Agranulocytosis

1.     Scientific Advisor: Musaeva Begaiym

2.     Authored By: Vivek Tripathi

Vivek Gupta

Abhishek Yadav

1.Associate Professor, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.

2.Students, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.

Abstract

Agranulocytosis is a sudden and potentially life-threatening hematological disorder characterized by a profound reduction in circulating neutrophils, leaving patients dangerously vulnerable to infections. It often appears without warning, presenting as high fever, sore throat, or rapidly progressing sepsis. Despite its rarity, the condition carries a high mortality risk if not recognized and treated promptly. This review synthesizes evidence from major databases and hematology guidelines to outline the etiology, pathophysiology, and management of the disorder. Drug-induced cases account for the majority of etiologies, primarily through immune-mediated destruction or direct bone marrow suppression. Early intervention—including drug withdrawal, antimicrobial therapy, and the use of granulocyte colony-stimulating factor (G-CSF)—is essential to improve clinical outcomes.

Introduction

Agranulocytosis represents an acute hematological emergency characterized by the abrupt collapse of the neutrophil count. Unlike chronic leukopenic states, this condition typically strikes without a prodromal phase, leaving the host's immune system fundamentally compromised and defenseless against opportunistic and commensal bacteria. 

Clinical escalation can be rapid; fever is frequently the primary indicator, which, if ignored, can quickly progress to invasive infections, systemic septicemia, and multi-organ failure. Consequently, hospitalization and immediate clinical attention are standard requirements. Given that mortality rates increase sharply with diagnostic delays, early recognition remains a critical competency for clinicians across diverse specialties, including internal medicine, psychiatry, and endocrinology.

Etiology and Risk Factors

Agranulocytosis is most often acquired, with drug exposure being the dominant cause.

Major Causes

Drug-induced (70–90%)

1. Antithyroid drugs (methimazole, propylthiouracil)

2. Clozapine

3. Antibiotics (β-lactams, sulfonamides)

4. Antiepileptics

5. NSAIDs
   

1. Immune-mediated destruction

2. Bone marrow suppression

3. Infections (rare primary cause)

4. Idiopathic cases

Risk Factors

1. Advanced age

2. Female sex

3. Polypharmacy

4. Genetic susceptibility

5. Autoimmune disorders

6. Renal or hepatic impairment

Clinical Presentation

Symptoms often appear suddenly and progress rapidly:

1. High-grade fever

2. Severe sore throat

3. Oral ulcers and gingivitis

4. Skin and soft tissue infections

5. Pneumonia

6. Sepsis and septic shock (10–20%)

Importantly, signs of inflammation may be muted due to the absence of neutrophils, delaying recognition.

Laboratory Findings

1. Absolute neutrophil count (ANC):

○      < 0.5 × 10⁹/L (diagnostic)

○      < 0.1 × 10⁹/L (severe)

1. Hemoglobin: usually normal

2. Platelets: usually normal

3. Bone marrow:

○      Hypocellular granulocytic lineage

○      Maturation arrest (drug-induced)

Blood cultures: often positive during fever

Methodology

1. Databases searched: PubMed, PMC, Cochrane Library, WHO, BMJ

2. Study type: Narrative review

3. Articles screened: 140

4. Included: 65

5. Excluded: Case reports with insufficient data, duplicate studies

6. Focus areas:

○      Drug-induced mechanisms

○      Clinical outcomes

○      Role of G-CSF

○      Infection-related mortality

Discussion

Pathophysiology

Two mechanisms dominate:

1. Immune-mediated destruction of neutrophils

2. Direct toxic suppression of bone marrow

Infection Risk

Without neutrophils, bacterial and fungal infections spread rapidly. Fever should be treated as sepsis until proven otherwise.

Role of G-CSF

1. Accelerates neutrophil recovery

2. Shortens hospital stay

3. Reduces infectious complications

4. Does not increase adverse events

Challenges

1. Delayed diagnosis

2. Under-reporting

3. Lack of routine blood monitoring in high-risk drugs

Management

1. Immediate discontinuation of suspected drug

2. Protective isolation

3. Empirical broad-spectrum IV antibiotics

4. Antifungal therapy in prolonged neutropenia

5. G-CSF therapy

6. Supportive care and monitoring

Conclusion

Agranulocytosis is a rare but severe hematological emergency marked by sudden immune collapse and high infection-related mortality. Drug-induced cases dominate clinical practice, making medication history and routine blood monitoring critical. Early recognition, prompt withdrawal of the offending agent, aggressive antimicrobial therapy, and G-CSF administration dramatically improve patient outcomes.

Future strategies must focus on risk prediction, pharmacovigilance, genetic susceptibility, and standardized monitoring protocols to reduce preventable cases and associated mortality.