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