The correlations between anti-factor Xa activity values and PT/APTT at peak and trough times in patients with venous thromboembolism using high dose of apixaban

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Ono ◽  
K Fukushima ◽  
T Yamazaki ◽  
H Takahashi ◽  
Y Hori
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
High Dose ◽  
Peak Time ◽  
Strong Positive Correlation ◽  
Positive Correlation ◽  
Chromogenic Assay ◽  
Routine Coagulation

Abstract Background The high dose (20mg/day) of apixaban is used for the initial treatment of venous thromboembolism for the first week. Although patients taking direct oral anticoagulants do not require routine coagulation monitoring, the correlations between anti-factor Xa activity (AXA) and routine coagulation markers such as prothrombin time (PT) and activated partial thromboplastin time (APTT) at peak and trough times especially when using high dose of apixaban have not been reported so far. Purpose The purpose is to assess the correlations between AXA values and PT/APTT at peak and trough times in patients with venous thromboembolism using high dose of Apixaban. Methods Twenty-six patients (10 male; 71±15 years) with proximal venous thromboembolism or pulmonary embolism using high dose (20mg/day) of apixaban were enrolled. We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, PT and APTT at peak and trough times. The peak time was defined as 3 hours after the intake of apixaban, and the trough time was defined as that immediately before the intake of apixaban. Results A significant and strong positive correlation was observed between AXA and PT at both peak and trough times (R=0.795, p<0.01 and R=0.766, p<0.01, respectively). A significant and moderate positive correlation was observed between AXA and APTT at trough time (R=0.527, p<0.01), but no correlation was observed between AXA and APTT at peak time (R=0.366, p=0.07). Conclusion Our findings reveal the relationship between AXA and PT at peak and trough times has a significant strong correlation. These results suggest measuring of PT may be alternative and effective way of monitoring of AXA values when using high dose of apixaban. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract 15194: The Distribution of Anti-factor Xa Activity Values, Prothrombin Time and Activated Partial Thromboplastin Time Assessed at Multiple Points in Patients on Edoxaban Therapy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ryohei Ono ◽  
Kenichi Fukushima ◽  
Hidehisa R Takahashi ◽  
Yasuhiko Hori ◽  
Yoshio Kobayashi
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Peak Time ◽  
Multiple Points ◽  
Once Daily ◽  
Chromogenic Assay ◽  
Drug Concentrations ◽  
Prescribing Information ◽  
Routine Coagulation

Introduction: Edoxaban is one of the direct oral anticoagulants (DOACs) used for non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Chromogenic anti-factor Xa activity (AXA) is the appropriate assay to measure the pharmacodynamics of a factor Xa inhibitor and to estimate plasma drug concentrations. Although patients taking DOACs do not require routine coagulation monitoring, the distributions of AXA values have not been assessed at multiple points in the previous study. Purpose: To clarify the distribution of AXA values at two-hour intervals in patients taking edoxaban. Methods: Sixteen patients (66.8 ± 9.6 years, 11 males) with NVAF or VTE on edoxaban therapy were enrolled in the study. We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, at two-hour intervals (from immediately before the intake of edoxaban to 8 hours after the intake). The dosage of edoxaban was 30 mg (n=11) once daily (OD) or 60 mg (n=5) OD according to the prescribing information. Results: The distributions of AXA values of 30 mg OD at 0, 2, 4, 6 and 8 hours after the intake of edoxaban were 0.12±0.08, 0.80±0.48, 0.94±0.48, 0.72±0.34 and 0.53±0.32 (IU/mL), respectively. The distributions of AXA values of 60 mg OD at 0, 2, 4, 6 and 8 hours after the intake of edoxaban were 0.17±0.04, 1.59±0.76, 1.43±0.34, 1.29±0.32 and 0.96±0.21 (IU/mL), respectively. Conclusions: Our findings reveal that the peak time of AXA values might be different depending on the dosage. The peak time of 30 mg OD is between 0 to 4 hours, whereas that of 60 mg OD is between 2 to 6 hours after the intake of edoxaban. In addition, the AXA values of 60 mg OD are almost twice as much as that of 30 mg at each point.

scholarly journals The distribution of anti-factor Xa activity value, PT and APTT at peak and trough times in patients with direct anti-factor Xa inhibitors

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Ono ◽  
K Fukushima ◽  
T Yamazaki ◽  
H Takahashi ◽  
Y Hori
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
International Normalized Ratio ◽  
Activated Partial Thromboplastin Time ◽  
Peak Time ◽  
Chromogenic Assay ◽  
Standard Values ◽  
Prescribing Information ◽  
Routine Coagulation

Abstract Background Although patients taking direct oral anticoagulants (DOACs) do not require routine coagulation monitoring, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), PT-international normalized ratio (INR) and activated partial thromboplastin time (APTT) in patients on apixaban, edoxaban and rivaroxaban therapy is still not clear. Purpose The aim is to set the standard values of AXA values, PT, PT-INR and APTT in patients using DOACs. Methods We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, PT, PT-INR and APTT at trough and peak times in 224 patients with non-valvular atrial fibrillation and venous thromboembolism, of whom 90 received apixaban, 100 received edoxaban and 34 received rivaroxaban. The peak time was defined as 3 hours after the intake of apixaban or rivaroxaban, and 2 hours after the intake of edoxaban. The trough time was defined as that immediately before the intake. The AXA values, PT, PT-INR and APTT were measured at least 72 hours after the start of treatment. The dosage of DOACs is defined according to the prescribing information in Japan. Results (The order of results below is apixaban, edoxaban and rivaroxaban, respectively.) The average AXA values were 2.29, 0.23 and 0.39 (IU/mL) at trough time, and 3.04, 1.01 and 1.70 (IU/mL) at peak time. The average PT values were 17.9, 12.9 and 13.1 (s) at trough time, and 19.7, 15.5 and 17.5 (s) at peak time. The average PT-INR values were 1.49, 1.07 and 1.08 at trough time, and 1.65, 1.29 and 1.45 at peak time. The average APPT values were 34.5, 31.3 and 32.0 (s) at trough time, and 39.5, 35.9 and 39.8 (s) at peak time. Conclusion Our findings reveal the standard values of AXA, PT, PT-INR and APTT in patients using apixaban, edoxaban and rivaroxaban in each dosage. The DOACs should be changed if the measured value is out of those standard values in 90% confidence interval. Funding Acknowledgement Type of funding source: None

scholarly journals Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 985 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Iqbal H. Jaffer ◽  
James C. Fredenburgh
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Prevention Of Recurrence ◽  
Active Cancer ◽  
Routine Coagulation ◽  
Inhibit Factor

The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

scholarly journals Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment

2015 ◽  
Vol 22 (2) ◽  
pp. 144 ◽  
Author(s):  
J.C. Easaw ◽  
M.A. Shea-Budgell ◽  
C.M.J. Wu ◽  
P.M. Czaykowski ◽  
J. Kassis ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Insufficiency ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Patients With Cancer ◽  
Clinical Scenarios ◽  
Increased Risk

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic.PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations.Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti–factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

scholarly journals Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Tania Ahuja ◽  
Kelly Sessa ◽  
Cristian Merchan ◽  
John Papadopoulos ◽  
David Green
Keyword(s):  
Chronic Kidney Disease ◽  
Venous Thromboembolism ◽  
Kidney Disease ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Advanced Chronic Kidney Disease ◽  
Ckd Stage

Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm ( p = 0.498 ). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.

scholarly journals Direct oral anticoagulants and venous thromboembolism

2016 ◽  
Vol 25 (141) ◽  
pp. 295-302 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Direct Anticoagulants ◽  
Deep Vein

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 87-95 ◽  
Author(s):  
Giovanna Elmi ◽  
Giuseppe Di Pasquale ◽  
Raffaele Pesavento
Keyword(s):  
Venous Thromboembolism ◽  
Safety Profile ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Recurrence ◽  
Extended Treatment

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

scholarly journals Clinical pearls: Laboratory assessments of direct oral anticoagulants (DOACS)

2017 ◽  
Vol 37 (04) ◽  
pp. 295-301 ◽  
Author(s):  
Jonathan Douxfils ◽  
Dorothy Adcock ◽  
Robert Gosselin
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Stroke Prevention ◽  
Clinical Laboratory ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Testing ◽  
Testing Plan

SummaryDirect oral anticoagulants (DOACS) are being used for stroke prevention in patients with atrial fibrillation as well as for prophylaxis and treatment of venous thromboembolism. Clinicians who treat, or may encounter, patients with DOAC exposure, should be aware of the limitations of coagulation testing in this setting, and seek counsel from their laboratory to understand the effects of DOACS on coagulation results. Generally, assays that employ clot based principles, or methods that require thrombin or Factor Xa activation or substrates may be affected by the presence of DOACS. The clinical laboratory should have an algorithmic testing plan for adequately assessing the presence of all DOACS and readily provide this information to clinicians. We describe Clinical Pearls for DOAC assessment using common and esoteric coagulation testing.

scholarly journals Clinical pearls: Laboratory assessments of direct oral anticoagulants (DOACS)

Phlebologie ◽  
2018 ◽  
Vol 47 (04) ◽  
pp. 215-221
Author(s):  
Robert Gosselin ◽  
Jonathan Douxfils ◽  
Dorothy Adcock
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Stroke Prevention ◽  
Clinical Laboratory ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Testing ◽  
Testing Plan

SummaryDirect oral anticoagulants (DOACS) are used for stroke prevention in patients with atrial fibrillation as well as for prophylaxis and treatment of venous thromboembolism.Clinicians who treat, or may encounter, patients with DOAC exposure, should be aware of the limitations of coagulation testing in this setting, and seek counsel from their laboratory to understand the effects of DOACS on coagulation results. Generally, assays that employ clot based principles, or methods that require thrombin or Factor Xa activation or substrates may be affected by the presence of DOACS. The clinical laboratory should have an algorithmic testing plan for adequately assessing the presence of all DOACS and readily provide this information to clinicians. We describe Clinical Pearls for DOAC assessment using common and esoteric coagulation testing.

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