Neutropenia

Neutropenia
Blood film with a striking absence of neutrophils, leaving only red blood cells and platelets
Classification and external resources
Specialty	Infectious disease
ICD-10	D70
ICD-9-CM	288.0
DiseasesDB	8994
eMedicine	med/1640
MeSH	D009503

Neutropenia or neutropaenia, from Latin prefix neutro- ("neither", for neutral staining) and Greek suffix -πενία (-penía, "deficiency"), is a granulocyte disorder characterized by an abnormally low number of neutrophils. Neutrophils usually make up 60 to 70% of circulating white blood cells and serve as the primary defense against infections by destroying bacteria in the blood. Hence, patients with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening and deadly (neutropenic sepsis).

Neutropenia can be acute or chronic depending on the duration of the illness. A patient has chronic neutropenia if the condition lasts longer than three months. It is sometimes used interchangeably with the term leukopenia ("deficit in the number of white blood cells"), as neutrophils are the most abundant leukocytes, but neutropenia is more properly considered a subset of leukopenia as a whole.

The numerous causes of neutropenia can roughly be divided between problems in the production of the cells by the bone marrow and destruction of the cells elsewhere in the body. Treatment depends on the nature of the cause, and emphasis is placed on the prevention and treatment of infection.

Signs and symptoms

Neutropenia can go undetected, but is generally discovered when a patient has developed severe infections or sepsis. Some common infections can take an unexpected course in neutropenic patients; formation of pus, for example, can be notably absent, as this requires circulating neutrophil granulocytes.

Some common symptoms of neutropenia include fevers and frequent infections. These infections can result in conditions such as mouth ulcers, diarrhea, a burning sensation when urinating, unusual redness, pain or swelling around a wound, or a sore throat.

Causes

Causes can be divided into these groups:

• Decreased production in the bone marrow due to:
  • aplastic anemia
  • arsenic poisoning
  • cancer, particularly blood cancers
  • hereditary disorders (e.g. congenital neutropenia, cyclic neutropenia)
  • radiation
  • Vitamin B₁₂, folate or copper deficiency
• Increased destruction:
  • autoimmune neutropenia
  • chemotherapy treatments, such as for cancer and autoimmune diseases
• Marginalisation and sequestration:
  • Hemodialysis
• Medications
  • Flecainide (a class 1C cardiac antiarrhythmic drug)
  • Phenytoin
  • Indomethacin
  • Propylthiouracil
  • Carbimazole
  • Chlorpromazine
  • Trimethoprim/sulfamethoxazole (cotrimoxazole)
  • Clozapine
  • Ticlopidine

Often, a mild neutropenia is seen in viral infections. Additionally, a condition called morning pseudoneutropenia might be a side effect of certain antipsychotic medications.

Diagnosis

Low neutrophil counts are detected on a full blood count. Generally, other investigations are required to arrive at the right diagnosis. When the diagnosis is uncertain, or serious causes are suspected, bone marrow biopsy is often necessary.

Other investigations commonly performed: serial neutrophil counts for suspected cyclic neutropenia, tests for antineutrophil antibodies, autoantibody screen and investigations for systemic lupus erythematosus, vitamin B₁₂ and folate assays, and acidified serum (Ham's) test.

Classification

A generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl):

• Mild neutropenia (1000 ≥ ANC < 1500) — minimal risk of infection
• Moderate neutropenia (500 ≥ ANC < 1000) — moderate risk of infection
• Severe neutropenia (ANC < 500) — severe risk of infection.

Each of these are either derived from laboratory tests or via the formula below:

ANC = $(\%neutrophils + \%bands)\times (WBC)\over (100)$

The Clinical Index of Stable Febrile Neutropenia (CISNE) can also be used to stratify the risk of serious complications

Treatment

No ideal therapy for neutropenia exists, but recombinant granulocyte-colony stimulating factor, such as filgrastim (Neupogen) and [filgrastim-sndz] (Zarxio), can be effective in chemotherapy patients, in patients with congenital forms of neutropenia including severe congenital neutropenia, autosomal recessive Kostmann's syndrome, cyclic neutropenia, and myelokathexis.

Guidelines for neutropenia regarding diet are currently being studied.

Amifostine is used for neutropenic infection associated with cisplatin and cyclophophamide.

History

The relationship between a low neutrophil count and increased risk of infection was first demonstrated in patients with leukemia.

See also

• Pancytopenia
• Thrombocytopenia

External links

• National Neutropenia Network
• Severe Chronic Neutropenia International Registry
• ANC calculation