Journal of Thrombosis and Thrombolysis

, Volume 45, Issue 4, pp 588–592 | Cite as

Acute agranulocytosis after oral administration of dabigatran: a rare case report and a short review of literature

  • Sergio Fasullo
  • Stefania Davì
  • Gioacchino Cosenza
  • Francesca Di Franco
  • Nicola La Manna
  • Alfonso Giubilato
  • Graziella Vetrano
  • Giorgio Maringhini


This case report describes agranulocytosis immediately after oral administration of dabigatran in a 68 years old man with atrial fibrillation (AF). Dabigatran is an oral, reversible and competitive thrombin inhibitor that has shown promising results. In patients with atrial fibrillation of RE-LY study (Randomized Evaluation of Long-Term Anticoagulant Therapy), dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. Dabigatran is administered as a prodrug and the peak of the plasma concentrations occurs within 2 h of ingestion. Agranulocytosis is characterized by a severe decrease or lack of circulating granulocytes. This rare event can be found among people taking dabigratan, especially for people who are female, over the age of 60, who took the drug for < 1 month. Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. The patient’s white blood cell count increased abruptly after discontinuation of the drug, suggesting an immune response caused by dabigatran. Although anticoagulant drugs are commonly used to treat atrial fibrillation, attention should be paid to this aspect and possible drug interactions.


Agranulocitosis Dabigratan Atrial fibrillation 



I would like to express my gratitude for the patients, without whom the profession itself would have no reason to be. We thank all the nurses of the cardiology staff (in particular Mr. Antonio Miserendino) for continued help in the most critical moments of charitable and Dr. Vincenzo Bucca, Dr. Fernada Pipitone, Dr. Maria Gabriella Vitrano, Dr. Arcangelo Giamporcaro and Dr. Pietro Di Pasquale for suggestions.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest.


  1. 1.
    Larsen TB, Rasmussen LH, Skjøth F et al (2013) Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 61(22):2264–2273CrossRefPubMedGoogle Scholar
  2. 2.
    Seeger JD1, Bykov K, Bartels D et al (2015) Safety and effectiveness of dabigatran and warfarin in routine care of patients with atrial fibrillation. Thromb Haemost 114(6):1277–1289PubMedGoogle Scholar
  3. 3.
    Pradaxa and Agranulocytosis—from FDA reports as at Jan 2018;
  4. 4.
    EMA—European database of suspected adverse drug reaction reports, as at Jan 2018;
  5. 5.
    Pisciotta V (1978) Drug-induced agranulocytosis. Drugs 15:132–143CrossRefPubMedGoogle Scholar
  6. 6.
    Van Ryn J, Stangier J, Haertter S et al (2011) Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103(6):1116–1127Google Scholar
  7. 7.
    Stangier J (2008) Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 47(5):285–295CrossRefPubMedGoogle Scholar
  8. 8.
    Blech S, Ebner T, Ludwig-Schwellinger E et al (2008) The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 36(2):386–399CrossRefPubMedGoogle Scholar
  9. 9.
    Pradaxa (2001) Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT; drugsatfda_docs/label/2011/022512s004lbl.pdf
  10. 10.
    Andrès E, Zimmer J, Affenberger S et al (2006) Idiosyncratic drug-induced agranulocytosis: update of an old disorder. Eur J Intern Med 17:529–535CrossRefPubMedGoogle Scholar
  11. 11.
    Andersohn F, Konzen C, Garbe E (2007) Nonchemotherapy drug-induced agranulocytosis: a systematic review of case reports. Ann Intern Med 146:657–665CrossRefPubMedGoogle Scholar
  12. 12.
    Andrès E, Maloisel F (2008) Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol 15(1):15–21CrossRefPubMedGoogle Scholar
  13. 13.
    Tesfa D, Keisu M, Palmblad J (2009) Idiosyncratic drug-induced agranulocytosis: possible mechanisms and management. Am J Hematol 84(7):428–434CrossRefPubMedGoogle Scholar
  14. 14.
    Pisciotta AV (1973) Immune and toxic mechanisms in drug-induced agranulocytosis. Semin Hematol 10:279–310PubMedGoogle Scholar
  15. 15.
    Salama A, Schutz B, Kiefel V et al (1989) Immune-mediated agranulocytosis related to drugs and their metabolites:mode of sensitization and heterogeneity of antibodies. Br J Haematol 72:127–132CrossRefPubMedGoogle Scholar
  16. 16.
    Andersohn F, Konzen C, Garbe E (2007) Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 146:657–665CrossRefPubMedGoogle Scholar
  17. 17.
    Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151CrossRefPubMedGoogle Scholar
  18. 18.
    Hankey GJ, Eikelboom JW (2001) Dabigatran etexilate: a new oral thrombin inhibitor. Circulation 123:1436–1450CrossRefGoogle Scholar
  19. 19.
    Hayashi H, Kitoh K, Mitsunami K et al (2012) Agranulocytosis immediately oral admistraion cibenzoline and dabigatran in a patient with paroxysmal atrial fibrillation. Intern Med 51:1987–1990CrossRefPubMedGoogle Scholar
  20. 20.
    Ibáñez L, Vidal X, Ballarín E et al (2005) Population-based drug-induced agranulocytosis. Arch Intern Med 165(8):869–874CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Coronary Care Unit, “O.Barberi”, “G.F.Ingrassia” HospitalPalermoItaly
  2. 2.Chemistry and Pharmaceutical TechnologiesPalermoItaly
  3. 3.Department Cardiology “Paolo Borsellino”“G.F.Ingrassia” HospitalPalermoItaly

Personalised recommendations