Urgent considerations
See Differentials for more details
Some serious conditions must be considered when evaluating the aetiology of neutrophilia.
Leukostasis
The degree of leukocytosis should be immediately evaluated, as total leukocyte counts >250×10⁹/L may require immediate leukopheresis to prevent complications to end organs, including respiratory failure, stroke, or myocardial infarction due to occlusion of the pulmonary, intracranial, or coronary circulation, respectively.
The total leukocyte count at which leukostasis develops and requires immediate intervention depends on the type of cell responsible for the elevated count. For example, myeloid blast cells may cause leukostasis at only 50 to 75×10⁹/L, whereas, in chronic lymphocytic leukaemia, the total leukocyte count may exceed 300×10⁹/L without causing symptoms of leukostasis.
Because progression is very rapid, prompt assessment of the patient for end-organ dysfunction is necessary to expedite initiation of leukopheresis and cytotoxic therapy (e.g., hydroxyurea) at the first signs of respiratory, renal, or cardiac compromise.
Haematological malignancies
Specific subtypes of acute myeloid (AML) can present with neutrophilia. The presence of blasts in the peripheral blood should prompt a work-up to exclude acute leukaemia. Over 20% blasts in either the blood or bone marrow is diagnostic of AML. AML is suggested by an elevated total leukocyte count with evidence of immature myeloid cells in the circulation, and associated anaemia and thrombocytopenia. If the diagnosis of AML or lymphoblastic leukaemia (ALL) is being considered, the patient should be urgently referred to a haemato-oncologist.
Any suspected haematological malignancy warrants urgent work-up with FBC, complete metabolic profile, peripheral blood smear, and bone marrow aspiration or core biopsy. Cytogenetic studies may identify the Philadelphia chromosome in cases of chronic myeloid leukaemia or could identify other abnormalities characteristic of myelodysplastic syndrome.
Serious non-malignant diseases
Microangiopathic haemolytic anaemias
These include disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and haemolytic uraemic syndrome (HUS). Diagnosis is suggested by microangiopathic changes to the red blood cells (fragmented red blood cells, reticulocytosis) and enlarged platelets. Half of patients with TTP or HUS have evidence of a neutrophilia or leukocytosis with a total leukocyte count >20×10⁹/L. Some reports suggest neutrophilia is associated with a poor outcome in TTP and HUS.[10]
DIC occurring in the setting of sepsis requires correction of concurrent coagulopathy with blood products such as platelet transfusions, fresh frozen plasma, or cryoprecipitate. Identifying the insult that induced the DIC, such as bacterial pathogens in sepsis, is critical to correcting the condition that results from treatment of the underlying cause. TTP requires urgent evaluation and consideration of therapy with plasma exchange.
Myocardial infarction
Among patients presenting with suspected myocardial infarction, those with a total leukocyte count >9×10⁹/L were 4.5 times more likely to have confirmed myocardial infarction than patients with a total leukocyte count <6×10⁹/L.[20] Leukocytosis is an independent predictor of mortality among patients with acute myocardial infarction.[21][22]
Heat stroke
Morphological changes in circulating neutrophils and elevation of the total neutrophil count occur acutely with heat stroke. Neutrophil segments appear smaller than normal with a botryoid appearance (having numerous rounded protuberances resembling a bunch of grapes).
Infection, systemic inflammatory response syndrome (SIRS), or sepsis
Active infections, not limited to those bacterial in origin, often result in an elevated total leukocyte count with a left shift (an increase in immature granulocytes in the peripheral circulation) among patients of all ages, including preterm infants.[8]
SIRS is defined as the presence of at least 2 of the following criteria: 1) fever >38°C, 2) heart rate >90 bpm, 3) respiratory rate >20 breaths per minute or PaCO₂ <32 mmHg, 4) total WBC count >12×10⁹/L or <4×10⁹/L, or >10% bands (immature neutrophils have a band-shaped nucleus).[2] In the setting of severe sepsis, most commonly in older people and neonates, the total leukocyte and neutrophil counts may be decreased rather than increased.
Although the SIRS criteria have been superseded by the Third International Consensus definitions for sepsis and septic shock (Sepsis-3), they remain in widespread clinical use.[24] The Sepsis-3 criteria include platelet count, but not white blood cell count. For further details on this topic, please see the BMJ Best Practice topic Sepsis in adults.
Particular infectious diseases are associated with more elevated total leukocyte counts, such as those caused by Clostridiumspecies.
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