2. Value and limitations of laboratory testing:
Treatment options hinder on proper knowledge of the value of various
laboratory testing available and therefore these will be briefly
discussed. Examination of the patient’s coagulation and hematological
profile is critical, with the understanding that normal laboratory
values may not translate into clinical hemostasis. It is useful to know
the mechanism of action of the drug at hand and its effect on the
coagulation cascade to develop an understanding of the true usefulness
of blood tests (figure 1). For example, the international normalized
ratio (INR) was developed to monitor VKA and has limited value in
DOACs.18
The degree of anticoagulation and drug levels are of paramount
importance in determining the course of action. Typically, the
anticoagulant washes out after 5 half-lives have
elapsed,19 taking into account the patient’s
underlying renal and hepatic functions. Main advantages of DOACs include
their rapid onset of action (Cmax in most cases is 1-4 hours) and short
half-lives (9-15 hours, with the exception of betrixiban of 37 hours).
Thus, urgent reversal may not be necessary based on the pharmacokinetic
and pharmacodynamic properties of this class of anticoagulants (Table
1). However, several important issues should be considered when
evaluating blood tests:
-Prothrombin time (PT) : There is little correlation between PT
level and DOACs.18,20 PT is more reliable with higher
dabigatran levels.20
-Thrombin time (TT): A normal TT virtually excludes clinically
relevant dabigatran levels; however, subtherapeutic levels of dabigatran
may prolong TT and is most useful as a quantitative
tool.18
-Dilute thrombin time (dTT): measured by hemocolt, correlates
well with dabigatran levels and decreases the sensitivity of TT test by
diluting the patient’s sample with normal plasma.21
-Liquid chromatography or (Tandem mass spectrometry) :
is the gold standard for assessing DOAC activity; however, there is
minimal clinical outcome data and the test is not widely available in
clinical settings.18,22
-Ecarin Clotting Time: This clotting assay uses ecarin derived
from the saw-scaled viper and is used to measure the activity of direct
thrombin inhibitors such as dabigatran. This test relies on both the
prothrombin and fibrinogen in the patient’s sample and if abnormal can
result in issues with interpretation. The Ecarin Chromogenic
Assay is independent of variability in prothrombin and/or fibrinogen
levels and is not influenced by VKA.23
-Anti-Xa activity : The absence of anti-factor Xa activity
excludes any clinically significant drug levels, but the test may not be
widely available.24
-Thromboelastography (TEG) or Rotational thromboelastometry
(ROTEM) : assess platelet function. TEG and ROTEM may not detect
platelet defect due to ASA, dipyridamole or P2Y12receptor antagonists. Thrombin is generated in the TEG or ROTEM sample
cups and produces a false normal test despite the presence of clinical
coagulopathy.25