Low White Blood Cell Count (Leukopenia, Neutropenia): Causes and When It Is Serious

The term leukopenia describes a reduction in the sum of white cells, but in clinical practice one distinguishes which fraction is low. Neutropenia (a low neutrophil count) is the most common cause of leukopenia and the only one that clearly raises the risk of bacterial and fungal infections. Lymphopenia (a low lymphocyte count) can follow an acute infection, stress, drugs (corticosteroids), autoimmune diseases or HIV infection and has different consequences, mainly for cellular immunity. Its discussion goes beyond this article.

These thresholds come from a review for primary care doctors published in American Family Physician, which defines neutropenia as an ANC below 1500 per microlitre in adults and children over one year and divides it into mild (1000–1500), moderate (500–999) and severe (below 500). The 2026 expert guidance additionally notes that the definition depends on ethnic origin and age, and for white adults the World Health Organization adopts a threshold of 1.8 G/L. This detail matters, as we describe below.

As with platelets, a fall in neutrophils results from one of three mechanisms: reduced production in the marrow, accelerated destruction or consumption, or a shift of cells within the body. Reduced production occurs with vitamin and mineral deficiencies (B12, folate, copper), the effect of cytotoxic drugs, marrow involvement by disease (myelodysplastic syndromes, leukaemias, fibrosis) and in rare congenital neutropenias. Accelerated destruction is above all autoimmune neutropenia, drug-induced neutropenia and neutropenia accompanying some viral infections. Consumption concerns severe bacterial infections, in which neutrophils leave the blood in large numbers.

The third mechanism is distribution: some neutrophils circulate in the blood, and some adhere to vessel walls (the marginal pool) or collect in an enlarged spleen (hypersplenism). That is why the count in the blood changes over the day and under the influence of exercise, stress, smoking or corticosteroids, which raise it. There is a practical consequence: a single slightly low result, especially without symptoms, has limited value and is worth repeating.

One of the most important causes of mildly reduced neutrophils, which many people do not know about, is an inherited, harmless reduction in their number, formerly called benign ethnic neutropenia. It is linked to the Duffy-null phenotype, that is, absence of expression of the Duffy antigen (ACKR1) on red blood cells, which is very common in people of African descent and also occurs in other populations of Africa, the Middle East and part of the Mediterranean basin. These people physiologically have a lower neutrophil count, without increased infection risk.

What follows? Above all, that a low neutrophil result in a person of such ancestry, without symptoms and without a history of infections, may be a variant of normal rather than a disease. Laboratories still usually apply one reference range to everyone, which is why the result is flagged as low. Caution is needed, however: this study concerns one clinic in the USA and one group, and ancestry alone does not exclude other causes of neutropenia. The phenotype can be confirmed by genetic testing or Duffy antigen testing, and establishing it can be practically important, for example when qualifying for certain drugs (clozapine) and when assessing results in cancer patients. The decision always rests with the doctor.

In many people low white cells with reduced neutrophils are the result of a recent viral infection. Viruses (influenza, Epstein-Barr virus, cytomegalovirus, measles, rubella, hepatitis viruses, HIV, parvovirus B19 and others) can temporarily suppress neutrophil production in the marrow or speed up their consumption. The fall usually appears in the first days of illness and resolves within roughly a few weeks, and the blood count returns to normal on its own. A single slightly low result just after an infection therefore most often does not need extensive work-up, only repeating after 2–4 weeks.

The exceptions to this rule are cases in which neutropenia persists longer than a few weeks, is deep (below 0.5–1.0 G/L) or is accompanied by other abnormalities. Other causes must then be sought, including HIV or hepatitis virus infection, which may take a chronic course and themselves need to be diagnosed.

Drugs are an important cause of acquired neutropenia. The list is long and includes, among others, chemotherapy drugs, antithyroid drugs (thiamazole and its relatives), clozapine, sulfasalazine, some antibiotics (including trimethoprim with sulfamethoxazole), some anticonvulsants (for example carbamazepine) and metamizole, a popular painkiller and antipyretic in Poland that can in rare cases cause agranulocytosis. The mechanisms vary: a toxic effect on the marrow or an immune reaction in which antibodies destroy neutrophils or their precursors.

Drug-induced agranulocytosis, that is, very deep neutropenia, is rare but potentially dangerous. Typically it reveals itself through fever, sore throat, mouth ulcers or an infection, not through a number on a piece of paper. If such symptoms appear while taking the drugs named, a blood count should be done without delay and a doctor consulted. A drug is stopped only on a doctor's advice, but where agranulocytosis is suspected this is often the first step taken quickly. It is also worth telling the doctor about supplements, because some of them matter in the context of copper (discussed below).

Vitamin B12 or folate deficiency disturbs DNA synthesis in rapidly dividing marrow cells, which can lead to a lower white cell count, together with anaemia and sometimes low platelets. Typically this is accompanied by a raised MCV (large red cells) and the presence of hypersegmented neutrophils on the smear, although not always. The interpretation of B12 and folate tests is described in our entries on vitamin B12 and folic acid, and when macrocytosis points to these deficiencies we discuss in the article on high MCV.

A less well-known cause is copper deficiency, which can cause anaemia, neutropenia (even pancytopenia) and neurological problems similar to B12 deficiency. A review of the literature stresses that copper deficiency is a rare but correctable cause of pancytopenia and is sometimes insufficiently recognised. Risk is raised by bariatric surgery and other gastrointestinal operations, malabsorption syndromes, parenteral nutrition and long-term supplementation with high doses of zinc, which inhibits copper absorption. This matters for people taking high doses of zinc for many months: we discuss the balance of the two minerals in separate entries on zinc. Vitamin deficiencies are relatively easy to detect and treat, so it is worth checking them before looking for more serious causes.

Autoimmune neutropenia may be primary or accompany diseases such as systemic lupus erythematosus or rheumatoid arthritis (including the rare Felty syndrome with an enlarged spleen). Antibodies destroy neutrophils, and the result may vary. In such diseases inflammatory markers are often also raised, for example ESR, which we discuss in a separate entry, although ESR is not specific for leukopenia or for any of these diseases. Diagnosis rests on symptoms, serological tests (antinuclear and other antibodies) and the assessment of a rheumatologist or haematologist.

Marrow diseases such as myelodysplastic syndromes, leukaemias, aplastic anaemia or marrow involvement by cancer are a rarer cause, but they determine vigilance in certain situations. Signals that raise suspicion are: a fall in several blood cell lines at once (anaemia, low platelets and leukopenia together), immature cells (blasts) on the smear, very deep neutropenia without explanation, an enlarged spleen or nodes, weight loss, night sweats and recurrent infections. In that case an assessment by a haematologist is necessary, and often also a bone marrow examination. The 2026 expert guidance on severe chronic neutropenia in adults states that chronic severe neutropenia increases susceptibility to bacterial and fungal infections and that in many patients it is treated with granulocyte colony-stimulating factor (G-CSF).

Infection risk depends on two factors: how low the neutrophils are and how long the state lasts. Classic observations from the 1960s in patients with acute leukaemia showed that the frequency of infections rises as the granulocyte count falls and with the duration of neutropenia, which underlies today's thresholds. In practice this means that an ANC above 1.0 G/L is usually not associated with clearly more infections, between 0.5 and 1.0 G/L the risk is moderate, and below 0.5 G/L, especially if persistent, it clearly increases. These numbers should not be carried from a population of cancer patients to a healthy person with a slightly low result, however, because risk also depends on the cause (constitutional neutropenia or Duffy-null hardly raises it at all).

Fever in a person with severe neutropenia is an emergency. In the American Family Physician review, febrile neutropenia is defined as a single oral temperature of at least 101°F (about 38.3°C) or a temperature of at least 100.4°F (38.0°C) sustained for an hour, with an ANC below 500 per microlitre, and it requires urgent assessment. If you know you have low neutrophils (below 1.0 G/L) and a fever above 38.0°C, chills or feeling unwell appears, do not wait for a follow-up visit; go to a doctor or an emergency department.

This sequence matches the general logic of guidance on neutropenia in adults: first transient and reversible causes (infection, drugs, deficiencies) are excluded, then inherited and autoimmune ones, and last marrow diseases. It is also good to keep a simple diary of results, because the trend over time says more than a single test.

What to do in the meantime? With mild neutropenia without symptoms no special restrictions are needed; ordinary hygiene, hand washing and a quick reaction to fever are enough. Vaccinations and dental treatment are discussed with the doctor. With deeper neutropenia the doctor may recommend additional precautions. Do not stop medicines prescribed for important reasons on your own, or begin 'immunity' supplements in the hope that they will raise neutrophils; there is no reliable evidence that such products increase their number in healthy people.

On the other hand, a single mildly reduced white cell result (3.5–4.0 G/L) in a healthy person, without symptoms, after a recent infection, is usually a reason to repeat the test and not to worry. There is no point booking a haematologist straight away for this result alone, but it should not be ignored if it recurs or falls.

It is also worth remembering that 'high' white cells after corticosteroids, exercise or smoking can mask a low baseline value, and the time of sampling alone changes the result. For comparisons it is therefore better to use results taken in similar conditions.

Low white cells are a result that most often turns out to be mild but must not be automatically dismissed. Three questions are key: what is the absolute neutrophil count, how long has the result been like this, and are there other abnormalities or symptoms. The answers are found in a repeated blood count with differential, a review of medicines and simple tests for deficiencies. If you have a fever with low neutrophils, do not wait; if the result is mild and stable and you feel well, a constitutional variant is very likely. In our series on unusual blood count results we also cover high and low platelets, high eosinophils and high MCV.