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Introduction: Anticoagulants have been discovered and developed over past 100 years. At the beginning unfractionated heparin found its applications, just later to fade into the background of newer and more effective drugs. Patients have been treated with more and more progressive medications -- Low-Molecule-Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and Novel Oral Anticoagulants (NOAC). All of them have many indications but most importantly they are used in prophylaxis and treatment of venous thromboembolism (VTE). Scientists and physicians have been working for years to come up with the perfect drug that has fewer contraindications, side effects and doesn't need continuous anticoagulant monitoring. As for today, deemed a turning point in anticoagulant therapy are inhibitors of factor XI. It is a ground-breaking innovation as it ensures high prevention of thrombotic episodes and guarantees intact physiological hemostasis. Current State of Knowledge: The coagulation cascade and molecules part taking in that have been discovered and described extensively and in detail. Historically, the demand for anticoagulants was always a burning subject. A huge progress has been made in the last one hundred years. Treatment which clinicians are using currently is a combination of drugs used in the past and the novel forms. Unfractionated heparin is the oldest out of all and despite its simple action mechanism and adverse effects, is still a requested drug. Its lighter form, low-molecule-weight-heparin (LMWH) is an enhancement to the previous treatment due to its higher bioavailability and fewer side effects. Vitamin K antagonists (VKAs) are widely spread in medical environment thanks to their expanded mechanism of action, oral administration and reversibility of their overdose, as well as their well-developed anti-side effect therapy. Novel Oral Anticoagulants (NOACs) have been introduced to the market about 10 years ago. In spite of NOACs short period of clinical use, they were a huge change to the previous treating methods. No need of constant checking the coagulation times was a great convenience to both patients and doctors. Currently, the newest innovation in anticoagulant therapy are inhibitors of factor XI. Even though it still undergoes clinical trials, the outcome is promising for the future. Summary: The present article discusses history of anticoagulant drugs, their mechanism of action and usage but also focuses on the recent perspectives and developments as new anticoagulant drugs are being put to the test in therapeutic trials. The review underlines the importance and a big demand for improvements in old therapeutic methods and exploring the new, more suitable ones. [ABSTRACT FROM AUTHOR]

Background and Objectives Familiarity with dental management to control bleeding in patients taking anticoagulant drugs is necessary. Purpose of this study was to investigate level of awareness of general dentists and final year dental students of Yazd about dental management for patients prone to unusual bleeding in 2023. Materials and Methods This cross-sectional study selected 135 general dentists and final-year general dental students in Yazd using convenient sampling. Level of knowledge was evaluated using the questionnaire of Moshaverinia et al., which was valid and reliable. Data were analyzed using Mann-Whitney and Kruskal-Wallis statistical tests of SPSS V.25 statistical software. Results 50 of the general dentists were male (58.8%), 35 were female (41.2%), 28 of the students were male (56%), 22 were female (44%). Mean ages of general dentists and students were 29.20 ± 4.93 and 25.16 ± 1.63, respectively. Average knowledge score of dental students was 8.72 ± 2.67 (Range: 1-14), while that of general dentists was 8.20 ± 2.86 (Range:2-15). There was no statistically significant difference between average knowledge score of general dentists and variables such as age, gender, work experience and university. There was no statistically significant difference between average score of students' knowledge and variables of age, gender and academic semester. There was no statistically significant difference between the average knowledge score of general dentists and students. Conclusions The results showed general dentists and final-year dental students in Yazd had moderate knowledge of dental management for coagulopathic patients. [ABSTRACT FROM AUTHOR]

AbstractThe combination of an anticoagulant and a hypolipidemic agent is commonly used in patients at risk for stroke because it controls thrombosis and lowers cholesterol levels. However, the use of anticoagulants carries a high risk of life-threatening bleeding. To address the need for personalized clinical monitoring and risk management, we developed a rapid and sensitive HPLC method with a streamlined sample preparation process. This method enables the simultaneous determination of concentrations for two commonly used anticoagulant drugs (apixaban and rivaroxaban) and three hypolipidemic drugs (rosuvastatin, atorvastatin calcium, and simvastatin). The chromatographic conditions and sample preparation methods were optimized. The drugs were well separated by the gradient elution of phosphoric acid (0.01%, v/v) and acetonitrile at a flow rate of 1.0 mL/min within 40 min on an Athena C18-WP column (4.6 × 150 mm, 5-μm particle size). The proposed method was linear (r2 ≥ 0.994) within the concentration ranges of 0.22–20 μg·mL−1 for the five analytes, including the expected range of therapeutic concentrations. This method enables simultaneous monitoring of the levels of the mentioned drugs in clinical practice. Furthermore, the chromatographic conditions were simple and feasible, making them highly suitable for emergency clinical medication monitoring in basic medical institutions. [ABSTRACT FROM AUTHOR]

Objective Many guidelines indicate that continuous use of anticoagulant drugs reduces the incidence of venous thrombus (VT), but no studies show the effect on the incidence of symptomatic venous thrombus (SVT) in total knee arthroplasty (TKA) patients after discharge. This study aimed to investigate whether it is necessary to apply anticoagulants to TKA patients after discharge. Methods Patients who met the exclusion criteria requirement, underwent TKA by the same surgical team and received anticoagulant therapy after the operation were eligible for the study. Finally, a total of 567 TKA patients were recruited as participants. The patients were divided into two groups. The patients in group A were taken low molecular heparin for 5–10 days after surgery, which included but was not limited to low molecular weight heparin calcium injection (0.4 mL, ih, Qd), calcium dioxin injection (0.6 mL, ih, Qd), or enoxaparin sodium injection (0.4 mL, ih, Qd), and the patients needed to continue oral anticoagulant drug (10 mg, po, Qd) for 7–21 days after discharge. The patients in group B only took low molecular heparin 5–10 days after surgery and no treatment after discharge. The baseline characteristics of patients, total complications of SVT include lower limb vascular pain (LLVP), lower limb vascular pain no fester (LLVPNF), lower limbs swelling (LLS), lower limb fester (LLF), and death by thrombosis (DT), bleeding and mortality following discharged were compared between two groups. Results The study showed that the incidence of SVT patients had no significant difference between the two groups (p = 0.489). Moreover, the incidence of LLVP (p = 0.265), LLS (p = 0.84), LLVPNF (p = 0.213), LLF (p = 0.907), DT (p = 0.907), death from other causes, and bleeding (p = 0.323) had no significant differences between the two groups. However, the incidence of SVT in patients with smoking (p = 0.0001 or 0.0011) or drinking (p = 0.0002 or 0.0001) was significantly increased. Conclusion There is not enough evidence showing that the TKA patients given anticoagulants after discharge had benefits in decreasing the risk of SVT. Furthermore, smoking and drinking would significantly increase the risk of SVT in TKA patients.

Background Direct oral anticoagulants (DOACs) are recommended as first-line treatment of atrial fibrillation. Whether DOAC use is associated with lower risks of kidney complications compared with vitamin K antagonists (VKAs) remains unclear. We examined this association in a nationwide, population-based cohort study. Methods We conducted a cohort study including patients initiating oral anticoagulant treatment within 3 months after an atrial fibrillation diagnosis in Denmark during 2012–18. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intention-to-treat approach for acute kidney injury (AKI) and chronic kidney disease (CKD) progression. We used propensity-score weighting to balance baseline confounders, computed weighted risks and weighted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing DOACs with VKAs. We performed several subgroup analyses and a per-protocol analysis. Results We included 32 781 persons with atrial fibrillation initiating oral anticoagulation (77% initiating DOACs). The median age was 75 years, 25% had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2, and median follow-up was 2.3 (interquartile range 1.1–3.9) years. The weighted 1-year risks of AKI were 13.6% in DOAC users and 15.0% in VKA users (HR 0.86, 95% CI 0.82; 0.91). The weighted 5-year risks of CKD progression were 13.9% in DOAC users and 15.4% in VKA users (HR 0.85, 95% CI 0.79; 0.92). Results were similar across subgroups and in the per-protocol analysis. Conclusions Initiation of DOACs was associated with a decreased risk of AKI and CKD progression compared with VKAs. Despite the potential limitations of observational studies, our findings support the need for increased clinical awareness to prevent kidney complications among patients who initiate oral anticoagulants. [ABSTRACT FROM AUTHOR]

Copyright of Medicus (1330-013X) is the property of Pliva Hrvatska d.o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Many guidelines indicate that continuous use of anticoagulant drugs reduces the incidence of venous thrombus (VT), but no studies show the effect on the incidence of symptomatic venous thrombus (SVT) in total knee arthroplasty (TKA) patients after discharge. This study aimed to investigate whether it is necessary to apply anticoagulants to TKA patients after discharge. Methods: Patients who met the exclusion criteria requirement, underwent TKA by the same surgical team and received anticoagulant therapy after the operation were eligible for the study. Finally, a total of 567 TKA patients were recruited as participants. The patients were divided into two groups. The patients in group A were taken low molecular heparin for 5–10 days after surgery, which included but was not limited to low molecular weight heparin calcium injection (0.4 mL, ih, Qd), calcium dioxin injection (0.6 mL, ih, Qd), or enoxaparin sodium injection (0.4 mL, ih, Qd), and the patients needed to continue oral anticoagulant drug (10 mg, po, Qd) for 7–21 days after discharge. The patients in group B only took low molecular heparin 5–10 days after surgery and no treatment after discharge. The baseline characteristics of patients, total complications of SVT include lower limb vascular pain (LLVP), lower limb vascular pain no fester (LLVPNF), lower limbs swelling (LLS), lower limb fester (LLF), and death by thrombosis (DT), bleeding and mortality following discharged were compared between two groups. Results: The study showed that the incidence of SVT patients had no significant difference between the two groups (p = 0.489). Moreover, the incidence of LLVP (p = 0.265), LLS (p = 0.84), LLVPNF (p = 0.213), LLF (p = 0.907), DT (p = 0.907), death from other causes, and bleeding (p = 0.323) had no significant differences between the two groups. However, the incidence of SVT in patients with smoking (p = 0.0001 or 0.0011) or drinking (p = 0.0002 or 0.0001) was significantly increased. Conclusion: There is not enough evidence showing that the TKA patients given anticoagulants after discharge had benefits in decreasing the risk of SVT. Furthermore, smoking and drinking would significantly increase the risk of SVT in TKA patients. [ABSTRACT FROM AUTHOR]

Introduction: Anticoagulants have been discovered and developed over past 100 years. At the beginning unfractionated heparin found its applications, just later to fade into the background of newer and more effective drugs. Patients have been treated with more progressive medications – Low-Molecule-Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and Novel Oral Anticoagulants (NOAC). As for today, deemed a turning point in anticoagulant therapy are inhibitors of factor XI. It is a ground-breaking innovation as it ensures high prevention of thrombotic episodes and guarantees intact physiological hemostasis.Current State of Knowledge: The coagulation cascade and molecules part taking in that have been discovered and described extensively and in detail. Unfractionated heparin is the oldest out of all and despite its simple action mechanism and adverse effects, is still a requested drug. Its lighter form, low-molecule-weight-heparin (LMWH) is an enhancement to the previous treatment due to its higher bioavailability and fewer side effects. Vitamin K antagonists (VKAs) are widely spread in medical environment thanks to their expanded mechanism of action, oral administration and reversibility of their overdose, as well as their well-developed anti-side effect therapy. Novel Oral Anticoagulants (NOACs) have been introduced to the market about 10 years ago. In spite of NOACs short period of clinical use, they were a huge change to the previous treating methods. Currently, the newest innovation in anticoagulant therapy are inhibitors of factor XI and its clinical trials outcome is promising for the future.Summary: The present article discusses history of anticoagulant drugs, their mechanism of action and usage but also focuses on the recent perspectives and developments as new anticoagulant drugs are being put to the test in therapeutic trials. The review underlines the importance of improvements in old therapeutic methods and exploring the new, more suitable ones.

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis. [ABSTRACT FROM AUTHOR]

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring. [ABSTRACT FROM AUTHOR]

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis characterized by the presence of vascular immunoglobulin A deposition that usually presents as non-thrombocytopenic palpable purpura. It primarily affects children and is less common in adults. The incidence of hemorrhagic necrotic skin lesions increases with age, similarly to renal involvement. Warfarin is a widely used oral anticoagulant drug that has rarely been associated with leukocytoclastic vasculitis and allergic interstitial nephritis. We report a patient with HSP who presented with cutaneous ulcerative plaques and proteinuria in the setting of warfarin therapy. We would like to raise the awareness of this potential adverse effect of warfarin for prompt diagnosis.

[Display omitted] [ABSTRACT FROM AUTHOR]

Antiplatelet and anticoagulant therapy are required in the treatment of peripheral arterial disease (PAD) to prevent thrombosis and maintain vascular patency, and the selection of an appropriate antiplatelet and anticoagulant therapy strategy is essential to ensure efficacy and clinical prognosis. This paper summarizes and analyzes the antiplatelet and anticoagulant therapy regimens and clinical research results of PAD at home and abroad. New regimen of antiplatelet drugs combined with anticoagulant drugs in patients with PAD is significantly better than traditional antiplatelet or anticoagulant therapy alone, without increasing the risk of bleeding. The emerging antiplatelet combined with anticoagulant therapy (aspirin + rivaroxaban) is currently the safest and most effective treatment strategy, and patients can benefit the most, marking a new era of PAD treatment mode. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Reconstructive Urology is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Patients using anticoagulant and/or antiplatelet (AC/AP) medications are at an increased risk of intracranial hemorrhage (ICH) subsequent to head trauma and current guidelines recommend a head computed tomography (CT) scan for these patients. There is a lack of consensus about management recommendations for mild head trauma patients on AC/AP treatment who had an initially normal head CT. The aim of this study was to determine the rate of delayed ICH after a 24-hour observation in patients with mild head trauma using AC/AP who had an initially normal head CT. Method: Patients aged 18 and older, using AC/AP drugs with mild head trauma were included prospectively. Patients underwent head CT for suspected bleeding. A repeat CT scan was performed after a 24-hours observation period for the patients who had an initially normal head CT for detecting delayed intracranial hemorrhage. Results: A total of 101 patients were included and, 57.4% (n=58) of the patients were female. Delayed ICH was detected in 2.9% (n=3) of the patients after a 24-hour observation. None of the patients with delayed ICH needed surgical treatment or further intervention. Delayed ICH was found in patients who used acetylsalicylic acid (n=1), dabigatran (n=1), and apixaban (n=1). Conclusion: In patients with mild head trauma using AC/AP, delayed intracranial hemorrhage is rare and may be clinically insignificant. A repeat CT scanning after 24-hour observation may not be necessary for patients with mild head trauma using AC/AP therapy who had initially normal head CT. [ABSTRACT FROM AUTHOR]

Objectives: Patients on anticoagulant medications may be at a higher risk of bleeding after acupuncture. This study aimed to assess the association between anticoagulant drug use and bleeding after acupuncture. Design: Case control study Setting: We analysed the diagnosis and treatment records (2000–2018) of a random sample of two million patients from the National Health Insurance Research Database in Taiwan. Interventions: anticoagulant and antiplatelet drugs Main outcome measures: The incidence rates of major (visceral bleeding or ruptured blood vessels requiring transfusion) and minor (skin bleeding or contusion) bleeding after acupuncture Results: We included the records of 13,447,563 acupuncture sessions in 821,946 participants and followed up the patients for 14 days after each session. The incidence of minor bleeding was 8.31 per 10,000 needles, whereas that of major bleeding was 4.26 per 100,000 needles. Anticoagulants significantly increased the risk of minor bleeding (adjusted OR = 1.15 (1.03–1.28)), but the risk of major bleeding did not reach statistical significance (adjusted OR = 1.18 (0.8 0–1.75)). Anticoagulants, such as warfarin (adjusted OR = 4.95 (2.55–7.64)), direct oral anticoagulants (adjusted OR = 3.07 (1.23–5.47)), and heparin (adjusted OR = 3.72 (2.18–6.34)) significantly increased the risk of bleeding. However, antiplatelet drug was not significantly associated with post-acupuncture bleeding. Comorbidities including liver cirrhosis, diabetes, and coagulation defects, were the risk factors for bleeding after acupuncture. Conclusions: Anticoagulant drugs may increase the risk of bleeding after acupuncture. We encourage physicians to ask patients in detail about their medical history and drug use prior to acupuncture treatment.

Atrial fibrillation (AF) is a life-changing and life-threatening cardiac electropathological condition, especially in patients with prior history of cardiovascular diseases. This multifaceted condition is one of the top 5 leading causes of cardiovascular death with a rapidly increasing prevalence and death rate. From inception till now, numerous clinical trials have been conducted to explore novel therapeutic targets and strategies along with pre-existing treatments for patients suffering from atrial fibrillation. The pharmacotherapy approach to treat AF (acute, chronic, persistent, paroxysmal, non-valvular, nonrheumatic, and rapid) comprises mainly antiarrhythmic drugs (AAD) and anticoagulant drugs (ACD) for rate and rhythm control along with the prevention of strokes. This narrative review aims to discuss monotherapeutic clinical trials that compared AADs (class II: carvedilol and xamoterol; class III: amiodarone; class IV: verapamil, diltiazem, and nifedipine) and ACDs (vitamin K antagonist: warfarin; factor Xa inhibitor: apixaban; factor IIa and Xa inhibitor: heparin) with cardiac glycoside (digoxin), angiotensin II receptor antagonist (telmisartan), platelet inhibitor (indobufen), anti-convulsant (magnesium sulfate), anti-inflammatory (aspirin), and antipyretic drugs (aspirin) to treat various types of AF in patients with a diverse history of cardiovascular diseases. This study provides a review of all clinical trials on this topic and provides a comparative chart for healthcare professionals to determine the best-suited treatment for their patients.

Anticoagulant drugs antagonize coagulation and are used to prevent or cure (recurrent) venous thromboembolism (VTE). Drugs to prevent clotting have been used for more than a century, and, nowadays, physicians possess a broad panel of multiple anticoagulants to meet the individual needs of a patient. Within this review, we aimed to revise the history of the different anticoagulants that are currently prescribed in the clinic. In addition, we compared their pharmacological properties, medical indications, and the difficulties in implementing new anticoagulants in vulnerable patient populations. Since the introduction of unfractionated heparin in the 1930s, major advances in the mechanistic understanding and the medical use of anticoagulants have allowed for significant improvements to treat VTE patients. However, a new generation of anticoagulants is currently being tested in clinical trials, with the goal of further optimizing medical care. [ABSTRACT FROM AUTHOR]

Background: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400–600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. Methods: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. Results: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman's test p < 0.01). For comparisons the Bland–Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. Conclusion: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions. [ABSTRACT FROM AUTHOR]

Objective: Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data. Methods: We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018. Results: Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE. Conclusion: This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE. [ABSTRACT FROM AUTHOR]

From 1800, arterial thrombosis and venous thrombosis were increasingly recognised as causes of sudden death. By 1960, they had replaced infections as the commonest cause of death in Scotland and the UK, as in many developed countries. The important contributions of Scotland's doctors between 1800 and 1960 to the knowledge of thrombosis, and to its treatment and prevention by anticoagulant drugs, are reviewed. [ABSTRACT FROM AUTHOR]

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.

This review provides an update on the different therapeutic approaches that have been used to treat SARS-CoV-2 infection, as well as, the resulting paradoxical inflammation disorders.

Introduction. Warfarin is one of the most frequently used anticoagulant agents in the clinic. The most important adverse effect of warfarin is hemorrhage of vital organs, such as lung and brain. Diffuse Alveolar Hemorrhage (DAH) is a rare clinical condition which occurs due to variety of medical disorders. Although it’s rarely reported, DAH can be a result of coagulopathy prompted by warfarin therapy. In this study we present a case of DAH, caused by warfarin toxicity which referred to the hospital with non-specific respiratory symptoms.

To evaluate major bleeding in cirrhosis with use of traditional anticoagulation or direct oral anticoagulants (DOACs), using a standardized definition. Anticoagulation in patients with cirrhosis is often a clinical conundrum for providers as the necessary balance between thrombotic and bleeding risk is complicated by end organ damage. Recent meta-analyses have sought to evaluate the safety and efficacy of direct oral anticoagulants in patients with liver disease. These recent analyses are limited by various bleeding definitions, broad inclusion criteria, and few indications for anticoagulation. We sought to conduct a meta-analysis using a validated definition for major bleeding and compare rates between traditional anticoagulation and DOACs in patients with cirrhosis. Articles were eligible for inclusion if the international society on thrombosis and hemostasis (ISTH) definition of a major bleed was the primary safety outcome. Additionally, only articles including patients with cirrhosis and receiving treatment with anticoagulation for an indication for stroke prevention or venous thromboembolism were eligible. Eligible articles needed a DOAC comparator group against traditional anticoagulant medication. Seven studies met inclusion criteria and compiled data for 683 patients in the meta-analysis. Pooled trial analysis demonstrated no statistically significant difference in the primary outcome of ISTH major bleeding (OR 0.55, 95%CI 0.28–1.07, I2 0%). Individual secondary outcomes of all bleeding, intracerebral hemorrhage, or gastrointestinal bleeding also demonstrated no significant difference between DOACs and traditional anticoagulation. Use of DOACs in patients with mild to moderate cirrhosis carries similar risk to use of traditional anticoagulation. [ABSTRACT FROM AUTHOR]

Anticoagulant drugs antagonize coagulation and are used to prevent or cure (recurrent) venous thromboembolism (VTE). Drugs to prevent clotting have been used for more than a century, and, nowadays, physicians possess a broad panel of multiple anticoagulants to meet the individual needs of a patient. Within this review, we aimed to revise the history of the different anticoagulants that are currently prescribed in the clinic. In addition, we compared their pharmacological properties, medical indications, and the difficulties in implementing new anticoagulants in vulnerable patient populations. Since the introduction of unfractionated heparin in the 1930s, major advances in the mechanistic understanding and the medical use of anticoagulants have allowed for significant improvements to treat VTE patients. However, a new generation of anticoagulants is currently being tested in clinical trials, with the goal of further optimizing medical care.

Venous thromboembolism (VTE) includes the diagnosis of either deep venous thrombosis (DVT) and/or pulmonary embolism (PE). This review discusses an evidence-based approach to the outpatient treatment of VTE in the emergency care setting. Main findings: The majority of patients diagnosed with VTE in the acute care setting are at low risk for an adverse event. Outpatient treatment for patients deemed low-risk by validated clinical decision tools leads to safe, efficacious, patient-centered, and cost-effective care. From a patient perspective, outpatient treatment of VTE can been simplified by the use of direct oral anticoagulant (DOACs) medications, and is supported by clinical trial evidence, and clinical practice guidelines from international societies. Outpatient treatment of patients with DVT has been more widely accepted as a best practice, while adoption of outpatient treatment of low-risk patients with acute PE has lagged. Many acute care clinicians remain wary of discharging patients with PE, concerned about drug access, adherence, and follow-up. Patients with VTE should be risk stratified identically as emerging evidence has demonstrated efficacy and safety in the interdependence of acute care protocols for the outpatient treatment of low-risk DVT and PE. Clinicians who practice in the acute care setting should be comfortable with risk stratification, anticoagulation, and discharge of low-risk VTE. [ABSTRACT FROM AUTHOR]

Introduction: Warfarin's narrow therapeutic index and high variability in dosage requirements make dosage selection critical. Genetic factors are known to impact warfarin dosage selection. The Hmong are a unique Asian subpopulation numbering over 278,000 in the United States whose participation in genetics‐based research is virtually nonexistent. The translational significance of early reports of warfarin pharmacogene differences in Hmong has not been evaluated. Objectives: (i) To validate previously identified allele frequency differences relevant to warfarin dosing in Hmong versus East Asians and (ii) to compare predicted warfarin sensitivity and maintenance doses between a Hmong population and an East Asian cohort. Method: DNA collected from two independent cohorts (n=236 and n=198) of Hmong adults were genotyped for CYP2C9 (*2, *3), VKORC1 (G‐1639A), and CYP4F2 (*3). Allele frequencies between the combined Hmong cohort (n=433) and East Asians (n=1165) from the 2009 International Warfarin Pharmacogenetics Consortium (IWPC) study were compared using a χ2 test. Percentages of Hmong and East Asian participants predicted to be very sensitive to warfarin were compared using a χ2 test, and the predicted mean warfarin maintenance dose was compared with a t test. Results: The allele frequencies of CYP2C9*3 in the combined Hmong cohort and CYP4F2*3 in the VIP‐Hmong cohort are significantly different from those in East Asians (18.9% vs 3.0%, p<0.001 and 9.8% vs 22.1%, p<0.001, respectively). Comparing the combined Hmong cohort to the East Asian cohort, the percentage of participants predicted to be very sensitive to warfarin was significantly higher (28% vs 5%, p<0.01) and the mean predicted warfarin maintenance dose was significantly lower (19.8 vs 21.3 mg/week, p<0.001), respectively. Conclusion: The unique allele frequencies related to warfarin when combined with nongenetic factors observed in the Hmong translate into clinically relevant differences in predicted maintenance dose requirements for Hmong versus East Asians. [ABSTRACT FROM AUTHOR]

Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs), considered as similar clinically, have administration differences useful for treatment individualization. Preferences, priorities and satisfaction of DOAC users were assessed through an observational, multicentric (25 hospitals), cross-sectional study including adult AF-patients (and/or caregivers) in Spain. Three study groups were considered according to DOAC posology preferences: (A) once-daily, with water; (B) once-daily, with food; (C) twice-daily. Overall, 332 patients and 55 caregivers were included. Mean (SD) age was 73.7 (10.7) years [58.7 (13.9) for caregivers]; 51.5% women [69.1% for caregivers]; 80.7% showed comorbidities and poly-pharmacy [6.6 (3.3) drugs/day]. No statistically significant differences were shown among study groups. Once-daily administration was preferred by 274 patients (82.5%) [60.8% (Group A); 21.7% (Group B); 17.5% (Group C)], and 47 caregivers (85.5%) [58.2% (Group A); 27.3% (Group B); 14.5% (Group C)]. Once-daily DOACs were prescribed in 42.8% of the patients. Bleeding risk was the main concern for both, patients and caregivers, followed by DOAC posology and interactions. Although treatment satisfaction (patients and caregivers) was high (9.0 and 9.1 points, respectively), match between individual treatment preferences and real prescriptions was only shown in 41.0% of AF-patients, evidencing a need for patient involvement on treatment decision-making. There is not a patient profile linked to treatment preferences, and clinical criteria must be the main driver for decision-making. However, for most AF-patients (elderly patients), aged, with comorbidity, poly-pharmacy and high cardiovascular risk, once-daily DOACs would be the preferred option. [ABSTRACT FROM AUTHOR]

OBJECTIVE: From the beginning of the novel coronavirus infection (COVID-19) pandemic in the world, much efforts have been accomplished to explain a precise clinical feature for the disease and to find the best therapeutic approach for the patients. Although coagulation abnormalities have found in novel coronavirus infection (COVID-19) patients, still little is known about the association between the disease and changes in coagulation parameters. Our purpose is to evaluate the differences between the coagulation parameters between COVID-19 patients and healthy counterparts. PATIENTS AND METHODS: 63 patients with confirmed COVID-19 infection were admitted to the present study. We evaluated coagulation value in these patients and in 40 healthy individuals. RESULTS: We found that although there was no significant difference between PT and PTT values in patients and healthy counterparts, the fibrinogen values in patients were higher than the control group (p < 0.05). Moreover, the values of fibrin/fibrinogen degradation products (FDP) and D-dimer in all COVID-19 cases were considerably higher than those in control people (p < 0.05). Of note, FDP and D-dimer in patients with regular COVID-19 infection were lower than patients with severe forms. CONCLUSIONS: It seems that the conduction of routine blood coagulation test could be a beneficial supplementary approach for early diagnosis of COVID-19. In addition, our study shed more light on the therapeutic value of anti- coagulant-based treatment for COVID-19 patients, especially for those with severe type of the disease. [ABSTRACT FROM AUTHOR]

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In rehabilitation medicine, attention must be paid to the medication. Among them, antithrombotic drugs are used for the initial treatment and secondary prevention of stroke, so as a basic knowledge, the pharmacological actions, characteristics, indications, and precautions for the use of antithrombotic drugs should be known. Antithrombotic agents are divided into antiplatelet agents and anticoagulants, and the appropriate antithrombotic agent is selected according to the main disease or condition. Antiplatelet agents include aspirin, clopidogrel, ticlopidine, prasugrel, ticagrelor, and cilostazol. Each antiplatelet agent has a different mechanism of action, characteristics, and indications, and should be prescribed with due consideration. Anticoagulants include heparin, synthetic Xa inhibitors, direct oral anticoagulants (DOACs), synthetic antithrombin agents, and warfarin. Knowledge of the mechanism of action, characteristics, and indications of each anticoagulant is necessary, as well as monitoring and dose adjustment. With regard to ischemic cerebrovascular disease (ICD) and antithrombotic agents, the first step is to classify cerebral infarction and to determine whether antiplatelet agents or anticoagulants should be used. Bleeding and recurrence prevention are important considerations in the selection of appropriate antithrombotic agents for the pathophysiology of ICD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Matsumoto et al.)

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up.Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change.Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence.Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.

Objective: Thermal Nd:YAG laser energy is well known for the purpose of blood coagulation. However, little is known about the bleeding frequency following laser-assisted oral surgery in patients on coumarin drugs. Therefore, the purpose of this study was to compare retrospectively the frequency of bleeding complications following Nd:YAG laser-assisted versus conventional local coagulation of blood In oral surgery. Method and Materials: In October 2002, minor oral surgical interventions were found to be indicated in a total of 45 cardiac risk patients. In Group 1, blood coagulation was yielded in 24 patients with a Nd:YAG laser system, whereas in Group 2, treatment was performed in 21 patients with conventional means of local hemostasis. All therapies were performed continuing anticoagulant therapy between November 2002 and March 2003. Clinical data were recorded retrospectively from patient charts in May 2007. Results: In both Groups 1 and 2, a total of two bleeding complications were recorded. However, local re-interventions were sufficient for local hemostasis. Conclusion: These results indicate that Nd:YAG laser-assisted local hemostasis was not able to prevent bleeding complications completely. Within the limitations of this retrospective study it was concluded that in patients with anticoagulant treatment undergoing minor oral surgery, Nd:YAG laser-assisted local hemostasis is not superior to conventional methods of blood coagulation with respect to the frequency of bleeding complications. [ABSTRACT FROM AUTHOR]

Marco Proietti,1–3 Giuseppe Boriani4 1Department of Neuroscience, IRCCS – Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy; 2Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK; 3Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy; 4Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy Abstract: Use of non-vitamin K antagonist oral anticoagulants is spreading in the real world. Despite that, a strong need for antidotes/reversal agents is still reported by several physicians. Idarucizumab is a humanized monoclonal antibody fragment that binds specifically to dabigatran. Idarucizumab was approved in 2015 by the US Food and Drugs Administration and European Medicines Agency for reversal of anticoagulation activity in dabigatran-treated patients. This review briefly summarizes the experimental evidence about effectiveness and safety of idarucizumab. Furthermore, we review the current recommendations and experts’ point of view about the use of antidotes/reversal agents in patients reporting a major bleeding event. Keywords: anticoagulant drugs, non-vitamin K antagonist oral anticoagulants, reversal agents, idarucizumab, major bleeding

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence. [ABSTRACT FROM AUTHOR]

Background: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.Methods: The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.Results: Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.Conclusions: A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984. [ABSTRACT FROM AUTHOR]

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Introduction: COVID-19-related thrombotic events are associated with an increase in the risk of mortality and morbidity. Considering the research on the pathophysiology of the disease, the significance of cardiac thrombosis is being more recognized. Case Presentation: This study aimed to present the first case report of a Left Main Coronary Artery (LMCA) thrombosis due to COVID-19 infection in a middle-aged male with a mechanical valve on anticoagulant therapy and with an International Normalized Ratio (INR) within the therapeutic range. Conclusions: The results suggested that the therapeutic INR range may need to be higher (about 3.5) during the acute phase of COVID-19 infection to prevent thrombotic events amongst patients with COVID-19 who are on anticoagulant therapy. However, further evidence is required to determine the target range for INR in patients with COVID-19 who are on anticoagulants prior to infection. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) is an important and common cardiovascular risk factor. The purpose of the study was to evaluate the frequency of use of oral antiplatelet drugs (OAPs) and oral anticoagulant drugs (OACs) among the elderly with T2DM in Poland. Material and methods: The study was based on the data collected in the Polish national PolSenior study. Results: Among 4979 PolSenior participants aged 65 and over, 883 (17.8%) had previously diagnosed T2DM. Among them, 441 (49.9%) used at least one drug in pharmacological cardiovascular prevention, i.e. OAPs (mostly ASA) in 405 (45.9%) cases and OACs in 38 (4.3%). The use of these drugs significantly depended on the sex (p = 0.02) and personal income (p = 0.05). Age, place of residence and level of education did not affect the prevalence of pharmacological prevention. Previous stroke and myocardial infarction were mostly associated with OAPs, whereas a history of atrial fibrillation (AF) was related to OAC treatment. Among participants treated with OAPs, therapy was applied as secondary cardiovascular prevention in 211 (52.1%) subjects, and as primary prevention in 194 (47.9%) subjects. Among participants treated with OACs, 24 (64.9%) persons had a history of AF. Secondary cardiovascular pharmacological prevention should be considered in 45 untreated participants (12.5%), and primary cardiovascular pharmacological prevention (SCORE ≥ 10 and/or AF) in 154 participants (42.7%). Conclusions : Cardiovascular pharmacological prevention in the elderly with T2DM in Poland seems to be unsatisfactory. Educational programmes concerning current recommendations for pharmacological cardiovascular prevention should be developed among general practitioners.

Herbal medicine is usually safe and popular in Iranian communities. Peppermint herbal products may interact with warfarin, which is an essential lifelong drug used in patients with prosthetic heart valves. Herein, we report a case of possible interaction between warfarin and peppermint herbal tea.We described a 68-year-old woman who was on warfarin treatment due to bileaflet mechanical aortic valve, and mitral valve replacement presented with severe dyspnea in the setting of large obstructive prosthetic mitral valve thrombosis diagnosed by echocardiography. Therefore, cardiac surgery was conducted in the emergent setting. Warfarin was started the day after the procedure. She developed melena with a volatile and elevated international normalized ratio (INR) of 4.8 and prothrombin time > 30 s on the 7th post-operation day. She reported no changes in drug or dietary habits except for drinking high amounts of peppermint tea the day before. After the discontinuation of warfarin and medical consultation for gastrointestinal bleeding, the INR level decreased to 1.8 within two days.Consumption of peppermint herbal products are usually safe; however, caution should be taken with patients under warfarin treatment. Full disclosure for patients on anticoagulant treatment is necessary before discharge and during clinical follow-up

Most of the unfractionated heparin (UFH) consumed worldwide is manufactured using porcine mucosa as raw material (HPI); however, some countries also employ products sourced from bovine mucosa (HBI) as interchangeable versions of the gold standard HPI. Although accounted as a single UFH, HBI, and HPI have differing anticoagulant activities (~100 and 200 IU mg−1, respectively) because of their compositional dissimilarities. The concomitant use of HBI and HPI in Brazil had already provoked serious bleeding incidents, which led to the withdrawal of HBI products in 2009. In 2010, the Brazilian Pharmacopeia (BP) formed a special committee to develop two complementary monographs approaching HBI and HPI separately, as distinct active pharmaceutical ingredients (APIs). The committee has rapidly agreed on requirements concerning the composition and presence of contaminants based on nuclear magnetic resonance and anion-exchange chromatography. On the other hand, consensus on the anticoagulant activity of HBI was the subject of long and intense discussions. Nevertheless, the committee has ultimately agreed to recommend minimum anti-FIIa activities of 100 IU mg−1 for HBI and 180 IU mg−1 for HPI. Upon the approval by the Brazilian Health Authority (ANVISA), the BP published the new monographs for HPI and HBI APIs in 2016 and 2017, respectively. These pioneer monographs represent a pivotal step toward the safest use of HBI and HPI as interchangeable anticoagulants and serve as a valuable template for the reformulation of pharmacopeias of other countries willing to introduce HBI.

Lack of INR controls might affect the adherence to direct oral anticoagulants (DOAC). The vast majority of studies that addresses adherence to anticoagulants are retrospective and based on pharmacy refill data. Our aim was to compare the adherence between vitamin K antagonists (VKA) and DOAC and to analyze the clinical relevance of non-adherence. A prospective two-arm observational cohort study was performed in two Spanish public hospitals. Adherence was assessed by Medication Event Monitoring System. Relationship between adherence and events during follow-up and time in therapeutic range (TTR) in the VKA group were analyzed. 257 patients were included (132 DOAC and 125 VKA). Monitoring time was 120 days (101−133). Patients in VKA group showed higher taking adherence (97.9% vs. 95.8%) and less non-adherent patients of >5% and >10% of the doses, without differences in >20% of the doses. Taking adherence was strongly associated with TTR (AUC: 0.89, CI 95%: 0.81–0.97 of TTR for detection of non-adherent patients of >10% of doses). During a follow-up of 1.8 years (1.6–2) non-adherent patients of >5% of doses presented more thromboembolic events (HR 6.1, CI95% 1.3–28.1). Although adherence to oral anticoagulant therapy was excellent, it was higher to VKA than to DOAC. Time in therapeutic range was highly sensitive to few missed doses of AVK. Non-adherence of >5% of prescribed doses had high clinical relevance. • Lack of INR controls could affect adherence to direct oral anticoagulants (DOAC). • Medication Event Monitoring System was used to compare adherence between both anticoagulants. • Adherence was very high, slightly better to vitamin K antagonists than to DOAC. • Missing even a few doses was related to poor INR control and had high clinical relevance. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence and endovascular treatment of severe spontaneous non-cerebral hemorrhage (SSNCH) in a high-volume, tertiary university hospital.Methods: All patients diagnosed with SSNCH between January 2016 and June 2017 were retrospectively analyzed. Endovascular treatment (group EVT) was offered only in patients demonstrating active bleeding at CT angiography (CTA). In cases without active bleeding at CTA, conservative management was decided (group CM). Outcome measures included the incidence of SSNCH, 6-month rebleeding, and survival rates in the two groups as well as EVT technical success and related complications.Results: Within the 18-month period, 44 SSNCH cases were identified, resulting in an annual incidence of 29.3 cases. In 37/44 cases (84.1%), bleeding was attributed to the antithrombotic therapy. In total, 19/44 patients underwent EVT (43.2%), and 25/44 patients (56.8%) were managed conservatively. Two patients who were initially treated conservatively finally underwent EVT due to rebleeding (7.4%). The technical success of EVT was 100%, while rebleeding occurred in 1 case (5.2%) following lumbar artery embolization and was successfully re-embolized. According to the Kaplan-Meier analysis, the 1-, 3-, and 6-month survival rates were 68.4%, 63.2%, and 42.1% for group EVT and 87.5%, 75.0%, and 58.3% for group CM, respectively. There were no EVT-related complications.Conclusions: The annual incidence of SSNCH in our institution is substantial. EVT resulted in uncomplicated, high bleeding control rates. The mortality rate was similarly high following either EVT or conservative treatment and was mainly attributed to severe comorbidities.Key Points: • This study demonstrates that the incidence of severe spontaneous non-cerebral hemorrhage (SSNCH) in our institution is substantial. • Endovascular treatment was offered only in patients with clinical signs of ongoing hemorrhage and active bleeding at CT angiography and resulted in effective and uncomplicated, minimal invasive hemostasis, in a population with severe comorbidities. • This is the first study to evaluate the outcomes of both endovascular hemostasis and conservative management. Rebleeding following either conservative or endovascular treatment was minimal. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive overview of the available data on antithrombotic therapy after transcatheter aortic valve implantation (TAVI). In the absence of large randomised clinical trials, clinical practice is leaning towards evidence reported in other populations. Due to the greater risk of major bleeding associated with oral anticoagulation using a vitamin-K antagonist (VKA), antiplatelet therapy (APT) may be considered as the first-line treatment of patients undergoing TAVI. Overall, single rather than dual APT is preferred. However, dual APT should be considered in patients with a recent acute coronary syndrome (ie, within 6 months), complex coronary stenting, large aortic arch atheromas or previous non-cardioembolic stroke. Monotherapy with VKA should be considered if concomitant atrial fibrillation or any other indication for long-term oral anticoagulation is present. APT on top of VKA seems only reasonable in patients with recent acute coronary syndrome, extensive or recent coronary stenting or large aortic arch atheromas. A direct-acting oral anticoagulant may be considered if oral anticoagulation is indicated in the absence of contraindications. Initiation of VKA is indicated in clinical valve thrombosis, for example, with high transvalvular gradient, whereas the role of VKA in the case of subclinical leaflet thrombosis is currently uncertain. [ABSTRACT FROM AUTHOR]

Abstract A sensitive technique for the measurement of warfarin and its metabolic enantiomers in human fluids such as urine and serum technique was developed by applying ultrasound-assisted dispersive liquid-liquid microextraction linked with poly(ethylene oxide)-mediated stacking in capillary electrophoresis. The parameters that influence extraction and stacking performance-the type of the extraction and dispersive solvents and their volume, extraction time, salt additives, sample matrix, solution pH, and the composition of background electrolyte stacking-were carefully studied and optimized based on the considering of obtaining the best detection sensitivity. Under the optimal extraction (30 μL C 2 H 2 Cl 4 and 200 μL tetrahydrofuran in 1 mL of sample solution) and separation (0.5% PEO, 200 mM Tris-borate, pH 8.5, and 5 mM dimethyl-β-cyclodextrin) conditions, the enrichment factors of D-/L-warfarins and D-/L-7-OH warfarins covered from 1758 to 1859 and their limits of detection ranged from 0.34 to 0.38 nM. Calibration-related results exhibited acceptable linearity with the coefficient of determination higher than 0.99; the relative standard deviations of the peak area were determined to 4.1%–6.3% (n = 3). The recovery of four separated analytes spiked in samples of urine and serum was found to be 93%–110% and 95%–109%, respectively. We revealed that ultrasound-assisted dispersive liquid-liquid microextraction with poly(ethylene oxide)-mediated stacking in capillary electrophoresis could be a prompt and practical method for quantifying the levels of warfarin and its metabolic enantiomers in real-world samples, especially in biological fluids. Highlights • A enantiomer separation combined DLLME and CE for determination of warfarin and its metabolic enantiomers. • Detection of two pairs of warfarin and its metabolic enantiomers in nM concentration were achieved. • This method was applied for detecting warfarin and its metabolites enantiomers drugs in urine and plasma. [ABSTRACT FROM AUTHOR]

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case–control study using Danish demographic and health data registries and summarized existing evidence in a meta‐analysis. The case–control study included all Danish men aged 40–85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age–matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long–term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95–1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97–1.10). We observed no dose–response relationship (e.g. OR for 5–10 years of use, 1.06 95% CI, 0.97–1.16). We included 8 studies in the meta–analysis reporting effect estimates from 0.51 (95% CI, 0.23–1.13) to 1.10 (95% CI, 0.94–1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70–1.05) was obtained; however, there was considerable across–study heterogeneity (I2: 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely. What's new? Vitamin K antagonists potentially exert antineoplastic effects on prostate cancer cells and may reduce prostate cancer risk. However, findings from observational studies are conflicting. In the present nationwide study of incident prostate cancers among men in Denmark from 2005–2015, the authors found no evidence linking long–term use of vitamin K antagonists, specifically warfarin and phenprocoumon, to prostate cancer risk. In a systematic review and meta‐analysis, the authors reported a high degree of heterogeneity among existing studies. In conclusion, the available evidence did not support a major protective effect of vitamin K antagonists against prostate cancer. [ABSTRACT FROM AUTHOR]