Direct oral anticoagulants (DOACs): From the laboratory point of view

Abstract

Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring. Despite these advantages, there are clinical conditions in which laboratory measurement of DOACs should be performed. Although DOACs have an impact on screening haemostasis assays (prothrombin time, PT; activated partial thromboplastin time, aPTT; and thrombin time, TT), these tests are not appropriate for quantifying drug levels. Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.

Dabigatran-related Nephropathy Complicated by Tubulointerstitial Nephritis in a Patient with a Normal Renal Function and Undiagnosed IgA Nephropathy

“…A substantially reduced number of nephrons results in hyperperfusion of the surviving glomeruli and glomerular hypertension, rendering them vulnerable to glomerular hemorrhaging ( 9 ). Although many reports on dabigatran-related nephropathy have been published, dabigatran is an oral direct thrombin inhibitor that reduces thrombin activation ( 18 ). Therefore, activation of protease activated receptor 1 (PAR-1), the main agonist of thrombin signaling, was shown to be reduced.…”

Inhospital outcomes of myocardial infarction in patients receiving direct oral anticoagulants

“…ПОАК блокируют синтез или функцию факторов свертывания крови, таких как тромбин, факторы II, VII, IX, X и XI, что способствует замедлению скорости образования сгустка [10]. Воздействуя на звенья коагуляционного каскада, ПОАК приводят к угнетению превращения фибриногена в фибрин-мономер и к подавлению тромбинопосредованной агрегации тромбоцитов [11]. Действие дезагрегантов, в свою очередь, также направлено на ингибирование активности тромбоцитов.…”