| Abstract (english) | Direct oral anticoagulants (DOACs) are drugs that have been increasingly
used for the prevention and treatment of tromboembolic diseases in the past
decade. According to the mechanism of action, they are divided into two groups:
1. direct inhibitor of thrombin or activated coagulation factor II (FIia) that
includes dabigatran (Pradaxa®, Boehringer Ingelheim) and 2. direct inhibitors
of activated factor X (FXa) that include rivaroxaban (Xarelto®, Bayer), apixaban
(Eliquis®, Pfizer) and edoxaban (Lixiana®, Daiichi-Sankyo). At present, ali
four drugs are licensed for the prevention of venous thromboembolism (VTE)
in patients undergoing orthopedic knee or hip replacement surgery, for prevention
of stroke and systemic embolism in patients with non-valvular atrial
fibrillation (NVAF) and for prevention and treatment of VTE including deep
vein thrombosis (DVT) and noncomplicated pulmonary embolism (PE). These
drugs have rapid onset and offset of action, more predictable pharmacokinetic
and pharmacodynamic properties, equal or superior efficacy and improved
safety for the patient compared to the vitamin K antagonists (VKAs) that have
been used for decades as the only available oral anticoagulants. In contrast to
VKAs, DOACs are administered in a fixed <lose and no routine coagulation
monitoring is required for these drugs. However, despite of their advantages
compared to VKAs, DOACs also have an increased risk of bleeding as the most
important side effect of treatment. Although it is generally accepted view that
clinical application of DOACs does not require frequent laboratory control
because the medication dosage is not based on the results of laboratory tests,
the results of first clinical experiences also dispute the fact that the treatment
with DOACs completely excludes the need for laboratory diagnostics. The
growing clinical experience with these drugs during several years strongly suggests
that there are special clinical circumstances and patient populations in
which laboratory measurement of DOACs should be performed, including
bleeding or thromboembolic events, invasive diagnostic procedures or surgery,
extremes of body weight and suspected 11011-compliance or overdose. Treatment
of patients with DOACs has a significant impact on the results of commonly
used screening coagulation assays i.e., prothrombin time (PT), activated
partial thromboplastin time (APTT) and thrombin time (TT). However, due to
significant differences in the sensitivity of individual commercial reagents for
these screening coagulation tests in relation to a particular DOAC drug, these
assays are not appropriate for reliable assessment of their anticoagulant effect,
but rather exclusively for rough estimation of the drug dosage in emergency
situations of the life-threatening patients. Among screening coagulation assays,
the result of PT test is influenced by FXa inhibitors, while dabigatran affects the
results of APTT and TT assays. Knowing the impact of DOACs on the results
of screening coagulation assays (PT, APTT, TT) is a precondition for the correct
interpretation of the test results. With the introduction of DOACs in clinical
practice, the major challenge in the field of laboratory medicine was to find and
introduce appropriate methods for assessment of anticoagulant effects of these
medications. Thus, simultaneously with the first clinical experiences in application
of DOACs, research has also been focused on the development of specific
coagulation methods that allow quantitative determination of concentration
of these drugs. Coagulometric and chromogenic methods have been
designed as quantitative methods for measuring the concentration of individual
DOACs in plasma. Dabigatran concentrations can be determined by coagulometric
methods (diluted TT and ecarin clotting time assays) as well as
with the newer chromogenic methods (chromogenic ecarin assay and anti-Ila
assay), whereas quantitative methods for determination the concentration of
direct FXa inhibitors include exclusively chromogenic anti-Xa method using
calibration with appropriate drug. These quantitative methods have been so far
applied in research related to DOACs exclusively, but they only are becoming
commercially available, and their implementation in specialized coagulation
laboratories for now is still at the very beginning. lt is excepted that the application
of specific quantitative methods for measuring the concentration of
DOACs will be a great support and help in making clinical decisions in certain
clinical situations. However, because many unknowns associated with the use
of these drugs are still present, it is a long journey of research to enable DOACs
to completely replace the old anticoagulants. |
