2. Value and limitations of laboratory testing:
Examination of the patient’s coagulation and hematological profiles is
critical; however; treatment options hinge upon proper knowledge of the
usefulness of various laboratory testing available. Normal laboratory
values are usually reassuring but may not always translate into clinical
hemostasis. It is helpful 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 value and usefulness of various blood tests
(Figure 1). For example, the international normalized ratio (INR) was
developed to monitor VKAs and has limited value in
DOACs.11
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, taking into
account the patient’s underlying renal and hepatic functions
(Table1).12 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).
In addition, the pharmacodynamic effect of this class of anticoagulants
is even shorter, unlike warfarin that has a much longer pharmacodynamic,
compared to its pharmacokinetic, half-life. Thus, urgent reversal of
DOAC agents may not always be necessary; however, in emergency cases,
monitoring of DOAC levels might be helpful, with several important
considerations to take note of when evaluating laboratory values:
-Prothrombin time (PT) : There is little correlation between PT
level and DOACs.11,13 PT is more reliable with higher
dabigatran levels.13
-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.11
-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.14
-Liquid chromatography or (Tandem mass spectrometry) :
is the gold standard for assessing DOAC concentration; however, there is
minimal clinical outcome data and the test may not be widely available
in clinical settings.11,15
-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.16
-Anti-Xa activity : The absence of anti-factor Xa activity
excludes any clinically significant drug levels, but the test may not be
widely available.17
-Thromboelastography (TEG) or Rotational thromboelastometry
(ROTEM) : Thrombin is generated in the TEG or ROTEM sample cups and may
produce a false normal test despite the presence of clinical
coagulopathy. TEG and ROTEM may not detect platelet defect due to ASA,
dipyridamole or P2Y12 receptor antagonists. A
dose-dependent increase in ROTEM clotting time was noted for DOACs and
low levels of edoxaban, rivaroxaban or dabigatran only poorly impacted
ROTEM tests. Apixaban had only a low effect even at high
concentrations.18
-Quantra QPlus : A novel point-of-care platform that uses
ultrasonic pulses to characterize dynamic changes in viscoelastic
properties of a blood sample during coagulation. In a prospective study,
the Quantra predicted clinical need for platelet transfusion but not for
fresh frozen plasma (FFP).19