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Agranulocytosis

Last edited: 4/14/2026

Overview

Agranulocytosis is a severe hematological emergency characterized by a profound and sudden decrease in circulating neutrophils, leading to increased susceptibility to infections and potentially fatal outcomes 123.

Diagnosis

  • Clinical Presentation: Rapid onset of fever, sore throat, and signs of infection with low absolute neutrophil count (<0.5 × 10^9/L) 12.
  • Laboratory Tests: Complete blood count (CBC) showing severe neutropenia, bone marrow examination may be necessary to rule out other causes 25.
  • Drug History: Detailed medication history to identify potential causative agents, particularly metamizole, calcium dobesilate, and other implicated drugs 139.

    • Management

  • Discontinuation of Suspected Drugs: Immediately discontinue any suspected drug causing agranulocytosis 13.
  • Empirical Antibiotics: Initiate broad-spectrum antibiotics to prevent or treat infections 214.
  • Granulocyte Colony-Stimulating Factor (G-CSF): Use G-CSF (e.g., GM-CSF at 300 μg/day or 5 μg/kg/day) to accelerate neutrophil recovery 1014.
  • Supportive Care: Intensive supportive care including hydration, monitoring for complications like neutropenic enterocolitis 18.

    • Special Populations

  • Elderly: Higher risk of severe complications; close monitoring and prompt intervention are crucial 2.
  • Pregnancy: Limited data; management should focus on safe discontinuation of offending agents and supportive care [No specific data in abstracts].

    • Key Recommendations

  • Immediate Drug Withdrawal: Discontinue any suspected drug causing agranulocytosis upon diagnosis (Evidence: Strong 13).
  • Initiate Broad-Spectrum Antibiotics: Start empirical antibiotic therapy to prevent or treat infections in patients with agranulocytosis (Evidence: Moderate 214).
  • Consider G-CSF Therapy: Use granulocyte colony-stimulating factor to accelerate neutrophil recovery in severe cases (Evidence: Moderate 1014).

    • References

    1 Hoffmann F, Bantel C, Jobski K. Agranulocytosis attributed to metamizole: An analysis of spontaneous reports in EudraVigilance 1985-2017. Basic & clinical pharmacology & toxicology 2020. link 2 Sing CW, Wong IC, Cheung BM, Chan JC, Chu JK, Cheung CL. Incidence and risk estimate of drug-induced agranulocytosis in Hong Kong Chinese. A population-based case-control study. Pharmacoepidemiology and drug safety 2017. link 3 Stammschulte T, Ludwig WD, Mühlbauer B, Bronder E, Gundert-Remy U. Metamizole (dipyrone)-associated agranulocytosis. An analysis of German spontaneous reports 1990-2012. European journal of clinical pharmacology 2015. link 4 Géniaux H, Assaf D, Miremont-Salamé G, Raspaud B, Gouverneur A, Robinson P et al.. Performance of the standardised MedDRA® queries for case retrieval in the French spontaneous reporting database. Drug safety 2014. link 5 Huber M, Andersohn F, Bronder E, Klimpel A, Thomae M, Konzen C et al.. Drug-induced agranulocytosis in the Berlin case-control surveillance study. European journal of clinical pharmacology 2014. link 6 Haerian K, Varn D, Vaidya S, Ena L, Chase HS, Friedman C. Detection of pharmacovigilance-related adverse events using electronic health records and automated methods. Clinical pharmacology and therapeutics 2012. link 7 Stadie N, Schröder A, Postler J, Lorenz A, Swoboda-Moll M, Burchert F et al.. Unambiguous generalization effects after treatment of non-canonical sentence production in German agrammatism. Brain and language 2008. link 8 Ibáñez L, Vidal X, Ballarín E, Laporte JR. Agranulocytosis associated with dipyrone (metamizol). European journal of clinical pharmacology 2005. link 9 Zapater P, Horga JF, García A. Risk of drug-induced agranulocytosis: the case of calcium dobesilate. European journal of clinical pharmacology 2003. link 10 Pavithran K, Thomas M. Hematopoietic growth factors in drug-induced agranulocytosis. The Journal of the Association of Physicians of India 2002. link 11 Naumann R, Felber W, Heilemann H, Reuster T. Olanzapine-induced agranulocytosis. Lancet (London, England) 1999. link03111-6) 12 Ballard KJ, Thompson CK. Treatment and generalization of complex sentence production in agrammatism. Journal of speech, language, and hearing research : JSLHR 1999. link 13 van der Klauw MM, Wilson JH, Stricker BH. Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994). American journal of hematology 1998. link1096-8652(199803)57:3<206::aid-ajh4>3.0.co;2-z) 14 Hurtado R, Candelaria M, Majluf-Cruz A, Sosa-Camas RE, Labardini-Méndez J. Drug-induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 1994. link 15 Tuschy U, Mühlan J. Methimazole and agranulocytosis--clinical study. Experimental and clinical endocrinology 1991. link 16 Lane GP, Speed B. Agranulocytosis after ranitidine administration. The Medical journal of Australia 1989. link 17 Hutchinson D, Wyld PJ. Sulphasalazine induced agranulocytosis. The New Zealand medical journal 1983. link 18 Rifkin GD. Neutropenic enterocolitis and Clostridium septicum infection in patients with agranulocytosis. Archives of internal medicine 1980. link 19 Kaplan B, Cardarelli C, Pinnell SR. Levamisole and agrandulocytosis. Cutis 1979. link 20 Eisner EV, Carr RM, MacKinney AR. Quinidine-induced agranulocytosis. JAMA 1977. link

    Original source

    1. [1]
      Agranulocytosis attributed to metamizole: An analysis of spontaneous reports in EudraVigilance 1985-2017. — Hoffmann F, Bantel C, Jobski K Basic & clinical pharmacology & toxicology (2020)
    2. [2]
      Incidence and risk estimate of drug-induced agranulocytosis in Hong Kong Chinese. A population-based case-control study. — Sing CW, Wong IC, Cheung BM, Chan JC, Chu JK, Cheung CL Pharmacoepidemiology and drug safety (2017)
    3. [3]
      Metamizole (dipyrone)-associated agranulocytosis. An analysis of German spontaneous reports 1990-2012. — Stammschulte T, Ludwig WD, Mühlbauer B, Bronder E, Gundert-Remy U European journal of clinical pharmacology (2015)
    4. [4]
      Performance of the standardised MedDRA® queries for case retrieval in the French spontaneous reporting database. — Géniaux H, Assaf D, Miremont-Salamé G, Raspaud B, Gouverneur A, Robinson P et al. Drug safety (2014)
    5. [5]
      Drug-induced agranulocytosis in the Berlin case-control surveillance study. — Huber M, Andersohn F, Bronder E, Klimpel A, Thomae M, Konzen C et al. European journal of clinical pharmacology (2014)
    6. [6]
      Detection of pharmacovigilance-related adverse events using electronic health records and automated methods. — Haerian K, Varn D, Vaidya S, Ena L, Chase HS, Friedman C Clinical pharmacology and therapeutics (2012)
    7. [7]
      Unambiguous generalization effects after treatment of non-canonical sentence production in German agrammatism. — Stadie N, Schröder A, Postler J, Lorenz A, Swoboda-Moll M, Burchert F et al. Brain and language (2008)
    8. [8]
      Agranulocytosis associated with dipyrone (metamizol). — Ibáñez L, Vidal X, Ballarín E, Laporte JR European journal of clinical pharmacology (2005)
    9. [9]
      Risk of drug-induced agranulocytosis: the case of calcium dobesilate. — Zapater P, Horga JF, García A European journal of clinical pharmacology (2003)
    10. [10]
      Hematopoietic growth factors in drug-induced agranulocytosis. — Pavithran K, Thomas M The Journal of the Association of Physicians of India (2002)
    11. [11]
      Olanzapine-induced agranulocytosis. — Naumann R, Felber W, Heilemann H, Reuster T Lancet (London, England) (1999)
    12. [12]
      Treatment and generalization of complex sentence production in agrammatism. — Ballard KJ, Thompson CK Journal of speech, language, and hearing research : JSLHR (1999)
    13. [13]
      Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994). — van der Klauw MM, Wilson JH, Stricker BH American journal of hematology (1998)
    14. [14]
      Drug-induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor. — Hurtado R, Candelaria M, Majluf-Cruz A, Sosa-Camas RE, Labardini-Méndez J Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion (1994)
    15. [15]
      Methimazole and agranulocytosis--clinical study. — Tuschy U, Mühlan J Experimental and clinical endocrinology (1991)
    16. [16]
      Agranulocytosis after ranitidine administration. — Lane GP, Speed B The Medical journal of Australia (1989)
    17. [17]
      Sulphasalazine induced agranulocytosis. — Hutchinson D, Wyld PJ The New Zealand medical journal (1983)
    18. [18]
      Neutropenic enterocolitis and Clostridium septicum infection in patients with agranulocytosis. — Rifkin GD Archives of internal medicine (1980)
    19. [19]
      Levamisole and agrandulocytosis. — Kaplan B, Cardarelli C, Pinnell SR Cutis (1979)
    20. [20]
      Quinidine-induced agranulocytosis. — Eisner EV, Carr RM, MacKinney AR JAMA (1977)
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