Thrombosis pathways and therapeutic strategies

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Therapeutic Strategies ◽  
Coagulation Cascade ◽  
Bleeding Complications ◽  
Common Side Effect ◽  
Complex Disorders ◽  
Risk Of Bleeding

Thrombosis is the world's leading cause of death, accounting for one of everyfour deaths. Atrial fibrillation is responsible for around a tenth of all ischaemicstrokes (AF) Antiplatelet drugs are the cornerstone of AT treatment andprevention. Long-term use of aspirin and clopidogrel has little advantage overeither agent alone in terms of stroke prevention. It does, however, significantlyraise the risk of bleeding complications. Direct oral anticoagulants are at least aseffective as warfarin in reducing stroke. Return to the tab on which you arrived.Bleeding is the most common side effect of all commercially approvedantiplatelet drugs. Thrombin, thrombine, and thromboembolism are also bloodclotting proteins that are deficient in certain patients to differing degrees.Thrombin is a platelet activator that plays a role in platelet-coagulation pathwaycrosstalk. All coagulated factors, with the exception of FXII, are required forhaemostasis. Extrinsic and typical pathway components are required byhaemostases. The key protease in the coagulation cascade is thrombin. Since thehaemostatic plugs have sealed the wound, the fibrinolytic system separates themfrom the vasculature. Nanomedicine has elegantly attempted to cure differentgene polymorphisms and mutations in complex disorders using gene therapyapproaches.

scholarly journals Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prospective Trial ◽  
Bleeding Complications ◽  
Order Of Magnitude ◽  
Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexander C Perino ◽  
Krishna Pundi ◽  
Jun Fan ◽  
Susan K Schmitt ◽  
Mitra Kothari ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Warfarin Treatment ◽  
Treatment Analysis ◽  
Using Data ◽  
Favorable Safety

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Anticoagulation Regimens and Interventional Pain Procedures

2018 ◽  
Author(s):  
Christine Oryhan ◽  
Kevin Vorenkamp ◽  
Daniel Warren
Keyword(s):  
Chronic Pain ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patient Characteristics ◽  
The United States ◽  
Bleeding Complications ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Spinal Epidural ◽  
The Ideal

With the aging population and new anticoagulant medications, such as direct oral anticoagulants, being marketed in the United States, it is very important for pain physicians to be aware of the anticoagulants available and how they affect the safety of interventional pain procedures. In addition to anticoagulant and antiplatelet medications, other medications commonly used in the chronic pain population may put patients at increased risk of bleeding complications. Certain patient characteristics, particularly in the chronic pain population, may also increase a patient’s risk of bleeding. The chapter reviews common and emerging anticoagulant and antiplatelet medications and the ideal holding time before or after interventional pain procedures, particularly in the spine. The chapter also discusses the diagnosis, treatment, and outcomes of spinal epidural hematomas.

scholarly journals Type 2 Diabetes, Atrial Fibrillation, and Direct Oral Anticoagulation

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Dana Prídavková ◽  
Matej Samoš ◽  
Tomáš Bolek ◽  
Ingrid Škorňová ◽  
Jana Žolková ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Current Data ◽  
Thrombin Inhibitor

Type 2 diabetes (T2D) is an independent risk factor of stroke and systemic embolism in patients with atrial fibrillation (AF), and T2D patients with AF-associated stroke seem to have worse clinical outcome and higher risk of unfavorable clinical course compared to individuals without this metabolic disorder. Long-term anticoagulation is indicated in majority of T2D patients with AF to prevent adverse AF-associated embolic events. Direct oral anticoagulants (DOACs), direct oral thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have emerged as a preferred choice for long-term prevention of stroke in AF patients offering potent and predictable anticoagulation and a favorable pharmacology with low risk of interactions. This article reviews the current data regarding the use of DOACs in individuals with T2D and AF.

Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5014-5014 ◽  
Author(s):  
Kathryn E. Dickerson ◽  
Ravi Sarode ◽  
Ayesha Zia
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Case Series ◽  
Bleeding Complications ◽  
Fixed Dose ◽  
The Mean ◽  
Recurrent Vte

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties. Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA). Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed. Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

scholarly journals The risk of bleeding minimization with direct oral anticoagulants

2021 ◽  
pp. 106-126
Author(s):  
Т. N. Novikova
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Anticoagulant Therapy ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Blood Analysis ◽  
Systemic Embolism ◽  
Risk Of Bleeding ◽  
Wide Range

This review is devoted to the safety issues of anticoagulant therapy prescribed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Direct oral anticoagulants are considered worldwide in accordance with the guidelines for the diagnosis and treatment of atrial fibrillation as the preferred anticoagulant choice for the prevention of stroke and systemic embolism. Direct oral anticoagulants in comparison with vitamin K antagonists generally have similar efficacy, but different safety profiles, primarily, this concerns the risk of large extracranial and, primarily, gastrointestinal hemorrhages. To minimize the risk of bleeding during therapy with direct oral anticoagulants, an individual approach to the choice of the drug for each individual patient is required after assessing the risk of bleeding, searching for a potential bleeding substrate, correcting existing risk factors and eliminating, if possible, the substrate. When choosing an anticoagulant therapy, special attention should be paid to the most vulnerable categories of patients, such as patients of older age groups and patients with concomitant chronic kidney disease. Among the direct oral anticoagulants registered in the Russian Federation, according to meta-analyzes of key randomized clinical trials and real clinical trials, apixaban has the most optimal benefit: risk ratio in a wide range of patients, including vulnerable populations. Dynamic observation, including regular assessment of renal function, control of clinical blood analysis, erythrocyte and platelet levels, after prescribing an individually selected anticoagulant to the patient, ensures the maximum safety of therapy. Small, so-called, annoying bleeding is not a reason for canceling the anticoagulant, but requires a careful search for the causes of bleeding and their correction.

scholarly journals 286 Incidence of pocket haematoma with different anticoagulation strategies in patients undergoing cardiac implantable device implant or revision

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Enrico Guido Spinoni ◽  
Matteo Santagostino ◽  
Simona Costantino ◽  
Eleonora Battistini ◽  
Gabriele Dell’Era ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Multivariate Analysis ◽  
Propensity Score ◽  
Electronic Device ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Bleeding Complications

Abstract Aims Direct oral anticoagulants (DOACs) are known for lower bleeding risk than vitamin K antagonist (VKA) in patients with atrial fibrillation (AF). To date, it has not been established whether in such population DOAC may offer reduction of bleeding complication in patients undergoing cardiac implantable electronic device (CIED) implant or revision (substitution, upgrade, or downgrade). We evaluated whether DOACs compared to VKAs, decrease bleeding complications at the time of CIED implant in patients with AF, requiring oral anticoagulant therapy. Methods and results We present a monocentric observational retrospective study. Patients undergoing implant, generator replacement, or upgrading/downgrading of an intracardiac device (PM, ICD, or CRT) between January 2015 and March 2021 with AF undergoing DOAC or VKA were included. The comparison of risk of clinically significant pocket hematoma at 30-days follow-up in the two-treatment group [DOAC vs. VKA and DOAC vs. VKA without low molecular weight eparin (LMWH) bridge] was performed. Cox proportional hazards regression analysis including main clinical findings was performed to test the primary endpoint. Propensity score matching analysis was performed, with inversed proportional weighted (IPW) propensity score included in the multivariate analysis. 311 patients were included, 146 (46.9%) treated with DOAC and 165 (53.1%) treated with VKA. The incidence pocket haematoma was significantly reduced in patients treated with DOAC compared with VKA (3.4% vs. 13.3%, respectively, P = 0.002), a finding confirmed on multivariate analysis (HR: 3.02, CI: 1.10–8.29, P = 0.032). The incidence of pocket haematoma in patients on DOAC vs. VKA without LMWH bridge therapy was found to be significantly higher in the latter group of patients (P = 0.033, HR: 2.93, CI: 1.01–8.49, P = 0.48). After adjusting at propensity score with IPW, DOAC use showed decreased risk of pocket haematoma (HR: 0.29, CI: 0.09–0.95, P = 0.42). Conclusions In patients with atrial fibrillation undergoing CIED implant or revision, DOAC therapy appears to be associated with lower risk of event-related pocket haematoma at 30-day follow-up, even in the absence of bridging with LWMH. Such findings are hypothesis-generating.

scholarly journals Przewlekłe leczenie przeciwkrzepliwe

2018 ◽  
Vol 49 (2) ◽  
pp. 47-49 ◽  
Author(s):  
Krystyna Zawilska
Keyword(s):  
Pulmonary Embolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Compression Therapy ◽  
Good Choice ◽  
Anticoagulant Treatment ◽  
Efficacy And Safety ◽  
Risk Of Bleeding

AbstractUnprovoked venous thromboembolism (VTE) - proximal venous thrombosis or pulmonary embolism - should be treated either 3 months or indefinitely if the risk of bleeding is low. This article summarizes the efficacy and safety of extended therapy of VTE with direct oral anticoagulants (DOAC) in comparison with warfarin, as well as the role of of acetylsalicylic acid (ASA) for the long-term prevention of recurrent VTE. As the Survet study showed, for some patients who have already completed at least 6 months of anticoagulant treatment for their index VTE event, an oral glycosaminoglycan - sulodexide associated with compression therapy is a good choice, because it decreases the incidence of recurrences of VTE without detectable risks for the patients’ safety.

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