Résumé
Bien que les anticoagulants oraux directs (AODs) ne permettent pas de suivi biologique au vu de leur pharmacocinétique, le délai d’instauration du traitement après une chirurgie, l’âge, le poids, la fonction hépatique, la fonction rénale et les traitements concomitants sont autant de facteurs faisant varier leur profil de sécurité. Le dabigatran est à éviter chez des patients présentant une insuffisance rénale, et lors de coprescriptions avec des inhibiteurs/inducteurs de la P-gp. Les anti-Xa sont ceux qui présentent le profil de sécurité le plus sûr dans une population âgée, si toutefois les interactions médicamenteuses avec les inhibiteurs/inducteurs du CYP3A4 sont contrôlées. La puissance des anti-Xa réside dans l’inhibition rapide, directe, compétitive, réversible et avec une bonne affinité de l’activité enzymatique du facteur Xa libre ou dans le complexe prothrombinase, empêchant la génération de thrombine. Les tests de la coagulation altérés sont le taux de prothrombine, le TCA (moins sensible) et les tests chromogéniques. Quant au dabigatran, il inhibe directement, de façon réversible, rapide et compétitive, la thrombine libre ou liée. Le temps de thrombine et celui d’écarine sont les deux tests de la coagulation reflétant l’activité du dabigatran. Le dabigatran modifie aussi le TCA mais pas de manière concentration-dépendante. À l’heure actuelle, il n’existe pas d’antidotes commercialisés pour réverser leurs effets, mais certains sont actuellement en cours de développement.
Abstract
Despite DOAs not being able to undergo laboratory monitoring regarding their pharmacokinetics, the delay in starting treatment after surgery, age, weight, liver function, renal function and concomitant treatments are all factors that may alter their safety profile. Dabigatran is to be avoided by patients presenting with renal impairment, and also when co-prescribed with P-gp inhibitors/inducers. Anti-Xas are the medicinal products with the most reliable safety profile for the elderly population, if interactions with medicines such as CYP3A4 inhibitors/inducers are controlled. The power of anti-Xas lies in its quick, direct, competitive and reversible inhibition plus the strong affinity of the Xa factor enzyme activity, whether the Xa factor is free or within the prothrombinase complex, preventing the generation of thrombin. Tests for modified coagulation include the prothrombin ratio, aPTT (less sensitive), and chromogenic tests. With dabigatran, this product directly inhibits free or bound thrombin, reversibly, rapidly and competitively. The thrombin and ecarin clotting times are the two coagulation tests that reflect the activity of dabigatran. Dabigatran also modifies the aPTT, but not in a concentration dependent manner. Currently, there are no commercially available antidotes to reverse the effects of anticoagulants, however, some are in the process of being developed.
Abbreviations
- AODs:
-
Anticoagulant oraux directs
- ASC:
-
Aire sous la courbe
- AVK:
-
Antivitamine K
- BCRP:
-
Breast Cancer Resistance Protein
- Cmax:
-
Concentration maximale
- CYP:
-
Cytochrome P450
- ECT:
-
Ecarin Clotting Time ou temps d’écarine
- HBPM:
-
Héparine de bas poids moléculaire
- IC50:
-
Concentration inhibitrice 50
- IH:
-
Insuffisance hépatique
- INR:
-
International normalized ratio
- IR:
-
Insuffisance rénale
- Ki:
-
Constante d’inhibition
- Koff :
-
Constante de dissociation
- Kon :
-
Constante d’association
- P-gp:
-
P-glycoprotéine
- TCA:
-
Temps de céphaline activé
- Tmax:
-
Temps pour obtenir la concentration plasmatique maximale
- TP:
-
Taux de prothrombine
- TQ:
-
Temps de Quick
- TT:
-
Temps de thrombine
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Ayme-Dietrich, E., Aubertin-Kirch, G. & Monassier, L. Les anticoagulants oraux directs chez le sujet âgé : point de vue du pharmacologue. cah. année gerontol. 7, 88–97 (2015). https://doi.org/10.1007/s12612-015-0457-3
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DOI: https://doi.org/10.1007/s12612-015-0457-3