Skip to main content

Advertisement

SpringerLink
Log in

Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals

  • Special Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aims

Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data.

Methods

A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 April 2005). Using a computerized process and hematology laboratory data, all neutrophil counts with a value less than 500/mm3 were registered, allowing identification of inpatients suffering from agranulocytosis during the period of the study. Medical records of all selected patients were then consulted. Cytostatic drugs were excluded from this study.

Results

During the period of the study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835 (1.26%) had a neutrophil count less than 500/mm3, corresponding to 739 patients. Seventeen patients were excluded because of lack of data, and 20 cases of infants younger than 3 months were excluded. Among the remaining patients (n = 702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were suspected. All cases were classified as “serious” since they led to death in 2 cases, hospitalization or prolongation of hospitalization in 19 cases and threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done in all cases with regression of neutropenia in 21 cases. According to hospitalization data, the annual incidence of drug-induced agranulocytosis was 1.62 (1.0–2.6) per 10,000 inpatients in Toulouse University hospital (based on 534 cases) and 3.24 (0.9–8.3) per 10,000 inpatients in Navarra University Hospital (based on 168 cases). The involved drugs were mainly antibacterial (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse University Hospital were spontaneously reported by physicians during the same period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France.

Conclusion

Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Medina PJ, George JN (2001) Drug-associated blood dyscrasias. Adv Drug React Bull 210:803–806

    Article  Google Scholar 

  2. Kaufman DW, Kelly JP, Levy M, Shapiro S (1991) The drug etiology of agranulocytosis and aplastic anemia. Oxford University Press, New York

    Google Scholar 

  3. Theophile H, Begaud B, Martin K, Laporte JR, Capella D (2004) Incidence of agranulocytosis in southwest France. Eur J Epidemiol 19:563–565

    Article  PubMed  Google Scholar 

  4. Andrès E, Maloisel F (2006) Idiosyncratic drug-induced agranulocytosis. Rev Med Int 27:209–214

    Article  Google Scholar 

  5. Strom BL, Carson JL, Schinnar R, Snyder ES, Shaw M (1992) Descriptive epidemiology of agranulocytosis. Arch Intern Med 152:1475–1480

    Article  PubMed  CAS  Google Scholar 

  6. Young NS (1994) Agranulocytosis. JAMA 271:935–938

    Article  PubMed  CAS  Google Scholar 

  7. Kaufman DW, Kelly JP, Jurgelon JM et al (1996) Drugs in the aetiology of agranulocytosis and aplastic anaemia. Eur J Haematol Suppl 60:23–30

    PubMed  CAS  Google Scholar 

  8. Julia A, Olona M, Bueno J et al (1991) Drug induced agranulocytosis: pronostic factors in a series of 168 episodes. Br J Haematol 79:366–371

    PubMed  CAS  Google Scholar 

  9. Ibanez L, Juan J, Perez E, Carne X, Laporte J-R (1991) Agranulocytosis associated with aprindine and other antiarrhythmic drugs: an epidemiological approach. Eur Heart J 12:639–641

    PubMed  CAS  Google Scholar 

  10. Strom BL, Carson JL, Schinnar R, Snyder ES, Shaw M, Lundin FE (1993) Nonsteroidal anti-inflammatory drugs and neutropenia. Arch Intern Med 153:2119–2124

    Article  PubMed  CAS  Google Scholar 

  11. Rawson NSB, Harding SR, Malcolm E, Lueck L (1998) Hospitalizations for aplastic anemia and agranulocytosis in Saskatchewan: incidence and associations with antecedent prescription drug use. J Clin Epidemiol 51:1343–1355

    Article  PubMed  CAS  Google Scholar 

  12. Van der Klauw MM, Goudsmit R, Halie MR et al (1999) A population-based case-cohort study of drug-associated agranulocytosis. Arch Intern Med 159:369–374

    Article  PubMed  Google Scholar 

  13. Laporte JR, Capella D, Juan J (1990) Agranulocytosis induced by cinepazide. Eur J Clin Pharmacol 38:387–388

    Article  PubMed  CAS  Google Scholar 

  14. Ibanez L, Ballarin E, Perez E, Vidal X, Capella D, Laporte JR (2000) Agranulocytosis induced by pyrithyldione, a sedative hypnotic drug. Eur J Clin Pharmacol 55:761–764

    Article  PubMed  CAS  Google Scholar 

  15. Ibanez L, Ballarin E, Vidal X, Laporte JR (2000) Agranulocytosis associated with calcium dobesilate: clinical course and risk estimation with the case-control and the case-population approaches. Eur J Clin Pharmacol 56:763–767

    Article  PubMed  CAS  Google Scholar 

  16. Ibanez L, Vidal X, Ballarin E, Laporte JR (2005) Population-based drug-induced agranulocytosis. Arch Intern Med 165:869–874

    Article  PubMed  CAS  Google Scholar 

  17. Benichou Ch (1994) Adverse drug reactions: a practical guide to diagnosis and management. Wiley, Chichester

    Google Scholar 

  18. No authors listed (1991) Standardization of definitions and criteria of causality assessment of adverse drug reactions. Drug-induced cytopenia. Int J Clin Pharmacol Ther Toxicol 29:75–81

    Google Scholar 

  19. Cancer Therapy Evaluation Program (2003) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. http://www.ctep.cancer.gov/forms/CTCAEv3.pdf

  20. Uppsala Monitoring Centre (2006) The use of the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardised case causality assessment. http://www.who-umc.org/graphics/4409.pdf

  21. Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–59

    Article  PubMed  CAS  Google Scholar 

  22. Anonymous (2006) Dictionnaire VIDAL, 82th edn. OVP, Paris

  23. No authors listed (2005) Catálogo de especialidades farmacéuticas. Consejo General de Colegios de Farmacéuticos, Madrid

  24. Tubert P, Bégaud B, Péré JC, Haramburu F, Lellouch J (1992) Power and weakness of spontaneous reporting: a probabilistic approach. J Clin Epidemiol 45:283–286

    Article  PubMed  CAS  Google Scholar 

  25. Haramburu F (1993) Estimation of under-reporting. Methodological approaches in pharmacoepidemiology: application to spontaneous reporting ARME-P. Elsever, Amsterdam

    Google Scholar 

  26. Thürmann P (2001) Methods and systems to detect adverse drug reactions in hospitals. Drug Saf 24:961–968

    Article  PubMed  Google Scholar 

  27. Azaz-Livshits T, Levy M (1998) Computerized surveillance of adverse drug reactions in hospital: a pilot study. Br J Clin Pharmacol 45:309–314

    Article  PubMed  CAS  Google Scholar 

  28. Tegeder I, Levy M, Muth-Selbach U (1999) Retrospective analysis of the frequency and recognition of adverse reactions by means of automatically recorded laboratory signals. Br J Clin Pharmacol 47:557–564

    Article  PubMed  CAS  Google Scholar 

  29. Bagheri H, Michel F, Lapeyre-Mestre M et al (2000) Detection and incidence of drug-induced liver injuries in hospital: a prospective analysis from laboratory signals. Br J Clin Pharmacol 50:479–484

    Article  PubMed  CAS  Google Scholar 

  30. Levy M, Azaz-Livshits T, Sadan B et al (1999) Computerized surveillance of adverse reactions in hospital: implementation. Eur J Clin Pharmacol 54:887–892

    Article  PubMed  CAS  Google Scholar 

  31. Salame G, Péré JC, Chaslerie A et al (1990) Liver injuries: a prospective study (abstract). J Clin Res Pharmacoepidemiol 4:133

    Google Scholar 

  32. Dugué A, Bagheri H, Lapeyre-Mestre M, Tournamille JF et al (2004) Detection and incidence of muscular adverse drug reactions: a prospective analysis from laboratory signals. Eur J Clin Pharmacol 60:285–292

    Article  PubMed  CAS  Google Scholar 

  33. Andersohn F, Bronder E, Klimpel A, Garbe E (2004) Proportion of drug-related serious rare blood dyscrasias: estimates from the Berlin Case-Control Surveillance Study. Am J Hematol 77 :316–318

    Article  PubMed  Google Scholar 

  34. Assurance Maladie en ligne (2006) Les médicaments remboursés en 2003 et 2004 par le régime général d’Assurance maladie. http://www.ameli.fr/244/DOC/2333/article.html

  35. IMS (2006) Pharmaceutical market intelligence. http://www.imshealth.com

  36. The International Agranulocytosis and Aplastic Anemia Study (1986) Risk of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. JAMA 256:1749–1757

    Article  Google Scholar 

  37. Classen DC, Pestotnik SL, Evans RS, Bruke JP (1991) Computerized surveillance of adverse drug events in hospital patients. JAMA 266:2847–2851

    Article  PubMed  CAS  Google Scholar 

  38. Bates DW, O’Neil AC, Boyle D, Teich J, Chertow GM, Komaroff AL, Brennan TA (1994) Potential identifiability and preventability of adverse events using information systems. J Am Med Inform Assoc 1:404–411

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’informations sur le Médicament, Unité de Pharmacoépidémiologie EA 3696, Université Paul Sabatier, Faculté de Médecine, Toulouse, France

    N. Tavassoli, A. Sommet, M. Lapeyre-Mestre, J. L. Montastruc & H. Bagheri

  2. Laboratoire d’Hématologie, Centre Hospitalier Universitaire, Hôpital Purpan, Toulouse, France

    E. Duchayne & P. Sie

  3. Department of Clinical Pharmacology, University Hospital of Navarra, Pamplona, Spain

    B. Sadaba, M. J. Muoz & J. Honorato

  4. Département d’information médicale, Centre Hospitalier Universitaire, Hôtel Dieu Saint-Jacques, Toulouse, France

    K. Desboeuf

  5. Service de Pharmacologie Clinique, Université Paul Sabatier, Faculté de Médecine, 37 allées Jules Guesde, 31000, Toulouse, France

    H. Bagheri

Authors
  1. N. Tavassoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Duchayne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Sadaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Desboeuf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Sommet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Lapeyre-Mestre
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. J. Muoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. Sie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. Honorato
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. L. Montastruc
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H. Bagheri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Bagheri.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tavassoli, N., Duchayne, E., Sadaba, B. et al. Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals. Eur J Clin Pharmacol 63, 221–228 (2007). https://doi.org/10.1007/s00228-006-0242-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-006-0242-8

Keywords

Search

Navigation