Influence of the direct oral anticoagulant dabigatran etexilate (Pradaxa®, Boehringer Ingelheim International GmbH) on routine coagulation assays (PT, aPTT and fibrinogen) is already thoroughly studied with different
reagent/instrument combinations [1]. We report a case of a known, but serious interference of dabigatran on the Fibrinogen-C XL assay (Instrumentation Laboratory) resulting in undetectable fibrinogen levels. The Fibrinogen-C XL assay is based on the Clauss method adding thrombin concentration reagent of+/- 35 UNIH/mL.

A 83-year-old man was sent to the emergency department with hyperkalemia secondary to acute kidney disease (eGFR 15.3 mL/min). In his medical history paroxysmal atrial tachycardia with a total atrioventricular block is described for which a pacemaker was implanted and dabigatran was initiated. On admission, his coagulation bilan revealed serious prolonged clotting times for the aPTT (105.7 s) and PT (INR 2.6), slightly elevated D-dimers (529 ng/mL), but no measurable fibrinogen level (<35 mg/dL). Based on these results, dabigatran administration was interrupted. During the next three days the aPTT and INR declined respectively to 56.9 s and 1.6, but the fibrinogen level remained unmeasurable.

Serious interference of dabigatran on the fibrinogen assay was suspected, however acquired hypofibrinogenemia could not be totally excluded. In patients with severe renal insufficiency (GFR<30 mL/min)
the half-life of dabigatran can be extended up to 27 h, resulting in a high trough level of 290.0 ng/mL in our patient after three days of stopping the treatment with dabigatran. Fibrinogen levels were reanalyzed with
different reagents (STA®-Liquid Fib (Stago) and QFA Thrombin (Instrumentation Laboratory)) resulting in normal to slightly elevated fibrinogen levels.

In conclusion, we showed a serious interference of dabigatran on the Fibrinogen-C XL assay in a patient with acute renal insufficiency, leading to spuriously low fibrinogen levels. With this report we want to warrant users of the Fibrinogen-C XL assay for the interference with dabigatran.

[1] Van Blerk M., Bailleul E., Chatelain B et al. Effect of dabigatran and rivaroxaban on routine coagulation assays. Thromb Haemost 2015; 113: 154–164

Analytical interference by dabigatran on Fibrinogen-C XL reagens resulting in spuriously low fibrinogen levels