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

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.

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

scholarly journals Slightly elevated international normalized ratio predicts bleeding episodes in patients treated with direct oral anticoagulants

2020 ◽  
Vol 48 (6) ◽  
pp. 030006051989443
Author(s):  
Priya Bhardwaj ◽  
Louise Breum Petersen ◽  
Tomas Sorm Binko ◽  
Jan Roland Petersen ◽  
Gitte Gleerup Fornitz
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Direct Factor ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Direct Factor Xa Inhibitors ◽  
Bleeding Episodes

Introduction Patients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs. Methods This retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes. Results INR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively. Conclusions Our results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.

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.

scholarly journals Heparin is more effective than apixaban in inhibiting in vitro contact activated coagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Engelen ◽  
C Van Laer ◽  
M Jacquemin ◽  
C Vandenbriele ◽  
K Peerlinck ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Mechanical Heart Valves ◽  
Contact Activation

Abstract Introduction Contact of blood with artificial surfaces such as mechanical support devices, catheters, and mechanical heart valves activates the contact activation (CA) pathway of coagulation. Furthermore, recent animal data and clinical studies suggest a more important contribution of CA in pathological thrombus formation in other cardiovascular diseases. Direct oral anticoagulants (DOACs) are recommended as first-line treatment in most patients who require long-term anticoagulation. However, because DOACs directly inhibit a single downstream coagulation factor (thrombin (fXIIa) or factor Xa (fXa)), it has been suggested that their efficacy could be reduced in the presence of strong activation of the CA pathway as compared to anticoagulants that target multiple, more upstream located coagulation factors. Purpose To compare the efficacy of a DOAC (apixaban) and heparin to suppress thrombin generation in the presence of strong CA pathway activation. Methods Pooled platelet-poor plasma was spiked with either apixaban (dissolved in DMSO and PBS) or unfractionated heparin to achieve therapeutic plasma levels. SynthASil, a commercially available mixture of phospholipids and silica, was used to stimulate the CA pathway in two different dilutions (1–80 and 5–80). Downstream coagulation was accessed by Thrombin Generation Test using Thrombinoscope by Stago and associated Thrombin Calibrator (activity 640 nM). The endogenous thrombin potential (area under the thrombin generation curve; ETP), peak thrombin generation (PTG), time to peak (ttPeak) and time to start (ttStart) were accessed. Results With decreasing concentrations of apixaban, stimulation with the lower dose SynthASil reveals an increasing ETP and PTG. As expected, ttPeak and ttStart decreased. Even supratherapeutic levels of apixaban (i.e. 1120 ng/mL) could not inhibit thrombin from being generated, in striking contrast with UFH where no thrombin was formed. Using a five times higher dose of SynthASil showed comparable ETP for all concentrations of apixaban, allocated around the control value. PTG, however, slightly increased with decreasing concentrations of apixaban. ttPeak and ttStart slightly decreased. Except for the subtherapeutic UFH concentration of 0,114 IU/mL, no thrombin was generated with UFH. Conclusion UFH is more effective in inhibiting downstream thrombin generation compared to apixaban as a response to activation of the CA pathway in vitro. These findings could help explain why direct inhibitors were not able to show non-inferiority in patients with mechanical heart valves and support the development of specific CA pathway inhibitors for patients with conditions that activate the CA pathway. Thrombin generation curves Funding Acknowledgement Type of funding source: None

Influence of Direct Oral Anticoagulants on Anti–Factor Xa Measurements Utilized for Monitoring Heparin

2017 ◽  
Vol 52 (2) ◽  
pp. 154-159 ◽  
Author(s):  
Kelly A. Macedo ◽  
Peter Tatarian ◽  
Kenneth R. Eugenio
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients

2018 ◽  
Vol 35 (9) ◽  
pp. 903-908 ◽  
Author(s):  
Teresa A. Allison ◽  
Pei Jen Lin ◽  
Jennifer A. Gass ◽  
Kenneth Chong ◽  
Samuel J. Prater ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Prothrombin Complex Concentrate ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Final Analysis ◽  
Factor Xa Inhibitor ◽  
Direct Factor

Objective: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. Methods: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. Results: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. Conclusions: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.

scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

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