Neutropenia

• Neutropenia is a low number of neutrophils, the white cells that are first to the site of a bacterial infection. It is usually found on a full blood count, often before any symptoms appear.
• It ranges from mild (a small fall) to severe (under 500 cells per microlitre), and the lower the count, the higher the risk of infection. A neutrophil count under 500 with fever is an emergency. ^[1]
• Causes divide into four groups: too few made (chemotherapy, aplastic anaemia, marrow infiltration, vitamin B12 or folate deficiency, congenital disease), too many destroyed (autoimmune disease, drugs such as clozapine, carbamazepine, antithyroid drugs and sulfonamides), a shift into the tissues, and consumption by infection.
• A very common, harmless variant - Duffy-null associated neutrophil count, formerly called benign ethnic neutropenia - lowers the count in people of sub-Saharan African and Middle Eastern ancestry without raising infection risk.
• Febrile neutropenia is treated as an emergency: blood cultures first, then broad-spectrum intravenous antibiotics within the hour, with risk stratification using the MASCC score and, when appropriate, colony-stimulating factor.

By the end of this page you should be able to:

1. Define neutropenia and its severity grades, and calculate the absolute neutrophil count.
2. Classify the causes of neutropenia by mechanism and connect each to a clinical example.
3. Recognise Duffy-null associated neutrophil count and know when not to investigate or treat it.
4. Investigate an unexplained neutropenia with the right first-line and second-line tests and know when to perform bone marrow examination.
5. Manage febrile neutropenia as an emergency, including empiric antibiotics, the MASCC risk index and the use of G-CSF.
6. Explain clozapine-associated neutropenia and its monitoring schedule.

The normal neutrophil count also changes with ancestry. People of sub-Saharan African and Middle Eastern ancestry can have a count genuinely in the range of 500 to 1,500 cells per microlitre and still be healthy, because of the Duffy-null phenotype (see below).^[1] This is not neutropenia in any clinically meaningful sense, and the term "benign ethnic neutropenia" is now discouraged in favour of the genetic name.

Neutropenia is further classified by duration. Acute neutropenia appears over days to weeks; chronic neutropenia persists for more than three months.^[2] Chronic neutropenia is rarely an emergency in itself, but its cause must be established because it may reflect marrow failure, an autoimmune disorder, a drug reaction, or a genetic condition.

The ANC is not read directly from most laboratory reports; it is calculated from the total white cell count and the differential. The standard form is:

ANC (cells per microlitre) = total white cell count (cells per microlitre) multiplied by the percentage of neutrophils plus band forms, divided by 100.

For example, with a white cell count of 4,000 per microlitre and 25 percent neutrophils and bands, the ANC is 4,000 times 25 divided by 100, or 1,000 per microlitre - moderate neutropenia. Only mature granulocytes (bands and segments) count; lymphocytes, metamyelocytes and promyelocytes do not.^[2]

Always confirm the units. A report given as 4.0 times 10 to the 9 per litre is the same as 4,000 per microlitre, and the ANC thresholds below are in the same scale (10 to the 9 per litre equals 1,000 per microlitre). ^[2]

The risk of infection tracks the ANC, which is why grading matters. The European guideline (which uses 1.5 or 1.8 per microlitre as the threshold) and the commonly quoted adult grades are:

The chemotherapy-grading system classifies grade 1 at 1,500 to 2,000, grade 2 at 1,000 to 1,500, grade 3 at 500 to 1,000 and grade 4 at under 500 cells per microlitre.^[3] The two systems overlap; what matters in practice is the actual number and the patient's clinical state, not which label is used.

Acute neutropenia in adults is most often drug-induced or post-infectious and is usually transient. Chronic neutropenia persists for more than three months and includes congenital disease, autoimmune neutropenia, idiopathic (chronic idiopathic neutropenia) and the Duffy-null variant.^[2]

Acquired neutropenia is common in practice but rarely quantified precisely, because most mild cases are asymptomatic and are picked up incidentally. Chemotherapy-induced neutropenia is the most frequent severe form: in solid tumours, the incidence of febrile neutropenia with common myelosuppressive regimens is 13 to 21 percent, and much higher (23 to 36 percent) in the first cycle.^[3] Severe congenital neutropenia and cyclic neutropenia are rare. Duffy-null associated neutropenia is the most common genetic "neutropenia" in the world: the Duffy-null phenotype occurs in 80 to 100 percent of sub-Saharan African populations and 50 to 70 percent of Arab populations, and produces an ANC under 1,500 in many otherwise healthy people.^[2]

The cleanest way to think about causes is by mechanism: production, destruction, redistribution and consumption. The European classification lists the acquired causes in Table 3 of its guideline (infections, autoimmune disease, hypersplenism, drug-induced, nutritional deficiency, haematological disease), and it is worth using that structure when working through a case.^[1]

• Cytotoxic chemotherapy suppresses marrow granulopoiesis. This is the most common cause of severe neutropenia and the one behind almost all febrile neutropenia episodes in cancer care. Risk rises with older age, poor performance status, renal or hepatic impairment, previous neutropenia, metastatic disease and low baseline ANC.^[3]
• Aplastic anaemia is marrow failure with pancytopenia; infection is often the presenting problem.
• Marrow infiltration or replacement - acute leukaemia, myelodysplastic syndromes, lymphoma, metastatic solid tumour, myelofibrosis - crowds out granulopoiesis.
• Nutritional deficiency - vitamin B12, folate, copper, iron or severe protein-calorie malnutrition - impairs DNA synthesis in the marrow.^[1]
• Congenital and genetic disease - severe congenital neutropenia, cyclic neutropenia, Shwachman-Diamond syndrome, Fanconi anaemia, telomere disorders. Most present in childhood but mild forms can be diagnosed in adults.^[1][2]
• Large granular lymphocyte leukaemia and other clonal disorders, which drive T-cell mediated suppression of granulopoiesis.

Autoimmune neutropenia is the commonest immune mechanism: antibodies directed against neutrophil surface antigens, mainly Fc-gamma-RIIIb, accelerate clearance. It is more common in women and in the setting of systemic autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, Felty syndrome).^[2]

Drugs are the most frequent cause of isolated, and sometimes life-threatening, acute neutropenia in adults.^[2] The mechanism may be immune (antibody or T-cell mediated) or direct cytotoxicity to myeloid precursors. Commonly implicated agents include:

• Clozapine and other antipsychotics (olanzapine in some reports).
• Carbamazepine and other anticonvulsants (phenytoin, phenobarbital).
• Antithyroid drugs - propylthiouracil (thiamazole/methimazole) is the classic.
• Sulfonamides and sulfasalazine.
• Antibiotics - beta-lactams, vancomycin, trimethoprim-sulfamethoxazole, fluconazole in some reports.
• Antineoplastic and immunosuppressive agents - rituximab (late-onset neutropenia up to 5 months after infusion), mycophenolate, thiopurines.
• NSAIDs, dipyrone (metamizole), dapsone, penicillamine, ticlopidine, deferiprone and others - many dozens of agents are reported.^[1][2]

Drug-induced neutropenia is usually abrupt and may be severe, but recovery usually occurs within one to three weeks after the drug is stopped. Clozapine warrants its own section below. ^[5]

Neutrophils can be present in adequate (or even increased) numbers in the marrow but low in blood: pseudoneutropenia. This follows a shift of neutrophils into the marginal pool. Causes include overwhelming (Gram-negative) sepsis, anaphylaxis, major surgery, trauma, dialysis and severe viraemia. Hypersplenism, as in portal hypertension or Gaucher disease, sequesters and destroys cells in an enlarged spleen.^[1]

Infection itself consumes neutrophils faster than they can be produced: typhoid fever, malaria, rickettsial disease, tuberculosis, brucellosis, HIV, hepatitis B and C, Epstein-Barr virus, cytomegalovirus and parvovirus B19 are all associated with neutropenia. This pattern is sometimes mistaken for a primary bone marrow disorder; treating the infection and rechecking the count is usually clarifying.^[1]

Neutrophils are the first line of defence against bacteria and fungi: they migrate along chemokine gradients, phagocytose organisms and kill them with oxidative burst and proteases. When the circulating count falls, the host loses the ability to contain organisms at the portal of entry (mucosa, skin, airway), so bacteria and fungi move straight into the bloodstream. The severity of the risk is therefore proportional to the depth and duration of neutropenia, to whether recovery is expected (as after chemotherapy), and to whether functional defects also exist.^[1]

Two further points matter clinically. First, neutropenia blunts inflammation, so a neutropenic patient may have a bacterial pneumonia without sputum, or an intra-abdominal abscess with little or no white cell response; fever may be the only clue. Second, the nadir after myelosuppressive chemotherapy is predictable, so the risk is greatest in that window.^[3]

Uncomplicated, mild neutropenia causes no symptoms at all and is found incidentally. As the count falls, the infections change.

• Recurrent, unusually severe or prolonged infections, often of the mucous membranes and skin: mouth ulcers, gingivitis, periodontitis, tonsillitis, otitis, sinusitis, cellulitis, furuncles, perianal infection.
• Fevers that are out of proportion to the apparent source, or that recur.
• Systemic bacterial infection once the count is severely low: sepsis, pneumonia, neutropenic enterocolitis (typhlitis), perianal sepsis.
• Oral and perirectal lesions are particularly telling in a patient on chemotherapy.

A neutrophil count below 500 with fever or sign of sepsis is treated as neutropenic sepsis whatever the cause.^[4]

This entity used to be called benign ethnic neutropenia, and that name is still widely used. It is now called the Duffy-null associated neutrophil count (DANC), also ACKR1/DARC-associated neutropenia, to emphasise that it is genetic, not cultural.^[1][2]

It results from homozygosity for a single nucleotide polymorphism in the ACKR1 gene, which codes for the Duffy antigen receptor for chemokines on red cells. The mutation (rs2814778) removes Duffy antigen expression on red cells (the Fy(a-b-) phenotype). The proposed mechanism is that the loss of Duffy antigen on red cells, which normally binds inflammatory chemokines, alters neutrophil trafficking between blood and tissues and so lowers the circulating count.^[2]

• In sub-Saharan African populations the Duffy-null phenotype is present in 80 to 100 percent of people; in Arab populations in 50 to 70 percent; in people of European or Asian ancestry it is under 1 percent.^[2]
• It produces an ANC under 1,500 per microlitre, often in the 500 to 1,500 range, in an otherwise healthy person.
• People of African descent have a white cell count about 700 cells per microlitre lower than Caucasian populations on average.^[2]
• The Duffy-null red cell phenotype also offers partial protection against Plasmodium vivax malaria, which is why the allele is so common.^[2]

The essential clinical message: this is not a disease. There is no increased infection risk, no therapy and no further investigation beyond confirming the phenotype (red cell phenotyping for Fy(a-b-), or genotyping for ACKR1 rs2814778). Laboratories and clinicians should use ancestry-aware reference ranges so that a healthy person is not labelled neutropenic, worked up unnecessarily, or denied chemotherapy on the basis of a normal variant.^[2]

A low ANC has three broad origins: it is real and the marrow is not keeping up, it is real but the marrow is normal and the cells are being destroyed or sequestered, or the count is a laboratory artefact (for example an automated analyser misclassifying large granular lymphocytes in T-cell large granular lymphocyte leukaemia). The table below sets out the common possibilities and the feature that separates them.

The work-up depends on whether the neutropenia is acute or chronic and on whether there are red flags. Red flags that move the patient to immediate investigation and often to hospital are: fever, severe neutropenia (under 500), pancytopenia, unexplained weight loss, lymphadenopathy or hepatosplenomegaly, and a falling count over weeks.^[1]

First-line (everyone): full blood count with differential, blood film review, liver and kidney function, vitamin B12 and folate, inflammatory markers, virology (HIV, hepatitis B and C, Epstein-Barr virus, cytomegalovirus, parvovirus B19), thyroid function, autoantibodies (antinuclear antibodies, rheumatoid factor, anti-thyroid antibodies), iron studies, ferritin and immunoglobulins.^[1]

First-line in adults also includes flow cytometry of peripheral blood for large granular lymphocyte clones, antiphospholipid antibodies, antineutrophil antibodies by granulocyte immunofluorescence and erythrocyte sedimentation rate. In children, flow cytometry for T-cell receptor alpha-beta double-negative lymphocytes is added.^[1]

Second-line, when the first is unrevealing: serial blood counts (twice weekly for six weeks to exclude cyclic neutropenia), copper and ceruloplasmin, anti-tissue transglutaminase antibodies, pancreatic isoamylase, serum electrophoresis, complement levels, and genetic testing. In an asymptomatic person of African or Middle Eastern descent, red cell phenotyping for Fy(a-b-) is the correct first test and makes the diagnosis without any further work-up.^[1][2]

Bone marrow examination is recommended for adults with unexplained chronic neutropenia, for anyone before G-CSF treatment, for patients with suspected autoimmune neutropenia but negative antibody tests and recurrent infections, and for anyone with additional cytopenias or a falling count. It may be omitted in long-standing, mild, stable neutropenia with a normal first-line screen.^[1]

The diagnosis of neutropenia itself is numerical, set out in the Severity grades table above. Two clinical scoring systems drive management decisions.

Febrile neutropenia is defined as a fever of 38.3 degrees Celsius or higher once, or 38.0 degrees or higher for more than one hour, with an absolute neutrophil count under 500 per microlitre, or under 1,000 with an expected fall below 500 within 48 hours.^[3] Neutropenic sepsis (the UK term) is confirmed when the count is 0.5 times 10 to the 9 per litre or lower with fever above 38 degrees Celsius or other signs of sepsis.^[4]

For risk stratification, the Multinational Association for Supportive Care in Cancer (MASCC) risk index is the classic score. It has 7 items with a maximum of 26 points; a score of 21 or more predicts a low risk of complications and a score below 21 a high risk. Its items are burden of illness (no or mild symptoms 5 points, moderate 3), absence of hypotension (5), absence of chronic obstructive pulmonary disease (4), solid tumour or controlled haematological malignancy (4), absence of dehydration (3), outpatient status at onset (3) and age under 60 (2).^[3] ASCO (American Society of Clinical Oncology) and IDSA (Infectious Diseases Society of America) guidance is usually delivered as risk-stratified management of fever and neutropenia, and the same practical steps appear in the NICE guideline summarised below: assess risk, give empiric antibiotics, and reconsider at 48 hours.^[4]

NICE specifies management by risk: risk scoring within 24 hours using a validated score (MASCC or, for children, the Modified Alexander rule), outpatient antibiotic therapy considered for low-risk patients, daily reassessment for high-risk patients, switch from intravenous to oral antibiotics after 48 hours once risk is reassessed as low, and discontinuation of empiric antibiotics once the episode has responded regardless of neutrophil count.^[4]

Febrile neutropenia is an oncological emergency. Guidelines are unanimous that empiric broad-spectrum intravenous antibiotics should be given as soon as possible, and the British guideline specifies immediately, ideally within one hour of recognising the fever.^[4] The first steps are:

1. Rapid assessment: history, examination, temperature, heart rate, blood pressure, oxygen saturation.
2. Blood cultures: at least one set from a peripheral vein, plus a set from any central venous access device if present.^[4]
3. Full blood count, renal and liver function, C-reactive protein, lactate. A chest X-ray only if clinically indicated.^[4]
4. Urinalysis in children under 5.^[4]
5. Empiric intravenous antibiotics without waiting for results.

Initial investigation also includes looking for a source (mouth and perianal examination, abdominal and chest examination), but do not let this delay antibiotics. Do not remove central venous lines as part of first management.^[4]

The choice follows local ecology and guidelines; the key principle, shared by IDSA, ASCO and NICE, is to cover Pseudomonas aeruginosa and other serious Gram-negative pathogens from the first dose.^[3][4]

• First-line (NICE and Ba et al.): antipseudomonal beta-lactam monotherapy. Piperacillin with tazobactam is the standard (3.375 g intravenously every 6 hours for mild to moderate, or 4.5 g every 6 to 8 hours for severe infection). Cefepime (2 g intravenously every 8 hours), imipenem (500 mg every 6 hours) and meropenem (1 to 2 g every 8 hours) are alternatives.^[3][4]
• Do not use an aminoglycoside as monotherapy or in dual therapy for initial empiric treatment unless there are specific microbiological indications, and do not add an empiric glycopeptide for a central venous line unless there are patient-specific or local reasons.^[4]
• Low-risk (MASCC 21 or higher) patients can be considered for oral empiric therapy after assessment by a specialist, for example a fluoroquinolone (moxifloxacin 400 mg daily or levofloxacin 500 to 750 mg daily) with or without amoxicillin-clavulanate, and even outpatient management in selected circumstances.^[3][4]
• High-risk patients (MASCC under 21) are admitted, rechecked daily with a validated score, and treated intravenously. Switch from intravenous to oral therapy once the risk is reassessed as low, and stop empiric antibiotics once the episode has responded, irrespective of the neutrophil count.^[4]
• Persisting fever after 72 to 96 hours of antibiotics should prompt a CT scan of the chest, consideration of invasive fungal infection, and empirical antifungal therapy such as caspofungin (70 mg intravenously once, then 50 mg daily) or liposomal amphotericin B (3 to 5 mg per kg daily).^[3]

Therapeutic (not prophylactic) G-CSF shortens the neutrophil recovery and hospital stay, but its effect on overall and infection-related mortality is not proven. Guidelines therefore reserve therapeutic G-CSF for febrile neutropenia with risk factors for poor outcome: age over 65, sepsis syndrome, ANC under 100 per microlitre, expected neutropenia over 10 days, pneumonia, invasive fungal infection, documented infection, low MASCC score (under 21), low platelet count (under 50,000), hypoproteinemia.^[1][3] A daily rise in neutrophils is usually seen within 24 to 48 hours of starting G-CSF.^[2]

If the patient was already on short-acting prophylactic G-CSF, continue it; if on long-acting (pegylated) G-CSF, do not add short-acting G-CSF; if on none, decide on the risk factors above.^[3]

For patients about to start chemotherapy, prophylactic G-CSF is recommended when the chance of febrile neutropenia is 20 percent or higher, considered at 10 to 20 percent in patients with additional risk factors, and generally not used under 10 percent.^[3] Antibiotic prophylaxis (fluoroquinolone, usually ciprofloxacin) during the expected neutropenic period is recommended for high-risk groups such as acute leukaemias and stem cell transplant recipients, with resistance monitoring in the unit; routine G-CSF is not recommended solely to prevent neutropenic sepsis in adults unless it is part of the chemotherapy plan or needed to maintain dose intensity.^[4]

Treatment is individualised: the goal is to avoid infection rather than normalise a number. Individuals with Duffy-null associated neutrophil count need nothing. Chronic idiopathic and autoimmune neutropenia with few infections are observed. G-CSF is used when there is a clinically important infection burden: usually the lowest effective dose, with an ANC of 1.0 times 10 to the 9 per litre or higher generally accepted as protective.^[2]

Typical regimens, from the 2025 review and the 2023 European guideline:

• Severe congenital neutropenia: start 5 micrograms per kg per day subcutaneously, escalate by 1 to 2 micrograms per kg per week to reach and maintain an ANC of 1.0 to 5.0 times 10 to the 9 per litre.^[1][2]
• Chronic idiopathic and autoimmune neutropenia: 1 to 5 micrograms per kg per day two to three times weekly (median 1.2 micrograms per kg per day) on an on-demand basis.^[2]
• Cyclic neutropenia: median about 2.5 micrograms per kg per day.^[2]
• Prophylactic antibiotics are not recommended as routine in chronic neutropenia.^[2]

G-CSF increases neutrophils within 24 to 48 hours. Side effects include bone pain, myalgia, headache, splenomegaly, thrombocytopenia and reduced bone density; it has not been shown to cause short-term harm in pregnancy and appears safe.^[2] High-dose, long-term G-CSF in congenital neutropenia carries a risk of progression to myelodysplastic syndrome and acute myeloid leukaemia, mainly through CSF3R and RUNX1 mutation, so these patients need follow-up marrow surveillance.^[1]

Clozapine carries a well-quantified risk of neutropenia and agranulocytosis: about 0.7 to 0.8 percent over a year, with 84 percent of agranulocytosis cases occurring in the first three months and 96 percent within six months of starting treatment. Only a quarter of patients with mild neutropenia progress to severe neutropenia, and about 2 percent of agranulocytosis cases are fatal. The incidence may be lower in non-schizophrenic indications; in Parkinson disease psychosis the medium-term incidence is roughly 0.1 percent.^[5]

For these reasons the traditional monitoring schedule is weighted to the first months: full blood count and absolute neutrophil count weekly for the first 6 months, every 2 weeks from 6 to 12 months, and monthly thereafter, though the exact obligation now varies by country and the FDA lifted the REMS requirement in 2025 while the label text still reflects the old schedule. Recovery of the neutrophil count after clozapine-induced agranulocytosis takes one to three weeks, and clozapine must be stopped at once if severe neutropenia is confirmed. Many other drugs cause neutropenia (anticonvulsants such as carbamazepine, phenytoin and phenobarbital, antithyroid drugs, sulfonamides, sulfasalazine, ticlopidine, deferiprone, thioamides and rituximab), so a review of all medication is essential before attributing neutropenia to clozapine.^[5]

Rechallenge after a clozapine-associated neutropenia has been described with close monitoring and a favourable risk-benefit analysis, but this is specialist practice.^[1][2]

• Bacterial and fungal sepsis, the dominant cause of harm in severe neutropenia.
• Pneumonia, including atypical and invasive fungal forms.
• Neutropenic enterocolitis (typhlitis) and perianal sepsis.
• Mucositis and neutropenic colitis in chemotherapy patients.
• In drug-induced neutropenia, delayed recovery can allow invasive fungal infection.
• In severe congenital neutropenia, leukemic transformation driven by CSF3R and RUNX1 mutation after long-term G-CSF.
• Over-investigation and withholding of cancer treatment when Duffy-null associated neutrophil count is mistaken for disease.

Prognosis depends entirely on the cause. Duffy-null associated neutrophil count and the mild chronic idiopathic forms have an essentially normal lifespan and (for the latter, unless severe) a low infection burden. Chemotherapy-induced neutropenia is nowadays usually recoverable and its mortality has fallen with prompt empiric antibiotics and growth factor support. Severe congenital neutropenia, before G-CSF, was life-limiting from infection; with modern therapy most patients reach adulthood, at the cost of long-term marrow surveillance. Agranulocytosis from drugs (for example carbamazepine or antithyroid drugs) has a mortality of a few percent, mostly from sepsis.^[5] The duration of neutropenia, not just its depth, is what separates a recoverable dip from a dangerous one.^[3]

• Anticipate neutropenia before chemotherapy by checking baseline counts and planning growth factor support according to the regimen's febrile neutropenia risk.^[3]
• Prompt recognition and treatment of febrile neutropenia; patient education and a 24-hour access card are core to the NICE guideline.^[4]
• For clozapine, the monitoring schedule above.^[5]
• Ancestry-aware reference ranges prevent misdiagnosis in Duffy-null associated neutrophil count.^[2]
• Vaccination: routine vaccines are indicated in chronic neutropenia without additional immune defect, according to national schedules; live vaccines only when clinically appropriate.^[2]

• Pregnancy. G-CSF has been used in pregnancy in chronic neutropenia with apparent safety and efficacy, but decisions should be specialist; treat febrile neutropenia in a pregnant patient as for any cancer patient, with obstetric and haematology input.^[2]
• Children. Most congenital causes present in infancy. Modified Alexander rule is used for children with febrile neutropenia. Severe congenital neutropenia needs genetic work-up and life-long G-CSF.^[1][4]
• Older adults. Age over 65 is an independent risk factor both for febrile neutropenia and for poor outcome, and the same drugs (clozapine among them) behave less predictably.^[3][5]
• Immunocompromised hosts (HIV, transplants, biologic therapy). Antiretroviral therapy itself can cause neutropenia; the threshold for investigation and treatment is lower.

• The diagnosis of a dangerous neutropenia requires only a full blood count with differential: a Coulter counter is ideal, but a manual white cell count and a differential stain can be done anywhere and will separate neutrophil from lymphocyte depletion.
• Empiric antibiotics for suspected febrile neutropenia should be given whenever they are available; ceftriaxone or an antipseudomonal penicillin is preferable where obtainable, but the exact regimen should follow what the local microbiology service can support.
• Where G-CSF is unavailable, supportive care (hydration, source control, and the empiric antibiotic above) is the mainstay; on-demand G-CSF can be rationed to severe congenital or recurrent cases.
• In communities with high Duffy-null prevalence, ancestry-aware reference ranges prevent over-investigation and the inappropriate withholding of chemotherapy; a simple red cell phenotype (Fy(a-b-)) costs far less than a marrow examination.
• When microbiology is absent, take blood cultures before antibiotics if they can be processed, and treat suspected neutropenic sepsis regardless.

• Neutropenia is a low absolute neutrophil count; commonly graded mild at 1,000 to 1,500, moderate at 500 to 999, severe under 500 and agranulocytosis under 200 cells per microlitre.^{[1] [5]}
• The ANC is calculated from the total white cell count and the neutrophil percentage.
• Causes are reduced production, increased destruction, redistribution and infection; drugs are the commonest acute cause.
• Duffy-null associated neutrophil count is a harmless, genetic variant in people of African and Middle Eastern ancestry; it needs no treatment.
• Febrile neutropenia is an emergency: blood cultures then broad-spectrum intravenous antibiotics as soon as possible, ideally within the hour.^[4]
• The MASCC risk index (maximum 26, 21 or more predicts low risk) stratifies patients for oral or outpatient therapy.^[3]
• Chemotherapy prophylaxis with G-CSF is recommended at 20 percent or higher risk of febrile neutropenia and considered at 10 to 20 percent.^[3]
• Chronic neutropenia is treated according to the infection burden, usually with on-demand G-CSF at 1 to 5 micrograms per kg two to three times weekly.^[2]
• Clozapine carries a 0.7 to 0.8 percent agranulocytosis risk concentrated in the first 3 to 6 months, requiring frequent blood count monitoring.^[5]
• Empiric antibiotics are started without waiting for culture results but are stopped once the episode has responded.^[4]

Aplastic anaemia, autoimmune neutropenia, drug-induced neutropenia, cyclic neutropenia, severe congenital neutropenia, febrile neutropenia, myelodysplastic syndromes, G-CSF therapy, agranulocytosis, bone marrow failure.