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Translational Research : the Journal of... Nov 2020Antiphospholipid syndrome is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous, or microvascular)... (Review)
Review
Antiphospholipid syndrome is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous, or microvascular) and pregnancy morbidity (miscarriages, late intrauterine fetal demise, and severe pre-eclampsia). Classification criteria include 3 different antiphospholipid antibodies: lupus anticoagulant, anticardiolipin, and anti-beta 2 glycoprotein I. Management includes both preventive strategies (low-dose aspirin, hydroxychloroquine) and long-term anticoagulation after thrombosis.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans
PubMed: 32413497
DOI: 10.1016/j.trsl.2020.04.006 -
Hamostaseologie Feb 2022Antiplatelet and anticoagulant drugs work at different places in the coagulation system. Antiplatelet drugs are usually indicated in patients with atherosclerosis....
Antiplatelet and anticoagulant drugs work at different places in the coagulation system. Antiplatelet drugs are usually indicated in patients with atherosclerosis. Anticoagulant drugs are mostly used in patients with atrial fibrillation, venous thromboembolism, or technical heart valves. In some clinical situations, combination of antiplatelet and anticoagulant therapy can be indicated. The most recent situations are a more intensive antithrombotic therapy for risk reduction in patients with atherosclerosis and temporary addition of antiplatelet drugs in patients with indication for long-term anticoagulation. Temporary combination of antiplatelet and anticoagulant drugs is usually necessary after coronary intervention in patients with atrial fibrillation. In patients with high-risk atherosclerosis, the combination of low-dose rivaroxaban and aspirin reduces major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death) and major adverse limb events. But every combination of antiplatelet and antithrombotic drugs can increase bleeding risk. Therefore, a careful assessment of thrombotic versus bleeding risk is necessary for each patient.
Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors
PubMed: 35196733
DOI: 10.1055/a-1724-4922 -
Thrombosis Research Feb 2021Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid... (Review)
Review
Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid antibodies (aPL). The diagnosis and management of thrombotic APS continues to prove challenging for clinicians. We provide a practical guide to the diagnosis of APS including who to test for aPL and which tests to do. We also consider clinical practice points on the management of venous, arterial and small vessel thrombosis, in the context of first and recurrent thrombotic events. Non-criteria manifestations of APS are reviewed. An approach to recurrent thrombosis and anticoagulant-refractory APS is discussed, with options including increasing the anticoagulation intensity of vitamin K antagonists, switching to low-molecular-weight-heparin, the use of fondaparinux and/or the addition of antiplatelet treatment. Adjunctive options such as vitamin D, hydroxychloroquine and statins are also addressed.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Humans; Thrombosis
PubMed: 33485122
DOI: 10.1016/j.thromres.2020.10.010 -
Journal of Thrombosis and Haemostasis :... Apr 2021Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin... (Review)
Review
Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin or an alternative vitamin K antagonist. The role of direct oral anticoagulants for thrombotic APS is not established due to the lack of definitive evidence and has recently been addressed in international guidance. Other anticoagulant options include low molecular weight heparin, unfractionated heparin, and fondaparinux. In APS patients, lupus anticoagulant can affect phospholipid-dependent coagulation monitoring tests, so that they may not reflect true anticoagulation intensity. Accurate assessment of anticoagulation intensity is essential, to optimize anticoagulant dosing and facilitate thrombus resolution; minimize the risk of recurrent thrombosis or bleeding; inform assessment of whether recurrent thrombosis is related to breakthrough thrombosis while on therapeutic anticoagulation, subtherapeutic anticoagulation, non-adherence, or spurious results; and guide the management of bleeding. Knowledge of anticoagulant intensity also informs assessment and comparison of anticoagulation regimens in clinical studies. Considerations regarding anticoagulation dosing and/or monitoring of thrombotic APS patients underpin appropriate management in special situations, notably APS-related severe renal impairment, which can occur in APS or APS/systemic lupus erythematosus-related nephropathy or catastrophic APS; and APS-related thrombocytopenia. Anticoagulant dosing and monitoring in thrombotic APS patients also require consideration in anticoagulant-refractory APS and during pregnancy. In this review, we summarize the tests generally used in monitoring anticoagulant therapy, use of the main anticoagulants considered for thrombotic APS, lupus anticoagulant effects on anticoagulation monitoring tests, and strategies for appropriate anticoagulant monitoring in thrombotic APS.
Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Female; Heparin; Humans; Pregnancy; Thrombosis
PubMed: 33325604
DOI: 10.1111/jth.15217 -
The Western Journal of Emergency... Aug 2019Owing to the propensity of anticoagulated patients to bleed, a strategy for reversal of anticoagulation induced by any of the common agents is essential. Many patients... (Review)
Review
Owing to the propensity of anticoagulated patients to bleed, a strategy for reversal of anticoagulation induced by any of the common agents is essential. Many patients are anticoagulated with a variety of agents, including warfarin, low molecular weight heparin, and the direct oral anticoagulants such as factor Xa and factor IIa inhibitors. Patients may also be using antiplatelet agents. Recommendations to reverse bleeding in these patients are constantly evolving with the recent development of specific reversal agents. A working knowledge of hemostasis and the reversal of anticoagulation and antiplatelet drugs is required for every emergency department provider. This article reviews these topics and presents the currently recommended strategies for dealing with bleeding in the anticoagulated patient.
Topics: Anticoagulants; Emergencies; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Hemostatic Techniques; Humans; Platelet Aggregation Inhibitors
PubMed: 31539334
DOI: 10.5811/westjem.2018.5.38235 -
Cells Oct 2022Anticoagulant drugs antagonize coagulation and are used to prevent or cure (recurrent) venous thromboembolism (VTE). Drugs to prevent clotting have been used for more... (Review)
Review
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.
Topics: Humans; Anticoagulants; Venous Thromboembolism; Heparin; Blood Coagulation
PubMed: 36291080
DOI: 10.3390/cells11203214 -
Trends in Cardiovascular Medicine Jul 2022This review examines the recent progress in the initial management of pulmonary embolism (PE). Diagnostic strategies allowing the safe decrease of imaging testing have... (Review)
Review
This review examines the recent progress in the initial management of pulmonary embolism (PE). Diagnostic strategies allowing the safe decrease of imaging testing have been proposed. New modalities of catheter-based interventions have emerged for hemodynamically unstable PE patients. For normotensive PE patients, direct oral anticoagulant treatment has become the new norm and a large proportion of patients are eligible for home treatment.
Topics: Acute Disease; Anticoagulants; Humans; Pulmonary Embolism; Thrombolytic Therapy
PubMed: 34214598
DOI: 10.1016/j.tcm.2021.06.002 -
Trends in Cardiovascular Medicine Feb 2020Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial... (Review)
Review
Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.
Topics: Administration, Oral; Anticoagulants; Antidotes; Atrial Fibrillation; Blood Coagulation; Blood Loss, Surgical; Clinical Decision-Making; Coagulants; Drug Administration Schedule; Humans; Perioperative Care; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Venous Thromboembolism
PubMed: 30952383
DOI: 10.1016/j.tcm.2019.03.004 -
International Journal of Molecular... Feb 2022Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and... (Review)
Review
Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.
Topics: Administration, Oral; Anticoagulants; Antithrombins; Humans; Protein C; Risk Factors; Thrombophilia; Thrombosis; Venous Thromboembolism
PubMed: 35163742
DOI: 10.3390/ijms23031821 -
Clinical Pharmacokinetics Aug 2020A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of... (Review)
Review
A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug-disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing.
Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Humans; Renal Insufficiency
PubMed: 32157630
DOI: 10.1007/s40262-020-00879-x