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