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Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.
Athanazio, RA, Ceresetto, JM, Marfil Rivera, LJ, Cesarman-Maus, G, Galvez, K, Marques, MA, Tabares, AH, Ortiz Santacruz, CA, Santini, FC, Corrales, L, et al
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2022;:10760296221082988
Abstract
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.
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2.
Anticoagulants for stroke prevention in heart failure with reduced ejection fraction.
Schäfer, A, Flierl, U, Bauersachs, J
Clinical research in cardiology : official journal of the German Cardiac Society. 2022;(1):1-13
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Abstract
Impaired left-ventricular ejection-fraction (LV-EF) is a known risk factor for ischemic stroke and systemic embolism in patients with heart failure (HF) even in the absence of atrial fibrillation. While stroke risk is inversely correlated with LV-EF in HF patients with sinus rhythm, strategies using anticoagulation with Vitamin-K antagonists (VKA) were futile as the increase in major bleedings outweighed the potential benefit in stroke reduction. Non-Vitamin K oral anticoagulants (NOACs) proved to be an effective and in general safer approach for stroke prevention in patients with atrial fibrillation and may also have a favourable risk-benefit profile in HF patients. In HF patients with sinus rhythm, the COMPASS trial suggested a potential benefit for rivaroxaban, whereas the more dedicated COMMANDER-HF trial remained neutral on overall ischemic benefit owed to a higher mortality which was not influenced by anticoagulation. More recent data from subgroups in the COMMANDER-HF trial, however, suggest that there might be a benefit of rivaroxaban regarding stroke prevention under certain circumstances. In this article, we review the existing evidence for NOACs in HF patients with atrial fibrillation, elaborate the rationale for stroke prevention in HF patients with sinus rhythm, summarise the available data from anticoagulation trials in HF with sinus rhythm, and describe the patient who might eventually profit from an individualised strategy aiming to reduce stroke risk.
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Oral Anticoagulant Use in Morbid Obesity and Post Bariatric Surgery: A Review.
Nasser, MF, Jabri, A, Gandhi, S, Rader, F
The American journal of medicine. 2021;(12):1465-1475
Abstract
Bariatric surgery has emerged as a therapy for obesity and the associated comorbidities. Obesity has been shown to be a risk factor for atrial fibrillation as well as venous thromboembolism, both of which are conditions that warrant anticoagulation. There is significant underrepresentation of the morbidly obese population in prospective trials that evaluated direct oral anticoagulants and vitamin K antagonists in atrial fibrillation and venous thromboembolism. We aim to review all the available data that assessed these oral anticoagulants in the morbidly obese population (body mass index >40 kg/m2 and weight >120 kg) and in the post-bariatric surgery population. Our findings suggest that direct oral anticoagulants may be safe and effective for anticoagulation in morbidly obese patients for both atrial fibrillation and venous thromboembolism. However, warfarin is the preferred agent in the post-bariatric surgery population, given the limited number of studies on direct oral anticoagulants in this population. Further adequately powered randomized control trials are needed to confirm the safety and efficacy of these oral anticoagulants in the morbidly obese and post-bariatric surgery population.
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Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome.
Carré, J, Jourdi, G, Gendron, N, Helley, D, Gaussem, P, Darnige, L
International journal of molecular sciences. 2021;(1)
Abstract
For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.
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Evidence-Based Minireview: Should warfarin or a direct oral anticoagulant be used in patients presenting with thrombosis in the splanchnic or cerebral veins?
Mathew, C, Zumberg, M
Hematology. American Society of Hematology. Education Program. 2021;(1):100-105
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Abstract
Case 1: A 23-year-old female third-year medical student who has no medical history seeks treatment for abdominal distention. She takes an estrogen-containing birth control pill and does not smoke or consume alcohol. Family history is unremarkable. Physical examination is significant for abdominal distention, and an abdominal fluid wave is detected. Complete blood count is normal. Imaging confirms occlusive thrombosis of the main portal vein. On endoscopy, grade 1 to 2 esophageal varices are noted and banded. Unfractionated heparin is begun. Subsequent workup reveals a homozygous factor V Leiden mutation. Long-term anticoagulation is planned, and she asks if warfarin can be avoided given her hectic ward rotations, erratic diet, and need for monitoring. Case 2: A 35-year-old woman who has no medical history seeks treatment for progressively worsening posterior headaches for 1 week. Magnetic resonance imaging of the brain shows dural sinus thrombosis with associated small areas of petechial cerebral hemorrhage. She is started on a continuous unfractionated heparin infusion and admitted to the hospital for further observation. Her grandmother is on warfarin for atrial fibrillation, and the patient would prefer to avoid warfarin because she does not think she can comply with the frequent monitoring that will be required. She inquires about other oral anticoagulant options for her condition.
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Treatment of portal vein thrombosis: an updated narrative review.
Caiano, LM, Riva, N, Carrier, M, Gatt, A, Ageno, W
Minerva medica. 2021;(6):713-725
Abstract
Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). Anticoagulant therapy in patients with acute symptomatic PVT should be started early after diagnosis, if no active bleeding, to obtain greater vessel recanalization and reduce the occurrence of portal-hypertension related complications. Gastroesophageal varices do not represent a contraindication to anticoagulant treatment, as long as adequate measures have been undertaken for the prophylaxis of gastroesophageal bleeding. Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarize recent guidelines on this topic.
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Anticoagulant Reversal in Gastrointestinal Bleeding: Review of Treatment Guidelines.
Milling, TJ, Refaai, MA, Sengupta, N
Digestive diseases and sciences. 2021;(11):3698-3714
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Abstract
BACKGROUND Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa). AIM: To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed. METHODS This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data. RESULTS GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio > 2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications. CONCLUSIONS The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios.
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Evidence-Based Minireview: Are DOACs an alternative to vitamin K antagonists for treatment of venous thromboembolism in patients with MPN?
Schieppati, F, Falanga, A
Hematology. American Society of Hematology. Education Program. 2021;(1):448-452
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Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment.
Gąsecka, A, Borovac, JA, Guerreiro, RA, Giustozzi, M, Parker, W, Caldeira, D, Chiva-Blanch, G
Cardiovascular drugs and therapy. 2021;(2):215-229
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Abstract
INTRODUCTION Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. PROPHYLAXIS, DIAGNOSIS AND TREATMENT COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients' clinical outcomes. RECOMMENDATIONS FOR CLINICIANS Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. CONCLUSIONS Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19.
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Anti-thrombotic strategies in patients with atrial fibrillation undergoing PCI.
Schäfer, A, Flierl, U, Bauersachs, J
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(6):759-774
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Triple anti-thrombotic therapy combining oral anticoagulation and dual anti-platelet therapy following percutaneous coronary intervention in patients with atrial fibrillation was considered as standard and recommended by guidelines. While bleeding risk is considerable with that approach, data for efficacy are scare. Several trials assessed the possibility of reducing anti-thrombotic treatment by mainly shortening the exposure to acetylsalicylic acid. Dropping one of the anti-platelet components might increase the risk of stent thrombosis, myocardial infarction or stroke. Despite that fear, the recent trials' primary endpoint was major and/or clinically-relevant non-major bleeding. We review data on major bleedings, intracranial bleedings and major adverse cardiovascular events from the published reports. We demonstrate that Non-Vitamin K oral anticoagulant (NOAC)-based strategies compared to VKA-based triple therapies significantly reduce the risk for TIMI-major bleedings by 39% and for intracranial bleedings by 66%, while they did not increase the risk for overall ischemic or embolic events. However, recent meta-analyses indicate an increased risk for stent thrombosis with less intense anti-thrombotic therapy. While the overall incidence rate for stent thrombosis is rather low, relative increases by about 30-60% are reported, but they did not translate into adverse clinical net-benefit ratios. This review highlights that using certain NOAC regimens proven effective for stroke prevention in AF can reduce the rate of bleeding without increasing ischemic or embolic events. Furthermore, additive ASA in triple anti-thrombotic regimens should be limited to 1 month and individual weighing of ischemic versus bleeding risk during the first 30 days seems to be reasonable.