stroke, with an estimated annual cost of $71.5 billion, has made it a major health problem that increases disability and death, particularly in patients with atrial fibrillation. Although advanced age and atrial fibrillation are recognized as strong risk factors for stroke, the basis for this susceptibility are not well defined. Aging or associated diseases are accompanied by changes in rheostatic, humoral, metabolic and hemodynamic factors that may contribute more to stroke predisposition than rhythm abnormality alone. Several thromboembolism-predisposing clinical characteristics and serum biomarkers with prognostic significance have been identified in patients with atrial fibrillation. Although anticoagulation decreases the risk of thromboembolism, management in the elderly remains complex due to major concerns about bleeding. New anticoagulants and nonpharmacologic strategies are helpful to reduce the risk of bleeding, particularly in older-elderly patients. Herein, we review the pathogenesis and management of select issues of thromboembolism in the elderly with atrial fibrillation.

Background: The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke. Methods: A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013. Results: Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). Conclusion: There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF. [ABSTRACT FROM AUTHOR]

The practice of outpatient general internal medicine requires a diverse and evolving knowledge base. General internists must identify practice-changing shifts in the literature and reflect on their impact. Accordingly, we conducted a review of practice-changing articles published in outpatient general internal medicine in 2014. To identify high-quality, clinically relevant publications, we reviewed all titles and abstracts published in the following primary data sources in 2014: New England Journal of Medicine, Journal of the American Medical Association (JAMA), Annals of Internal Medicine, JAMA Internal Medicine, and the Cochrane Database of Systematic Reviews. All 2014 primary data summaries from Journal Watch-General Internal Medicine and ACP JournalWise also were reviewed. The authors used a modified Delphi method to reach consensus on inclusion of 8 articles using the following criteria: clinical relevance to outpatient internal medicine, potential for practice change, and strength of evidence. Clusters of important articles around one clinical question were considered as a single-candidate series. The article merits were debated until consensus was reached on the final 8, spanning a variety of topics commonly encountered in outpatient general internal medicine. [ABSTRACT FROM AUTHOR]

Rivaroxaban is a novel anticoagulant approved for use in patients with atrial fibrillation for stroke prevention. It is a factor Xa inhibitor, and its activity cannot be monitored with use of the international normalized ratio. A 5.6% chance of major bleeding is associated with rivaroxaban use, including intracranial and gastrointestinal bleeds. We report the first case, to our knowledge, of isolated hemopericardium related to rivaroxaban use, which could potentially lead to death from cardiac tamponade. A 76-year-old man who was receiving rivaroxaban for atrial fibrillation presented to the emergency department with pleuritic chest pain and was found to have a hemopericardium. No signs of tamponade were evident, and his bleed remained stable after discontinuing rivaroxaban. The patient had also been taking saw palmetto, which may have contributed to the bleed by increasing rivaroxaban activity. A work-up for other causes of hemopericardium, including pacemaker lead misplacement and autoimmune disease-related pericarditis, was negative. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hemopericardium and rivaroxaban use. This case highlights the potential for bleeding complications associated with novel anticoagulants. Herbal products and various drugs may increase rivaroxaban levels by inhibiting P-glycoprotein and cytochrome P450 3 A4 activity. Clinicians should be aware of these potential interactions with rivaroxaban and perform a review of not only the patient's drug therapy but also any herbal and food products that could alter the levels of anticoagulants. The lack of an antidote and the inability to dialyze rivaroxaban is a significant concern in situations of life-threatening bleeds. A laboratory test for monitoring rivaroxaban levels may be required for its safe use. [ABSTRACT FROM AUTHOR]

The use of novel anticoagulants such as dabigatran are increasing. Despite increased risks of intracerebral haemorrhage with warfarin among Asians, there is little published data on dabigatran to assess 'real world' efficacy and safety of dabigatran therapy in Asia. This was a retrospective observational study of patients prescribed dabigatran between 2010 and 2013. Data was available for 510 patients: median age 68 years (range 20-91), median CHA2DS2-VASc score was 2 and median HAS-BLED score was 2. The average follow-up duration of 315 days (range: 1-1,096). The overall discontinuation rate was 16 % after a median 252 days of treatment with dabigatran. There were 17 (3.3 %) patients with minor bleeding, 2 (0.4 %) had major bleeding episodes. 20 patients (3.9 %) developed dyspepsia which was the most common side effect. The rate of occurrences of adverse effects and bleeding were lower than those seen in the RE-LY trial. None of the patients had an ischaemic stroke, 1 (0.2 %) patient had a haemorrhagic stroke. Out of 510 patients, 158 patients (31 %) were switched to dabigatran from warfarin. This showed that patients frequently preferred the dabigatran due to convenience when given a choice to switch from warfarin. We report one of the largest registry of Asian patients. Reassuringly, we found that our cohort had a low rate of rate of ischaemic stroke, low rates of side effects and bleeding with the drug. [ABSTRACT FROM AUTHOR]

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. [ABSTRACT FROM AUTHOR]

Many pharmacologic options are available for prevention and treatment of venous thromboembolism (VTE). The anticoagulant selected may vary according the individual patient situation such as the acute versus chronic setting, renal function and indication for either VTE prevention or treatment. Established methods of pharmacologic prophylaxis agents include heparinoids, injectable anti-Xa inhibition and vitamin K antagonists (VKA). The novel anticoagulants have recently been incorporated into orthopedic surgery prophylaxis pathways and can be used for VTE treatment. Chronic VTE management, however, has largely been managed with the use VKA. The advantages of VKA include low cost, familiarity with use, and established protocols to manage catastrophic bleeding. VKA use, however, poses hurdles including the fact that correct dosing can be empiric, the existence of multiple potential medication and dietary interactions, and the possiblity for complications when anticoagulation levels are not well monitored. In contrast, the novel anticoagulants offer ease of dosing, reliable pharmacokinetics and low risk of interactions with other medications or diet. Potential hazards of the novel anticoagulants include high costs, questionable therapeutic benefit in those with poor adherence, a reliance on renal clearance, lack of reliable reversibility in the event of catastrophic bleeding, as well as incomplete familiarity with use by the general practitioner. Although clinical trials demonstrate promise of greater applicability of use of these novel agents, hospital systems will need to simultaneously create a plan for appropriate management of the use of these agents, an anticoagulation stewardship program. As guidelines are adopted to prevent and manage VTE, an appreciation for this new level of complexity is essential. [ABSTRACT FROM AUTHOR]

The article offers information on a study which determined whether warfarin and other vitamin K antagonists (VKA) can be considered as replacement therapy for the prevention and treatment of venous and arterial thromboembolism in patients with atrial fibrillation. The anticoagulants studied were edoxaban, rivaroxaban, apixaban and dabigatran. Findings showed that warfarin's use is restricted by its narrow therapeutic index that requires frequent monitoring and dose adjustments.

Background & Aims Non–vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs. Methods We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug. Results Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80–1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64–1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77–1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67–1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04–1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15–1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64–1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78–1.11). These subgroup findings were not observed in other sensitivity analyses. Conclusions In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the stroke risks caused by atrial fibrillation in old patients which warfarin anticoagulation manages to meet the needs of patients for adequate stroke protection. The author mentions that large unmet needs exist in patients who do not take warfarin. He elaborates that compared with aspirin, warfarin is more effective in regular coagulation monitoring and stroke prevention.

A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?' Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The novel oral anticoagulant agents (NOACs) assessed in the included studies were dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Factor Xa inhibitor). Dabigatran was included in all five studies and showed bleeding complication rates of 0-4%. Rivaroxaban was included in one study and had bleeding complication rates of 4%. Warfarin was a comparator agent in three studies and had bleeding complication rates of 4.6-8%. The incidence rate of thromboembolic complications was 0-1% with dabigatran and 0% with rivaroxaban and warfarin in all studies. Based on the available studies, there is no evidence of significantly increased risk of bleeding or thromboembolic events with NOACs compared with warfarin when used at the time of cardiac rhythm device implantation. However, not all patients in the studies were actually receiving the specified NOAC at the time of device implantation, thereby limiting the available evidence., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers.Methods: We used medical and prescription claims data from a large insurer to identify patients with nonvalvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin versus a novel anticoagulant.Results: There were 6893 patients with atrial fibrillation that initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (P <.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant.Conclusions: This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research. [ABSTRACT FROM AUTHOR]

Background The safety of recombinant tissue plasminogen activator (rt-PA) and/or endovascular therapy for patients using the novel oral anticoagulant (NOAC) for atrial fibrillation remains unclear. Methods We report a patient who was treated by both rt-PA and endovascular thrombectomy who suffered from acute ischemic stroke under treatment with NOAC. Results An 83-year-old woman had a medical history with ischemic stroke due to paroxysmal atrial fibrillation and was then administered 10 mg of rivaroxaban daily. Although she took rivaroxaban in the morning, ischemic stroke recurred at midnight of that day. Soon after transferring to our hospital, we confirmed right middle cerebral artery (MCA) occlusion in the patient and then initiated treatment with intravenous rt-PA. Although no hemorrhagic complication occurred, recovery of her symptoms was not seen, and endovascular thrombectomy was performed. Although the inferior branch of the MCA was recanalized, an infarct was seen in her left frontal lobe. Hemorrhagic transformation was not observed during or after these combined treatments. Conclusions Thrombolysis and/or endovascular thrombectomy might be safe for patients treated with the new anticoagulant rivaroxaban. [ABSTRACT FROM AUTHOR]