Diagnostic Considerations

Conditions to be considered include the following:

Large granular lymphocyte leukemia
Autoimmune diseases
Chronic myelomonocytic leukemia
Congenital neutropenia
Cyclic neutropenia
Drug-induced neutropenia
Large granular lymphocytic leukemia
Pseudoneutropenia

Obtain a detailed history in patients with neutropenia or agranulocytosis, with particular emphasis on medication use. The inquiry must extend back in time to include discontinued medications. Over-the-counter drugs must be included in the inquiry because patients often do not consider these agents to be medications. Any possible occupational or accidental exposure to toxic chemicals or physical agents must be excluded. Agranulocytosis should be differentiated from other syndromes of bone marrow failure, including pancytopenia and aplastic anemia. Leukemia should be excluded.

Differential Diagnoses

Workup

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Media Gallery

The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Doppler sonogram at the splenic hilum reveals hepatofugal venous flow in a patient with portal hypertension.
Two neutrophils among red blood cells. Courtesy of Britannica (https://www.britannica.com/science/neutrophil).

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Table 1. Genetic (Hereditary) Conditions in Neutropenia

Table 1. Genetic (Hereditary) Conditions in Neutropenia

Syndrome	Inheritance	Gene	Clinical Features
Cyclic neutropenia	Autosomal dominant	ELA2	Alternate 21-day cycling of neutrophils and monocytes
Kostmann syndrome	Autosomal recessive	Unknown	Stable neutropenia, no MDS or AML
Severe congenital neutropenia	Autosomal dominant	ELA2 (35-84%)	Stable neutropenia, MDS or AML
	Autosomal dominant	GFI1	Stable neutropenia, circulating myeloid progenitors, lymphopenia
	Sex linked	Wasp	Neutropenic variant of Wiskott-Aldrich syndrome
	Autosomal dominant	G-CSFR	G-CSF–refractory neutropenia, no AML or MDS
Hermansky-Pudlak syndrome type 2	Autosomal recessive	AP3B1	Severe congenital neutropenia, platelet dense-body defect, oculocutaneous albinism
Chediak-Higashi syndrome	Autosomal recessive	LYST	Neutropenia, oculocutaneous albinism, giant lysosomes, impaired platelet function
Barth syndrome	Sex linked	TAZ	Neutropenia, often cyclic; cardiomyopathy, methylglutaconic aciduria
Cohen syndrome	Autosomal recessive	COH1	Neutropenia, mental retardation, dysmorphism
Thrombocytopenia with absent radii (TAR)	Autosomal recessive	RBM8A	Thrombocytopenia, MDS, absent radii, abnormal ulna
Diamond-Blackfan anemia	Autosomal dominant, X-linked recessive	RPS19, RPL5, RPS26	Macrocytic anemia, other cytopenias, solid tumors, short stature, abnormal thumbs, cardiac septal defect
Fanconi syndrome	Autosomal recessive (rarely, X-linked recessive or autosomal dominant)	FANCA, FANCC, FANCG	Pancytopenia, solid tumors, skin hyperpigmentation and café au lait spots, abnormal thumbs
Dyskeratosis congenita	X-linked recessive, autosomal dominant, autosomal recessive	DKC1, TINF2	Pancytopenia, MDS, nail dystrophy, leukoplakia, solid tumors
Source: Modified from Berliner et al, 2004.^[23] AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome.

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Author

Carly DeFaria, MD Resident Physician, Department of Internal Medicine, Einstein Medical Center

Carly DeFaria, MD is a member of the following medical societies: American College of Physicians, American Medical Student Association/Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee

Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

Ariel Distenfeld, MD Clinical Professor, Department of Medicine, New York University School of Medicine

Disclosure: Nothing to disclose.

John E Godwin, MD, MS Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.