July 20, 2007
Causes of Neutrophilia and Treatment
By Auer, Rebecca
Infection is the most common cause of neutrophilia, says Dr Rebecca Auer Neutrophilia is an increase in circulating neutrophils above that expected in a healthy individual of the same age, sex, race and physiological status. TMs represents an increase in the neutrophil count above 7.5 ? 1e'/1 and is one of the most frequently observed changes in the FBC. It is usually due either to a redistribution of white cells or an increase hi bone marrow output.Neutrophilia can occur as a normal physiological process. Healthy neonates have a higher neutrophil count and for infants less than one month old the normal range is as high as 26 xl09/l. Women of childbearuig age have higher neutrophil counts than men, with the count varying during the menstrual cycle.
Pregnancy causes a marked rise in the neutrophil count, which rises even further during and after labour. Vigorous exercise can double the neutrophil count by altering the distribution of white cells within the circulation.
Neutrophilia in pathological conditions is usually due to an increased output from the bone marrow. The major causes of neutrophilia are outlined in the box.
Reactive neutrophilia, where the cause is due to extrinsic factors rather than a primary haemopoietic disorder, is common, with infection being the most common cause.
Most often neutrophilia will be a reactive phenomenon, usually to a bacterial infection where fever as a result of the release of leucocyte pyrogens may also be present.
Neutrophilia itself does not usually cause symptoms and there is no known direct adverse effect until the count is extremely elevated, as seen in myeloproliferative disorders such as chronic myeloid leukaemia.
About 15 per cent of such patients will present with a white blood count above 300 xlO /1 when signs and symptoms of leucostasis develop from impaired microcirculation in the lungs, brain, eyes, ears or penis. Patients may have tachypnoea, dyspnoea, cyanosis, dizziness, slurred speech, delirium, stupor, visual blurring, diplopia, retinal vein distension, retinal haemorrhages, papilloedema, tinnitus, impaired hearing or priapism.
Careful review of the blood film may give clues to the underlying aetiology.
Inflammation of any cause severe enough to cause intensely accelerated neutrophil production will produce changes of cytoplasmic toxic granulation and vacuolation, although the presence of neutrophil vacuolation is more specific for infection, most commonly septicaemia. Dohle bodies basophilic inclusions in the cytoplasm - may also be present.
Other characteristic features of a reactive neutrophilia include a 'shift to the left' in the peripheral blood differential white cell count or an increase in the number of band forms with the occasional presence of cells such as metamyelocytes and myelocytes.
Occasionally this shift is more pronounced with excessive leucocytosis and the appearance of immature myeloblasts, when it is termed a leukaemoid reaction and resembles certain forms of myeloid leukaemia.
Associated disorders include severe or chronic infections, severe haemolysis or metastatic cancer. Leukaemoid reactions are most marked in children. Rouleaux may be present and the platelet count can be elevated during an acute phase response. A normochromic normocytic anaemia may develop and if the inflammatory process is chronic, the red cells may become hypochromic and microcytic.
If neutrophilia is accompanied by myelocytes, promyelocytes and increased basophils in the context of splenomegaly, a primary haematological cause such as a myeloproliferative disorder should be considered.
Specific therapy, if indicated, is generally directed at the underlying cause of neutrophilia. Hyperleucocytosis requires urgent treatment with leucopheresis, hydration and cytoreductive therapy with hydroxyurea.
Referral to a haematologist should be considered where neutrophilia occurs in association with splenomegaly and other abnormalities of the FBC for exclusion of an underlying haematological disorder. Following a review of the blood film, a bone marrow sample will usually be taken to establish the diagnosis.
In patients with a primary haematological diagnosis, such as a myeloproliferative disorder, treatment may involve cytotoxic agents including hydroxyurea to control the blood count. Such therapy requires close specialist supervision with regular blood counts because of the risk of severe life-threatening bone marrow suppression.
In patients with chronic myeloid leukaemia the mainstay of treatment is now imatinib, a tyrosine kinase inhibitor. Again this requires specialist monitoring. Most significantly, imatinib has greatly enhanced survival in this disease.
Causes of neutrophilia
- acute and chronic bacterial infection, especially pyogenic bacteria, either local or generalised, including miliary TB
- some viral infections (eg, chickenpox, herpes simplex)
- some fungal infections
- some parasitic infections (eg, hepatic amoebiasis, Pneumocystiscarinii).
* Inflammation: acute and severe chronic (eg gout, rheumatoid arthritis, ulcerative colitis).
* Tissue damage: eg, trauma, surgery, burns, acute pancreatitis.
* Tissue infarction: feg, Ml, pulmonary embolism causing infarction, sickle cell crisis.
* Acute haemorrhage or haemolysis.
* Acute hypoxia.
* Metabolic and endocrine disorders: eg, diabetic ketoacidosis, acute renal failure, Cushing's syndrome, eclampsia and pre- eclampsia.
* Malignancy: carcinoma, lymphoma, melanoma, sarcoma
* Drugs, especially corticosteroids.
* Myeloproliferative and leukaemic disorders: chronic myeloid leukaemia, myeloproliferative disorders including polycythaemia vera, essential thrombocythaemia, myelofibrosis, chronic myelomonocytic leukaemia, acute myeloid leukaemia (rarely), other rare leukaemias.
* Treatment with myeloid growth factors: cytokines such as granulocyte-colony stimulating factor.
* Post-neutropenia rebound: recovery from cytotoxic chemotherapy, treatment of megaloblastic anaemia.
* Hypersensitivity reactions.
* Inherited causes: deficient surface expression of leucocyte adhesion molecules, hereditary neutrophilia, inherited deficiency of CR3 complement receptors.
"Reactive neutrophilia due to extrinsic factors is common, with infection being the most common cause
Scanning electron microscope image ofShigella bacteria on the surface of a neutrophil. Infection is the most common cause of neutrophilia
"Specific ootherapy, if indicated, is generally directed at the underlying cause of neutophilia
Dr Auer is Leukaemia Research Fund clinician scientist, Barts and The London NHS Trust
Copyright Haymarket Business Publications Ltd. Jul 6, 2007
(c) 2007 GP. Provided by ProQuest Information and Learning. All rights Reserved.