Tags

Type your tag names separated by a space and hit enter

Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed.
Blood Coagul Fibrinolysis. 2018 Mar; 29(2):148-154.BC

Abstract

: Direct oral anticoagulants (DOACs) are increasingly being used, primarily due to their drug stability and patient convenience. Although these drugs have been evaluated to be well tolerated in numerous clinical trials, their impact on in-vivo anticoagulation effect, variability and therapeutic drug level remains unknown. Hence, we aim to study the effect and variability of DOACs on thrombin generation via the calibrated automated thrombogram. Anonymized coagulation specimens from outpatients on warfarin were collected. Pooled normal plasma samples were spiked with increasing concentrations of dabigatran, rivaroxaban and apixaban. Similarly, plasma samples with normal coagulation profiles were spiked with two concentrations each of dabigatran, rivaroxaban and apixaban. Thrombin generation via calibrated automated thrombogram was run using the above samples and compared with a dataset of normal controls. Increasing international normalized ratio was associated with a reduction of endogenous thrombin potential (ETP) and thrombin peak and increasing lag time. Factor Xa inhibitors produced a flattened thrombin generation curve with a reduction of thrombin peak and relative preservation of ETP. Direct thrombin inhibitors produced a reduction of both ETP and thrombin peak and increasing lag time. Seventy-one citrated plasma samples (26 dabigatran, 21 rivaroxaban and 24 apixaban) were evaluated. The two concentrations produced a reduction of thrombin generation parameters with significant interindividual variability compared with neat plasma of 35-93, 13-31 and 18-71% and for dabigatran, rivaroxaban and apixaban, respectively. Thrombin generation can measure the anticoagulation effect of commonly used DOACs, with each drug having a unique thrombin generation profile. The variability noted using the same concentration suggests significant interindividual pharmacodynamic differences, which maybe relevant with respect to efficacy as well as bleeding side effects. Further delineation of the modifiers of interindividual differences is required in the in-vivo setting.

Authors+Show Affiliations

Austin Pathology, Austin Health, Heidelberg.Department of Clinical Haematology, Northern Health, Epping.Australian Centre for Blood Disease, Monash University, Melbourne, Victoria, Australia.Department of Clinical Haematology, Northern Health, Epping. Florey Institute of Neuroscience and Mental Health, Parkville. Australian Centre for Blood Disease, Monash University, Melbourne, Victoria, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29176379

Citation

Rigano, Joseph, et al. "Thrombin Generation Estimates the Anticoagulation Effect of Direct Oral Anticoagulants With Significant Interindividual Variability Observed." Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis, vol. 29, no. 2, 2018, pp. 148-154.
Rigano J, Ng C, Nandurkar H, et al. Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed. Blood Coagul Fibrinolysis. 2018;29(2):148-154.
Rigano, J., Ng, C., Nandurkar, H., & Ho, P. (2018). Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed. Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis, 29(2), 148-154. https://doi.org/10.1097/MBC.0000000000000678
Rigano J, et al. Thrombin Generation Estimates the Anticoagulation Effect of Direct Oral Anticoagulants With Significant Interindividual Variability Observed. Blood Coagul Fibrinolysis. 2018;29(2):148-154. PubMed PMID: 29176379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed. AU - Rigano,Joseph, AU - Ng,Cheryl, AU - Nandurkar,Harshal, AU - Ho,Prahlad, PY - 2017/11/28/pubmed PY - 2018/8/11/medline PY - 2017/11/28/entrez SP - 148 EP - 154 JF - Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis JO - Blood Coagul. Fibrinolysis VL - 29 IS - 2 N2 - : Direct oral anticoagulants (DOACs) are increasingly being used, primarily due to their drug stability and patient convenience. Although these drugs have been evaluated to be well tolerated in numerous clinical trials, their impact on in-vivo anticoagulation effect, variability and therapeutic drug level remains unknown. Hence, we aim to study the effect and variability of DOACs on thrombin generation via the calibrated automated thrombogram. Anonymized coagulation specimens from outpatients on warfarin were collected. Pooled normal plasma samples were spiked with increasing concentrations of dabigatran, rivaroxaban and apixaban. Similarly, plasma samples with normal coagulation profiles were spiked with two concentrations each of dabigatran, rivaroxaban and apixaban. Thrombin generation via calibrated automated thrombogram was run using the above samples and compared with a dataset of normal controls. Increasing international normalized ratio was associated with a reduction of endogenous thrombin potential (ETP) and thrombin peak and increasing lag time. Factor Xa inhibitors produced a flattened thrombin generation curve with a reduction of thrombin peak and relative preservation of ETP. Direct thrombin inhibitors produced a reduction of both ETP and thrombin peak and increasing lag time. Seventy-one citrated plasma samples (26 dabigatran, 21 rivaroxaban and 24 apixaban) were evaluated. The two concentrations produced a reduction of thrombin generation parameters with significant interindividual variability compared with neat plasma of 35-93, 13-31 and 18-71% and for dabigatran, rivaroxaban and apixaban, respectively. Thrombin generation can measure the anticoagulation effect of commonly used DOACs, with each drug having a unique thrombin generation profile. The variability noted using the same concentration suggests significant interindividual pharmacodynamic differences, which maybe relevant with respect to efficacy as well as bleeding side effects. Further delineation of the modifiers of interindividual differences is required in the in-vivo setting. SN - 1473-5733 UR - https://www.unboundmedicine.com/medline/citation/29176379/Thrombin_generation_estimates_the_anticoagulation_effect_of_direct_oral_anticoagulants_with_significant_interindividual_variability_observed_ L2 - http://dx.doi.org/10.1097/MBC.0000000000000678 DB - PRIME DP - Unbound Medicine ER -