Granulocytopenia
Basics
Description
Description
- A significant decrease in the number of granulocytes in the peripheral blood
- 3 classes of granulocytes:
- Neutrophils or polymorphonuclear (PMN) cells and bands
- Eosinophils
- Basophils
- As PMN cells predominate, the term neutropenia is often used interchangeably with granulocytopenia, as almost all granulocytopenic patients are neutropenic
- Leucocyte count:
- Normal range 4,500/mm311,000/mm3
- Four basic mechanisms cause granulocytopenia:
- Decreased production
- Ineffective granulopoiesis
- Shift of circulating PMN cells to vascular endothelium
- Enhanced peripheral destruction
- The risk of complications of granulocytopenia increases dramatically with falling levels of the absolute neutrophil count (ANC)
- Neutropenia:
- Usually defined in clinical practice by an ANC <1,400/mm3
- ANC = WBC × percentage (PMN + bands)
- Modern automated instruments often calculate and report ANC
- Risk of infection increases rapidly once the neutrophil count falls below 1,000 cells/mm3
- The National Cancer Institute (NCI) criteria for medication adverse hematologic event uses a 4-grade system
- NCI grade 1: Lower limit of normal to 1,500
- Mild neutropenia or NCI grade 2: 1,000–1,500
- Moderate neutropenia or NCI grade 3: Between 500–1,000
- Severe neutropenia or NCI grade 4: <500
- Agranulocytosis:
- ANC <100
- Most often due to drug reaction
- Risk of infection is also influenced by the underlying cause of neutropenia, the bone marrow myeloid reserve, and risk factors for infection
- Patients with a count <1,000 that has recently or rapidly fallen are at greater risk for infection than those with a rising count <500
- Patients with myelodysplastic syndromes should be considered granulocytopenic with higher counts because of defective neutrophils
- Mortality of fever and neutropenia is as high as 50% if untreated:
- Mortality correlates with the duration and severity of the neutropenia and the time elapsed until the first dose of antibiotics
- When treated, inpatient mortality rate at 6.6%
- 16% of patients on chemotherapy will experience at least on episode of febrile neutropenia
- Unexplained fever is the most common presentation of febrile neutropenia:
- Only 20%–30% have a clinically detectable infection in the ED
- 21% of patients with cancer and neutropenic fever develop serious complications
Pediatric Considerations
- Severe congenital neutropenia:
- Heterogeneous genetic disorders
- Severe forms present with stomatitis or recurrent bacterial infections
- Newborn infants have a physiologically elevated ANC in the first few days of life and may be granulocytopenic with levels >1,500/mcL
- Children >3 mo with isolated neutropenia without immunodeficiency or a central venous catheter are at low risk of serious bacterial infection
Etiology
Etiology
- Myelosuppressive drug therapy or radiation treatment for neoplasms
- Most common 5–10 d after chemo
- Adverse reaction to drugs (second most common cause):
- Discontinuation usually results in resolutions within 30 d
- Nonchemotherapy medications:
- Clozapine
- Dapsone
- Hydroxychloroquine
- Infliximab
- Lamotrigine
- Methimazole
- Oxacillin
- Penicillin G
- Procainamide
- Propylthiouracil
- Quinidine/quinine
- Rituximab
- Sulfasalazine
- Trimethoprim–sulfamethoxazole
- Vancomycin
- Drugs with the highest risk:
- Antipsychotic: Clozapine
- Antibiotic: Sulfasalazine
- Antithyroid: Thioamides
- Antiplatelet agents
- Antiepileptic drugs
- NSAIDs
- Drugs that suppress the bone marrow:
- Methotrexate
- Cyclophosphamide
- Colchicine
- Azathioprine
- Ganciclovir
- Chemicals
- Bacterial infections:
- Typhoid
- Shigella enteritis
- Brucellosis
- Tularemia
- Tuberculosis
- Parasitic infections:
- Kala azar
- Malaria
- Rickettsial infections:
- Rickettsialpox
- Ehrlichiosis
- Rocky Mountain spotted fever
- Viral infections:
- HIV
- Hepatitis B
- Epstein–Barr viral infections
- Respiratory syncytial virus
- Cytomegalovirus
- Immune-related:
- Primary immune neutropenia:
- Due to antineutrophil antibodies
- Crohn disease
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Goodpasture disease
- Wegener granulomatosis
- Thymoma
- Compliment activation
- Primary immune neutropenia:
- Bone marrow infiltration
- Transfusion reaction
- Alcoholism:
- Bone marrow suppression
- Splenic sequestration in patients with enlarged spleen secondary to portal hypertension
- Hypersplenism most commonly due to liver disease with portal hypertension
- Vitamin deficiency (B12/folate/copper)
- Chronic idiopathic neutropenia
- Pure white cell aplasia
Pediatric Considerations
- Congenital neutropenia:
- Neutropenia with abnormal immunoglobulins
- Reticular dysgenesis
- Severe congenital neutropenia or Kostmann syndrome
- Cyclic neutropenia
- Chronic benign neutropenia
- Neonatal isoimmune neutropenia
- Shwachman–Diamond syndrome
- Cartilage–hair hypoplasia
- Dyskeratosis congenita
- Barth syndrome
- Chédiak–Higashi syndrome
- Myelokathexis
- Lazy leukocyte syndrome
- Cohen syndrome
- Hermansky–Pudlak syndrome type 2
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Citation
Schaider, Jeffrey J., et al., editors. "Granulocytopenia." 5-Minute Emergency Consult, 6th ed., Lippincott Williams & Wilkins, 2020. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307332/all/Granulocytopenia.
Granulocytopenia. In: Schaider JJJ, Barkin RMR, Hayden SRS, et al, eds. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307332/all/Granulocytopenia. Accessed October 11, 2024.
Granulocytopenia. (2020). In Schaider, J. J., Barkin, R. M., Hayden, S. R., Wolfe, R. E., Barkin, A. Z., Shayne, P., & Rosen, P. (Eds.), 5-Minute Emergency Consult (6th ed.). Lippincott Williams & Wilkins. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307332/all/Granulocytopenia
Granulocytopenia [Internet]. In: Schaider JJJ, Barkin RMR, Hayden SRS, Wolfe RER, Barkin AZA, Shayne PP, Rosen PP, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. [cited 2024 October 11]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307332/all/Granulocytopenia.
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