Question 1 · Hard
An 84-year-old man taking dabigatran 150 mg twice daily for atrial fibrillation is admitted with melena and acute kidney injury (eGFR 16 mL/min/1.73 m²). Results: PT 19.0 s (reference 11.0-13.5 s), APTT 78 s (25-35 s), thrombin time over 150 s (14-19 s), reptilase time 17 s (15-20 s), heparin-calibrated anti-Xa below 0.10 IU/mL, platelets 230 × 10^9/L and D-dimer normal. Fibrinogen is 1.1 g/L (110 mg/dL) by the Clauss method but 3.9 g/L by the PT-derived method, and fibrinogen antigen is 3.7 g/L (reference 2.0-4.0 g/L). The most likely cause of the low Clauss result is:
- AHeparin contaminating the sample
- BDabigatran inhibiting the Clauss thrombin
- CFibrinogen consumption by DIC
- DA dysfunctional fibrinogen molecule
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Answer: B · Dabigatran inhibiting the Clauss thrombin
The thrombin time is grossly prolonged while the reptilase time, which uses a snake-venom enzyme that thrombin inhibitors do not block, is normal: the fibrinogen clots normally and something is inhibiting thrombin. The heparin-calibrated anti-Xa below 0.10 IU/mL excludes heparin, which leaves dabigatran, which has accumulated because it is cleared mainly by the kidneys. At very high drug levels, dabigatran can inhibit the reagent thrombin in some Clauss methods and give a falsely low fibrinogen, while the antigen and PT-derived results show that fibrinogen is adequate. A dysfibrinogenemia would prolong the reptilase time too, and DIC would lower the antigen and platelets and raise the D-dimer. A dabigatran level by diluted thrombin time or ecarin assay should be measured, and cryoprecipitate should not be given on the Clauss result alone.
- A: A heparin-calibrated anti-Xa below 0.10 IU/mL excludes heparin.
- C: Platelets, D-dimer and fibrinogen antigen are normal, so nothing is being consumed.
- D: A dysfibrinogen would prolong the reptilase time too, and it is normal.