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1.
Effect of Therapeutically Related Drugs on Coagulation-Anticoagulation Balance in Acute Promyelocytic Leukemia.
Xiao, M, Zhou, P, Sun, K
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2022;:10760296221080166
Abstract
Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can reduce the risk of bleeding, but the potential for thrombosis needs to be addressed in some cases. The role of arsenic agent in correcting coagulation disorder remains to be studied, but oral arsenic agent shows potential advantages in coagulation recovery compared with intravenous agent, and chemotherapy can aggravate the progress of coagulation disease. In addition to early application of ATRA, avoiding invasive procedures and transfusion support can reduce the risk of bleeding. Whether the administration of heparin, thrombomodulin, recombinant factor VIIa or antifibrinolytics reduces the risk of bleeding and thrombosis associated with APL remains to be further explored, and their routine use outside of clinical trials is not recommended. This article reviews the effects of related drugs on coagulation-anticoagulation balance in APL patients.
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2.
Antithrombotic strategies in elderly patients with acute coronary syndrome.
Dillinger, JG, Laine, M, Bouajila, S, Paganelli, F, Henry, P, Bonello, L
Archives of cardiovascular diseases. 2021;(3):232-245
Abstract
Elderly patients represent a growing proportion of the acute coronary syndrome population in Western countries. However, their frequent atypical symptoms at presentation often lead to delays in management and to misdiagnosis. Furthermore, their prognosis is poorer than that of younger patients because of physiological changes in platelet function, haemostasis and fibrinolysis, but also a higher proportion of comorbidities and frailty, both of which increase the risk of recurrent thrombotic and bleeding events. This complex situation, with ischaemic and haemorrhagic risk factors often being intertwined, may lead to confusion about the required treatment strategy, sometimes resulting in inadequate management or even to therapeutic nihilism. It is therefore critical to provide a comprehensive overview of our understanding of the pathophysiological processes underlying acute coronary syndrome in elderly patients, and to summarise the results from the latest clinical trials to help decision making for these high-risk patients.
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3.
Female Sex as a Thromboembolic Risk Factor in the Era of Nonvitamin K Antagonist Oral Anticoagulants.
Gallù, M, Marrone, G, Legramante, JM, De Lorenzo, A, Di Daniele, N, Noce, A
Cardiovascular therapeutics. 2020;:1743927
Abstract
Sex-specific differences have been definitively demonstrated in cardiovascular (CV) diseases. These differences can also impact on the effects of CV therapies. Female sex is recognized as an independent predictor of thromboembolic risk, particularly in older patients. Most of strokes are due to atrial fibrillation (AF). Women affected by AF have higher stroke risk compared to men. The introduction of novel oral anticoagulants (NOACs) for long-term anticoagulation completely changed the anticoagulant therapeutic approach and follow-up of patients affected by nonvalvular atrial fibrillation (NVAF). CHA2DS2-VASc stroke risk scoring in use in the current international guidelines attributes 1 point to "female sex". Besides, no anticoagulation is indicated for AF female patients without other risk factors. Interestingly, NOACs seem to normalize the differences between males and females both in terms of safety and efficacy, whereas residual higher stroke risk and systemic embolism persist in AF women treated with vitamin K antagonist anticoagulants VKA with optimal time in therapeutic range. Based on the CHA2DS2-VASc score, NOACs represent the preferred choice in NVAF patients. Moreover, complete evaluation of apparently lower risk factor along with concomitant clinical conditions in AF patients appears mandatory, particularly for female patients, in order to achieve the most appropriate anticoagulant treatment, either in male or in female patients. The present review was performed to review sex differences in AF-related thromboembolic risk reported in the literature and possibly highlight current knowledge gaps in prevention and management that need further research.
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4.
A review of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery.
Milling, TJ, Ziebell, CM
Trends in cardiovascular medicine. 2020;(2):86-90
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Abstract
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.
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Emerging clinical setting of direct oral anticoagulants: atherothrombotic events prevention.
Di Fusco, SA, Lucà, F, Gulizia, MM, Gabrielli, D, Colivicchi, F
Journal of cardiovascular medicine (Hagerstown, Md.). 2020;(1):1-5
Abstract
: Despite substantial progress in the treatment of atherosclerotic disease a non-negligible rate of acute atherothrombotic events persists. Evidence suggesting a safer profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists and the involvement of coagulation in the atherosclerotic process has led to exploration of the role of DOACs in the prevention of atherothrombotic events. In this review, we discuss the findings of recent studies on DOACs, particularly rivaroxaban, in atherothrombotic disease which represents a new clinical setting for oral anticoagulants.
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6.
Coagulopathy reversal in intracerebral haemorrhage.
Sweidan, AJ, Singh, NK, Conovaloff, JL, Bower, M, Groysman, LI, Shafie, M, Yu, W
Stroke and vascular neurology. 2020;(1):29-33
Abstract
As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.
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7.
The rebirth of the contact pathway: a new therapeutic target.
Srivastava, P, Gailani, D
Current opinion in hematology. 2020;(5):311-319
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Abstract
PURPOSE OF REVIEW Anticoagulation with vitamin-K antagonists or direct oral anticoagulants is associated with a significant risk of bleeding. There is a major effort underway to develop antithrombotic drugs that have a smaller impact on hemostasis. The plasma contact proteins factor XI (FXI) and factor XII (FXII) have drawn considerable interest because they contribute to thrombosis but have limited roles in hemostasis. Here, we discuss results of preclinical and clinical trials supporting the hypothesis that the contact system contributes to thromboembolic disease. RECENT FINDINGS Numerous compounds targeting FXI or FXII have shown antithrombotic properties in preclinical studies. In phase 2 studies, drugs-targeting FXI or its protease form FXIa compared favorably with standard care for venous thrombosis prophylaxis in patients undergoing knee replacement. While less work has been done with FXII inhibitors, they may be particularly useful for limiting thrombosis in situations where blood comes into contact with artificial surfaces of medical devices. SUMMARY Inhibitors of contact activation, and particularly of FXI, are showing promise for prevention of thromboembolic disease. Larger studies are required to establish their efficacy, and to establish that they are safer than current therapy from a bleeding standpoint.
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Rivaroxaban for prevention and treatment of venous thromboembolism.
Chan, NC, Weitz, JI
Future cardiology. 2019;(2):63-77
Abstract
Until recently, heparins and vitamin K antagonists (VKAs) were the cornerstones for prevention and treatment of venous thromboembolism (VTE). This situation changed with the introduction of the direct oral anticoagulants, which are now replacing low-molecular-weight heparin for thromboprophylaxis after elective hip or knee arthroplasty and VKAs for VTE treatment. Rivaroxaban, an oral factor Xa inhibitor, was the first direct oral anticoagulant licensed for VTE prevention and treatment. This paper provides the rationale for factor Xa as a target for anticoagulants, describes the development of rivaroxaban, reviews its pharmacological profile, discusses the clinical trials with rivaroxaban for VTE prevention and treatment and highlights areas of uncertainty.
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[Modern treatment of deep vein thrombosis and pulmonary embolism].
Renczes, J, Lindhoff-Last, E
Der Internist. 2019;(6):644-655
Abstract
Virchow's triad has been known for a 100 years. The development of therapeutic possibilities during this time was enormous. Today anticoagulant therapy is much more differentiated. Four new oral substances have replaced the traditional treatment with vitamin K antagonists in angiology. A standardized dosage is available. The monitoring of the coagulation parameters is no longer necessary, but it is important to monitor renal function. Direct oral anticoagulants are approved for the treatment of venous thrombosis and pulmonary embolism, but not during pregnancy or in children. Severe bleeding complications, especially intracerebral bleeding, are less common. The incidence of venous thromboembolism is still high. Obesity and cancer are of particular importance. The "therapeutic pact" with the patient requires that physicians master the art of "talking medicine".
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10.
The efficacy and safety of direct oral anticoagulants in patients with chronic renal insufficiency: A review of the literature.
Weber, J, Olyaei, A, Shatzel, J
European journal of haematology. 2019;(4):312-318
Abstract
Direct oral anticoagulants (DOACs) have been shown to be superior to vitamin K antagonists (VKAs) in regards to safety and efficacy in numerous clinical trials and are now the preferred oral anticoagulant by multiple professional societies. However, patients with significant levels of organ dysfunction were excluded from all major clinical trials, leaving the clinical benefit in these subsets uncertain. Patients with chronic kidney disease (CKD) specifically often require anticoagulation for acute or long-term indications such as venous thromboembolism, atrial fibrillation, or mechanical heart valves. The efficacy and safety of anticoagulation in patients with renal failure is less certain, however, particularly with DOACs which have altered pharmacokinetics in patients with renal failure and limited observational data on their use in this population. In this review, we compile the most up to date data on the DOAC use in patients with CKD. DOAC use in patients with ESRD and advanced CKD is increasing despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin. Apixaban has the greatest amount of outcomes research supporting its use over warfarin in this patient population; however, further research on DOAC safety and efficacy in those with advanced CKD is still needed.