Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants

2021 ◽  
Author(s):  
Michael Hardy ◽  
Claudia Dellanoce ◽  
Jonathan Douxfils ◽  
Audrey Carlo ◽  
Sarah Lessire ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants

scholarly journals Plasma levels do not predict thrombin generation in patients taking direct oral anticoagulants

2021 ◽  
Author(s):  
Michael Metze ◽  
Tristan Klöter ◽  
Stephan Stöbe ◽  
Björn Rechenberger ◽  
Roland Siegemund ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants

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

scholarly journals Rivaroxaban dose adjustment using thrombin generation in severe congenital protein C deficiency and warfarin-induced skin necrosis

2018 ◽  
Vol 2 (2) ◽  
pp. 142-145 ◽  
Author(s):  
Neethu Menon ◽  
Ravi Sarode ◽  
Ayesha Zia
Keyword(s):  
Skin Necrosis ◽  
Protein C ◽  
Dose Adjustment ◽  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Protein C Deficiency ◽  
Thrombin Generation Assay ◽  
Key Points ◽  
Congenital Protein C Deficiency

Key Points Rivaroxaban was efficacious and safe in a child with protein C deficiency to prevent the recurrence of skin necrosis or venous thrombosis. The dosage of direct oral anticoagulants in children with thrombophilia is unclear; a thrombin generation assay may be useful to adjust it.

scholarly journals Laboratory Assessment of the Anticoagulant Activity of Apixaban in Patients With Nonvalvular Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 194S-201S ◽  
Author(s):  
Elias Kyriakou ◽  
Konstantinos Katogiannis ◽  
Ignatios Ikonomidis ◽  
George Giallouros ◽  
Georgios K. Nikolopoulos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Nonvalvular Atrial Fibrillation ◽  
Laboratory Assessment ◽  
Thrombin Generation Assay ◽  
Significant Difference

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

scholarly journals Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants

2020 ◽  
Vol 4 (4) ◽  
pp. 610-618
Author(s):  
Michael Metze ◽  
Christian Pfrepper ◽  
Tristan Klöter ◽  
Stephan Stöbe ◽  
Roland Siegemund ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Inhibition Of Thrombin

scholarly journals Influence of direct oral anticoagulants on thrombin generation on Ceveron TGA

2021 ◽  
Author(s):  
Christian Pfrepper ◽  
Lisa‐Charlott Behrendt ◽  
Hagen Bönigk ◽  
Thomas Siegemund ◽  
Michael Metze ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants

scholarly journals Automated Thrombin Generation Assay for Rivaroxaban, Apixaban, and Edoxaban Measurements

2021 ◽  
Vol 8 ◽  
Author(s):  
Tamana Meihandoest ◽  
Jan-Dirk Studt ◽  
Adriana Mendez ◽  
Lorenzo Alberio ◽  
Pierre Fontana ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Strong Association ◽  
Area Under The Curve ◽  
Lag Time ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Thrombin Generation Assay ◽  
Drug Concentrations

Background: The thrombin generation assay (TG) is a promising approach to measure the degree of anticoagulation in patients treated with direct oral anticoagulants (DOAC). A strong association with plasma drug concentrations would be a meaningful argument for the potential use to monitor DOAC.Objectives: We aimed to study the correlation of TG with rivaroxaban, apixaban, and edoxaban drug concentrations in a large, prospective multicenter cross-sectional study.Methods: Five-hundred and fifty-nine patients were included in nine tertiary hospitals. The Technothrombin® TG was conducted in addition to an anti-Xa assay; LC-MS/MS was performed as the reference standard.Results: Correlation (rs) between thrombin generation measurements and drug concentrations was −0.72 for peak thrombin generation (95% confidence interval, CI, −0.77, −0.66), −0.55 for area under the curve (AUC; 95% CI −0.61, −0.48), and 0.80 for lag time (95% CI 0.75, 0.84). In contrast, rs was 0.96 with results of the anti-Xa activity (95% CI 0.95–0.97). Sensitivity with regard to the clinically relevant cut-off value of 50 μgL−1 was 49% in case of peak thrombin generation (95% CI, 44, 55), 29% in case of AUC (95% CI, 24, 34), and 64% in case of lag time (95% CI, 58, 69). Sensitivity of the anti-Xa assay was 95% (95% CI, 92, 97).Conclusions: The correlation of thrombin generation measurements with DOAC drug concentrations was weak, and clinically relevant drug levels were not predicted correctly. Our results do not support an application of TG in the monitoring of DOAC.

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