How does dabigatran (Pradaxa) affect Prothrombin Time (PT)/International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT)?

Effect of Dabigatran on PT/INR and aPTT

Dabigatran has little effect on PT/INR at clinically relevant plasma concentrations, making these tests unsuitable for assessing its anticoagulant activity, while it causes a curvilinear prolongation of aPTT that can provide a qualitative assessment of drug presence but not precise quantification. 1, 2

Effects on aPTT

• Dabigatran produces a concentration-dependent prolongation of aPTT with a non-linear (curvilinear) relationship, especially at higher concentrations (≥200 ng/mL) 1
• At peak concentration, aPTT levels can be approximately twofold that of normal levels, and may still be as high as 1.5 times normal levels after 12 hours 1
• The median trough aPTT in patients receiving the standard 150 mg dose was 52 seconds (range: 40-76 seconds) in the RE-LY trial 2
• A normal aPTT does not exclude dabigatran levels in the 'on therapy' range, but when using a sensitive assay, it can exclude drug levels above the therapeutic range 1
• The sensitivity of aPTT to dabigatran varies significantly between different reagents, which affects interpretation 1, 3

Effects on PT/INR

• Dabigatran has minimal effect on PT and INR at clinically relevant plasma concentrations 1, 2
• PT/INR is relatively insensitive to dabigatran exposure and cannot be interpreted in the same way as for warfarin monitoring 2
• Point-of-care INR devices developed for vitamin K antagonist monitoring may give falsely elevated readings in patients taking dabigatran and should not be used 1, 4
• In a study comparing laboratory and point-of-care INR measurements, at therapeutic dabigatran concentrations (60-275 ng/mL), point-of-care INR values increased from 1.7 to 4.0, versus only 1.1 to 1.5 with laboratory methods 4

More Specific Tests for Dabigatran Monitoring

• The thrombin time (TT) is extremely sensitive to dabigatran and a normal TT excludes even very low levels of the drug 1, 3
• However, TT is too sensitive for quantification of therapeutic or above-therapeutic levels (a level of 60 ng/mL can result in TT >300 seconds) 1, 3
• Diluted thrombin time (dTT) and ecarin chromogenic assay (ECA) display a direct linear relationship with dabigatran concentration and are suitable for quantitative assessment 1
• In the RE-LY trial, the median trough ECT in patients receiving the 150 mg dose was 63 seconds (range: 44-103 seconds) 2

Clinical Implications

• For emergency situations (bleeding, urgent procedures), routine coagulation tests can quickly inform clinicians about recent dabigatran exposure 1
• When monitoring is needed, institutions should consider having specific dabigatran assays (dTT/ECA) available 24/7 for emergency situations 1
• In trauma settings, aPTT values exceeded the threshold for coagulopathy in 100% of patients on dabigatran in one study, compared to 63% of patients on anti-Xa inhibitors 1
• Dabigatran affects the activities of multiple coagulation factors, including factors II, V, VIII, and IX, as well as antifactor VIII inhibitor 5

Important Caveats

• The timing of blood sampling relative to dabigatran administration is crucial for interpretation, as maximum effect occurs at peak plasma concentration (1-3 hours after intake) 1
• A normal aPTT has limited value in emergency settings, especially if measured outside the peak plasma drug concentration window 1
• For accurate quantification of dabigatran levels, calibrated specific assays (dTT/ECA) should be used rather than routine coagulation tests 1, 6
• In patients with renal impairment, the effect of dabigatran on coagulation tests may be more pronounced and prolonged due to reduced clearance 2