Leukocytosis

Leukocytosis is a total white blood cell count above the upper limit of normal, usually over 11 x 10^9/L in adults. It is a laboratory finding that points to infection, inflammation, physiological stress, drugs, or a primary bone marrow disorder, and the cell type that is raised points to the cause.

• Neutrophilia (neutrophils over 7.5 x 10^9/L) is the commonest pattern: bacterial infection, tissue injury, burns, surgery, myocardial infarction, inflammation (vasculitis, gout, inflammatory bowel disease), stress and exercise, pregnancy, smoking, obesity, drugs (corticosteroids, lithium, beta agonists, adrenaline, G-CSF), asplenia, and myeloproliferative neoplasms.
• Lymphocytosis (over 4.0 x 10^9/L): viral infection (EBV, CMV, HIV, hepatitis), pertussis (marked lymphocytosis in children), tuberculosis, brucellosis, toxoplasmosis, chronic lymphocytic leukaemia, and lymphoma.
• Monocytosis (over 1.0 x 10^9/L): tuberculosis, endocarditis, brucellosis, malaria, recovery from neutropenia, chronic myelomonocytic leukaemia, sarcoidosis, and inflammatory bowel disease.
• Eosinophilia and basophilia: allergic disease, parasites, drugs, and myeloproliferative disease.
• Leukaemoid reaction: a count over 50 x 10^9/L from severe infection, tuberculosis, or malignancy that mimics leukaemia, with a left shift but a raised leucocyte alkaline phosphatase score and no blasts.
• A count over 100 x 10^9/L (hyperleukocytosis) is an emergency because of leucostasis in acute leukaemia.

• Often asymptomatic and found on routine FBC.
• Symptoms depend on cause: fever, cough, dysuria, abdominal pain, skin infection, joint pain, weight loss, night sweats, bruising, bone pain, itching after a hot bath, headache, visual disturbance, breathlessness.
• Examination: temperature, focus of infection, lymph nodes, liver and spleen size, bruising, skin rash, joints, signs of dehydration.
• Drug and exposure history: corticosteroids, lithium, smoking, recent surgery or exercise, travel, animal contact, and HIV risk.
• Red flags: count over 50 x 10^9/L, blasts or immature cells on the film, anaemia or thrombocytopenia together, splenomegaly, B symptoms (fever, night sweats, weight loss), neurological or respiratory symptoms with a very high count (leucostasis).

• Repeat FBC with automated differential and review the blood film: toxic granulation, left shift, Dohle bodies (infection); smear cells and mature lymphocytes (chronic lymphocytic leukaemia); atypical lymphocytes (viral); blasts (acute leukaemia); full spectrum of myeloid precursors with basophilia (chronic myeloid leukaemia).
• Initial tests: CRP, ESR, urea and electrolytes, liver function, lactate dehydrogenase, urate, glucose, urinalysis and culture, blood cultures when febrile, chest X-ray, and malaria film in endemic areas.
• Infection specific tests: monospot or EBV serology, HIV test, tuberculosis tests, hepatitis serology, and pertussis PCR in children.
• Haematological tests when persistent, unexplained, or abnormal film: flow cytometry of peripheral blood (lymphocytosis, immunophenotype), BCR-ABL1 PCR (chronic myeloid leukaemia), JAK2 V617F, CALR and MPL mutations (myeloproliferative neoplasms), bone marrow aspirate and trephine.
• Imaging: abdominal ultrasound for spleen and nodes; CT chest, abdomen and pelvis for lymphoma.
• Differentials: reactive leukocytosis, spurious leukocytosis (nucleated red cells, platelet clumping, cryoglobulin, laboratory error), leukaemia, myeloproliferative neoplasm.

Reactive leukocytosis

• Treat the cause and recheck the count: antibiotics for confirmed bacterial infection (choice by site), fluids, analgesia, antipyretics (paracetamol 1 g every 6 hours, maximum 4 g daily), and stop contributory drugs where possible.
• Corticosteroid induced neutrophilia is expected within hours (count may double) and does not need investigation if steroids are the explanation.
• Smoking related and obesity related mild neutrophilia (up to 12 x 10^9/L): advise cessation and weight management; recheck in 4 to 6 weeks.
• Persistent mild leukocytosis (under 15 x 10^9/L) with a normal film, no symptoms and no cause: repeat at 4 to 6 weeks and at 3 months; refer if still raised or rising.

Suspected haematological malignancy

• Refer urgently to haematology (same day if blasts, count over 50 x 10^9/L, cytopenias, or unwell; within 2 weeks for persistent lymphocytosis over 5 x 10^9/L, splenomegaly or lymphadenopathy).
• Chronic lymphocytic leukaemia: observation if early stage and asymptomatic; treatment only for symptoms or progressive disease (specialist).
• Chronic myeloid leukaemia: imatinib 400 mg orally once daily with food (specialist), with monitoring of BCR-ABL1 transcripts.
• Acute leukaemia with hyperleukocytosis: emergency admission, hydration, allopurinol 300 mg daily or rasburicase 0.2 mg/kg for tumour lysis prevention, avoid red cell transfusion where possible, and urgent cytoreduction (hydroxycarbamide 50 to 60 mg/kg/day) before definitive therapy.

Leucostasis and tumour lysis

• Features: confusion, visual change, breathlessness, hypoxia, headache, priapism; this is an emergency needing hydration (2.5 to 3 L/m2/day), allopurinol or rasburicase, leukapheresis in selected cases, and early chemotherapy.

Follow up

• Document the trend; counsel that mild transient rises are common and usually harmless; return urgently for fever, bleeding, night sweats, weight loss, or new lumps.