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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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Non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with atrial fibrillation.
Undas, A, Drabik, L
Anatolian journal of cardiology. 2020;(1):10-18
Abstract
Non-vitamin K antagonist oral anticoagulants (NOACs), or direct oral anticoagulants have not been tested in randomized trials conducted in patients with atrial fibrillation (AF), who had malignant disease. However, their use in cancer patients increases and real-life evidence for their effectiveness and safety in this vulnerable subset of patients is growing. The challenges of the use of NOACs in cancer patients with AF and the current expert opinions on this subject have been summarized in this review article.
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The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence.
Chin, KY
Nutrients. 2020;(5)
Abstract
Vitamin K is a cofactor of γ-glutamyl carboxylase, which plays an important role in the activation of γ-carboxyglutamate (gla)-containing proteins that negatively regulate calcification. Thus, vitamin K status might be associated with osteoarthritis (OA), in which cartilage calcification plays a role in the pathogenesis of the disease. This review collates the evidence on the relationship between vitamin K status (circulating or dietary intake level of vitamin K, or circulating uncarboxylated gla proteins) and OA from human observational studies and clinical trial, to examine its potential as an agent in preventing OA. The current literature generally agrees that a sufficient level of vitamin K is associated with a lower risk of OA and pathological joint features. However, evidence from clinical trials is limited. Mechanistic study shows that vitamin K activates matrix gla proteins that inhibit bone morphogenetic protein-mediated cartilage calcification. Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation. Although the current data are insufficient to establish the optimal dose of vitamin K to prevent OA, ensuring sufficient dietary intake seems to protect the elderly from OA.
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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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Current Therapy in CKD Patients Can Affect Vitamin K Status.
Cozzolino, M, Cianciolo, G, Podestà, MA, Ciceri, P, Galassi, A, Gasperoni, L, Manna, G
Nutrients. 2020;(6)
Abstract
Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.
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Venous Thromboembolism in Children: From Diagnosis to Management.
Lassandro, G, Palmieri, VV, Palladino, V, Amoruso, A, Faienza, MF, Giordano, P
International journal of environmental research and public health. 2020;(14)
Abstract
Venous thromboembolism (VTE) in children is a rare occurrence, although in recent decades we have seen an increase due to several factors, such as the rise in survival of subjects with chronic conditions, the use of catheters, and the increased sensitivity of diagnostic tools. Besides inherited thrombophilia, acquired conditions such as cardiovascular diseases, infections, chronic disorders, obesity and malignancy are also common risk factors for paediatric VTE. The treatment of paediatric VTE consists of the use of heparins and/or vitamin K antagonists to prevent dissemination, embolization, and secondary VTE. Randomized clinical trials of direct oral anticoagulants in paediatric VTE are ongoing, with the aim to improve the compliance and the care of patients. We reviewed the physiological and pathological mechanisms underlying paediatric thrombosis and updated the current diagnosis and treatment options.
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Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage.
Dai, L, Schurgers, LJ, Shiels, PG, Stenvinkel, P
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(Suppl 2):ii31-ii37
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Abstract
Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage-induced cellular senescence and 'inflammaging' may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2-related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.
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Vitamin K effects in human health: new insights beyond bone and cardiovascular health.
Fusaro, M, Gallieni, M, Porta, C, Nickolas, TL, Khairallah, P
Journal of nephrology. 2020;(2):239-249
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Abstract
Vitamin K is a cofactor for the function of the enzyme γ-glutamyl carboxylase, necessary for the activation of multiple vitamin K dependent-proteins. Vitamin K dependent-proteins (VKDPs) have important roles in bone health, vascular health, metabolism, reproduction as well as in cancer progression. Vitamin K deficiency is common in different conditions, including kidney disease, and it may influence the activity of VKDPs. This review discusses vitamin K status in human health and the physiologic and pathologic roles of VKDPs, beyond the established effects in skeletal and cardiovascular health.
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Real-world use of nonvitamin K antagonist oral anticoagulant in atrial fibrillation patients with liver disease: A meta-analysis.
Dai, Q, Deng, X, Zhou, L, Zhang, L, Xiao, X, Liao, Y
Clinical cardiology. 2020;(7):676-683
Abstract
Several studies have investigated the effectiveness and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and liver disease. Herein, we conducted a meta-analysis to compare the effect of NOACs with VKAs in patients with AF and liver disease. We also conducted a subsidiary analysis to compare the risk of liver injury between NOACs and VKA in AF patients. We systematically searched the PubMed and Embase databases from January 2009 to May 2020 for the relevant studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were selected and pooled using a random-effects model. A total of six cohorts were included. Compared with VKA use, the use of NOACs was associated with reduced risks of stroke or systemic embolism (HR 0.68, 95% CI 0.49-0.93), all-cause death (HR 0.69, 95% CI 0.63-0.75), and intracranial bleeding (HR 0.49, 95% CI 0.40-0.59), whereas the outcomes of major bleeding (HR 0.72, 95% CI 0.51-1.01) and gastrointestinal bleeding (HR 0.84, 95% CI 0.51-1.36) were not significantly different between groups in AF patients with liver disease. Moreover, compared with VKA use, the use of NOACs was associated with a reduced risk of liver injury (HR 0.72, 95% CI 0.61-0.84) in AF patients. Compared with VKAs, the use of NOACs was associated with reduced risks of stroke or systemic embolism, all-cause death, and intracranial bleeding in AF patients with liver disease, and associated with a reduced risk of liver injury in AF patients.