Non-vitamin-K oral anticoagulants and laboratory testing: now and in the future

Salmonson, Tomas; Dogné, Jean‐Michel; Janssen, Heidi; Burgos, Juan Garcia; Blake, Paul

doi:10.1093/ehjcvp/pvw032

Cited by 51 publications

(27 citation statements)

References 9 publications

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“…Treatment with DOACs does not require hemostaseologic monitoring by routine. However, chromogenic factor Xa assays with substance specific calibration correlate reliably with the antithrombotic activity and allow the measurement of a functional factor Xa inhibitor plasma level in case of an emergency [23][24][25]. The test was included into the standard of care for patients with acute ischemic stroke at our department, thereby supporting the decisions of recanalization therapies including intravenous thrombolysis [26].…”

Section: Discussionmentioning

confidence: 99%

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

et al. 2020

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Background Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common. Methods Data from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as "appropriate", "underdosed" and "overdosed" in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated. Results 254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHA 2 DS 2-Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0-121.6) vs. 129.2 ng/ml (65.5-207.2); p < 0.001], was associated with higher NIHSS scores on admission [median 5 (IQR 1-10) vs. 3 (1-7); p = 0.041] and worse functional outcome after 3 months (favorable outcome 26.9% vs. 46.9%; p = 0.025). Conclusion One in three patients with ischemic stroke during treatment with oral Xa inhibitors used inappropriate dose regimens. Underdosing was associated with lower functional plasma levels, higher clinical stroke severity and worse functional outcome.

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Section: Discussionmentioning

confidence: 99%

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

et al. 2020

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“…Dabigatran, edaxoban, rivaroxaban, and apixaban are p-glycoprotein substrate. These P-gps are present on the surface of the intestine, bile duct, and renal tubules, which play an efficient role in the transportation of xenobiotic outside the body [3,14]. Rivaroxaban reaches peak plasma concentration in 2-4 hours while the half-life of the drug is 15 hours.…”

Section: Figure 1: Mechanism Of Actionmentioning

confidence: 99%

“…Edoxaban has a peak plasma concentration of about 1 hour and halflife is 11 hours. Renal excretion is about 39% [3][4][15][16].…”

Section: Figure 1: Mechanism Of Actionmentioning

confidence: 99%

“…The difference between VKA and NOACs is that VKA works by reducing the hepatic synthesis of various clotting factors while NOACs work by acting on specific factors of the coagulation cascade [3]. Besides, NOACs do not require routine monitoring, while VKAs have a narrow therapeutic index, which can be very troublesome and costly for patients as well as healthcare providers.…”

Section: Introductionmentioning

confidence: 99%

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Use of New Oral Anticoagulants/ Direct Oral Anticoagulants in Malignant Patients

Khan¹,

Zaidi²,

Razak³

et al. 2020

Cureus

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Vitamin K antagonists are being used in the last five decades as an effective anticoagulant. However, for the past few years, new oral anticoagulants (NOACs) have been introduced as newer anticoagulant agents, which are gradually replacing the previously used vitamin K antagonist. Yet, these agents have not fully replaced the use of warfarin and heparin. NOACs have few advantages over the vitamin K antagonist as they act on a specific factor of coagulation cascade rather than inhibiting the whole vitamin K synthesis. In this article, all the data has been searched electronically on PubMed and PRISMA guidelines were not followed. Instead, we used MOOSE statements and the data searched on PubMed was from articles published in the last five years. A total of 12,269 patients were observed;,out of which 64.19% had active cancer and 35.80% was observed as a control group comprised of both male or female participants. Approximately 61.14% were using NOACs, 42.83% were on warfarin, and 2.72% were on low-molecular-weight heparin (LMWH). The NOACs used in different patients were in the following percentages; edoxaban (6.81%), apixaban (5.28%), dabigatran (10.09%), and rivaroxaban (10.02%). The use of NOACs has been increasing day by day but these agents have not completely replaced the warfarin or heparin, because of some demerits associated with the use of warfarin and some conditions where these drugs should be avoided. All NOACs have either hepatic or renal clearance so the hepatic activity and creatinine clearance rate must be monitored before the start of NOACs. The drug interaction between anticancer drugs and NOACs is still not fully reported. The effects of NOACs in AF and VTE are therapeutically effective, but in oncology patients several other co-factors are also involved with the use of NOACs due to which, it is either contraindicated or in some cases dose adjustment is required. However, very little information has been collected and more investigation must be done in this perspective. Categories: Cardiology, Oncology, Hematology Keywords: new oral anti-coagulants, atrial fibrillation in cancer patients, venousthromboembolisim in cancer patients, cancer assossiated thrombosis, rivaroxiban in cancer patients, apixaban in cancer patients, edoxaban in cancer patients, dabigatrin in cancer patients Open Access Review Article

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“…However, the current clinical data are not sufficient for the recognition of a better or safer anticoagulant among DOACs. Standard laboratory clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (APTT), diluted thrombin time (dTT) or ecarin clotting assay (ECA), have already been examined in patients taking DOACs, showing conflicting data regarding the mechanism of action of DOACs . For example, PT and APTT assays possess different sensitivities for rivaroxaban than for apixaban.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients

Džudović

Subota

et al. 2018

J Clin Pharm Ther

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Summary What is known and Objective Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients. Methods After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D‐dimer and fibrinogen, were measured, and the values were compared between the groups. Results and Discussion One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0‐4.0) vs 2.1 (1.5‐2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D‐dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups. What is new and Conclusion Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption.

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Non-vitamin-K oral anticoagulants and laboratory testing: now and in the future

Cited by 51 publications

References 9 publications

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

Use of New Oral Anticoagulants/ Direct Oral Anticoagulants in Malignant Patients

Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients

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