Acute pulmonary emboli in a patient on long-term dabigatran therapy.

OBJECTIVE: To describe the case of a patient who developed acute pulmonary emboli (PE) despite long-term anticoagulation with dabigatran. CASE SUMMARY: A 69-year-old obese woman was hospitalized for worsening shortness of breath, dyspnea on exertion, and left pleuritic chest pain. On admission, a computed tomography angiogram revealed acute bilateral PE, despite use of dabigatran for atrial fibrillation for approximately 5 years prior to admission. Dabigatran was stopped and therapeutic enoxaparin was initiated concomitantly with warfarin. An investigation into possible causes for the development of the PE, including hypercoagulability, was unrevealing. Since dabigatran should have protected against PE, the patient was questioned regarding adherence to her regimen. She stated that she was adherent but reported using a pillbox. The patient was discharged home on warfarin with an enoxaparin bridge until her international normalized ratio was at least 2.0. DISCUSSION: The underlying cause for the patient's acute PE is unknown but could possibly be attributed to obesity and reduced mobility. Although dabigatran should have prevented PE, the presence of interacting drugs, patient-specific pharmacokinetics, suboptimal medication storage, and laboratory abnormalities may have resulted in reduced dabigatran exposure and protection. This is a reasonable hypothesis; however, the patient did not develop a stroke while receiving dabigatran. CONCLUSIONS: Our patient developed acute bilateral PE despite receiving long-term anticoagulation with dabigatran. While it is possible that patient-specific factors resulted in reduced dabigatran exposure and efficacy, conclusions cannot be made.

Evidence for the presence of active cytochrome P450 systems in Schistosoma mansoni and Schistosoma haematobium adult worms.

Extracts of the adult worms of both Schistosoma mansoni and Schistosoma haematobium can metabolise some typical P450 substrates but to differing degrees. S. mansoni worm extracts displayed a approximately 12-fold higher specific activity for an aminopyrine substrate than rat liver microsomes. At 4 mM substrate concentration the demethylation reaction with N-nitrosodimethylamine (NDMA) (5 nmol HCHO/mg protein/min) was only half that of rat liver microsomes, whereas in extracts of S. haematobium, no detectable activity was found towards NDMA. Using ethylmorphine as substrate the demethylation activity of S. mansoni extracts (1.82 nmol HCHO/mg protein/min) was 5.5-fold lower than that of rat liver microsomes. Benzphetamine demethylase activity was also readily detectable in S. mansoni worm extracts at 6.79 nmol HCHO/mg protein/min compared with 10.20 nmol HCHO/mg protein/min in the case of rat liver microsomes. When aniline was used as substrate, surprisingly, no activity was found in worm extracts of either S. mansoni or S. haematobium, whereas rat liver microsomes showed high activity towards this amine. The anti-P450 2E1 and 2B1/2 cross-reacted with both worm homogenates and gave a specific band corresponding to a protein of molecular weight of approximately 50.0 kDa. A study with anti-P450 IVA antibody revealed that while this protein was strongly expressed in S. haematobium worm extracts, no immunoreactivity was observed with extracts of S. mansoni. Immunoblotting analyses with anti-P450 IIIA and P450 1A1 did not detect immunoreactive protein in either S. mansoni or S. haematobium.