Full Blood Count

The full blood count is an automated analysis of EDTA-anticoagulated whole blood that reports red cell, leucocyte and platelet numbers together with red cell indices. Cells are counted and sized by impedance, optical scatter and fluorescence flow cytometry, and haemoglobin is measured spectrophotometrically after lysis. It identifies anaemia, polycythaemia, cytopenias and leucocyte abnormalities, and determines which test follows.

It is the most frequently requested haematology test. Abnormal results are common in hospital populations, most often anaemia.

Indications. Fatigue, pallor, dyspnoea, bleeding or bruising, fever, recurrent infection, splenomegaly, lymphadenopathy, bone pain; monitoring of chemotherapy, clozapine, carbamazepine, methotrexate, azathioprine, linezolid and heparin; preoperative assessment; antenatal screening.

Specimen. Venous or capillary EDTA blood, analysed within 6 hours for best platelet and differential accuracy and within 24 hours for most counts. MCV and haematocrit drift upwards with storage.

Adult reference ranges are given. Local laboratory ranges take precedence.

Haemoglobin. Oxygen carrying protein concentration and the defining measure of anaemia. Range: men 135 to 175 g/L (13.5 to 17.5 g/dL), women 120 to 155 g/L (12.0 to 15.5 g/dL). Raised: polycythaemia vera, chronic hypoxia (lung disease, sleep apnoea, high altitude), smoking, erythropoietin secreting tumours, testosterone therapy, dehydration. Lowered: anaemia from any cause, haemodilution (pregnancy, intravenous fluids, paraproteinaemia).

Anaemia is usually defined as under 130 g/L in men and under 120 g/L in non-pregnant women. A fall of over 20 g/L over a short period indicates bleeding or haemolysis. Acute haemorrhage does not lower haemoglobin until haemodilution has occurred.

Haematocrit. Fraction of blood volume occupied by red cells, calculated as MCV multiplied by red cell count. Range: men 0.40 to 0.52 L/L, women 0.36 to 0.46 L/L. Raised and lowered: mirrors haemoglobin.

Suspected polycythaemia vera is flagged by haemoglobin over 165 g/L or haematocrit over 0.49 in men, and haemoglobin over 160 g/L or haematocrit over 0.48 in women. Values over 0.60 carry a marked thrombotic and hyperviscosity risk.

Red cell count. Number of red cells in a litre of blood. Range: men 4.5 to 6.0 x10¹²/L, women 3.8 to 5.2 x10¹²/L. Raised: polycythaemia, thalassaemia trait, dehydration. Lowered: anaemia.

A high count with a low MCV and mild or no anaemia favours thalassaemia trait. The Mentzer index (MCV divided by red cell count) under 13 favours thalassaemia trait and over 13 favours iron deficiency, with limited accuracy.

Mean cell volume (MCV). Average red cell size and the principal tool for classifying anaemia. Range: 80 to 100 fL. Raised: vitamin B12 or folate deficiency, alcohol, liver disease, hypothyroidism, myelodysplasia, hydroxycarbamide, methotrexate, azathioprine, zidovudine, valproate, reticulocytosis, newborns (physiologically 95 to 120 fL), and spuriously with cold agglutinins or marked hyperglycaemia. Lowered: iron deficiency, thalassaemia, sideroblastic anaemia, lead poisoning, haemoglobin E, mild anaemia of chronic disease.

Mixed deficiencies produce a normal MCV with a raised RDW. A raised MCV with a normal haemoglobin is still significant and needs a cause.

Mean cell haemoglobin (MCH). Average haemoglobin mass in each red cell. Range: 27 to 32 pg. Raised: macrocytosis. Lowered: hypochromia from iron deficiency or thalassaemia.

It tracks MCV and is less affected by storage artefact than MCHC.

Mean cell haemoglobin concentration (MCHC). Average haemoglobin concentration within red cells. Range: 320 to 360 g/L (32 to 36 g/dL). Raised: hereditary spherocytosis, haemoglobin C disease, and spuriously with cold agglutinins, lipaemia or severe hyperbilirubinaemia. Lowered: iron deficiency, thalassaemia.

A value over 360 g/L is rarely physiological, so check for artefact and look for spherocytes on the film.

Red cell distribution width (RDW). Coefficient of variation of red cell size, a measure of anisocytosis. Range: 11.5 to 14.5%. Raised: early iron deficiency, mixed deficiency, megaloblastic anaemia, haemolysis with reticulocytosis, recent transfusion, myelodysplasia, sickle cell disease. Lowered: no clinical significance.

A raised RDW with a normal MCV is an early marker of iron deficiency or mixed deficiency. A normal RDW with microcytosis favours thalassaemia trait.

Total leucocyte count. Sum of all circulating white cells. Range: 4.0 to 11.0 x10⁹/L. Raised: bacterial infection, inflammation, corticosteroids, physical or emotional stress, smoking, pregnancy, leukaemia, myeloproliferative neoplasms. Lowered: viral infection, sepsis, marrow failure, hypersplenism, vitamin B12 or folate deficiency, drugs, autoimmune disease.

An unexplained count over 30 x10⁹/L needs film review. Counts over 100 x10⁹/L in acute leukaemia carry a risk of leucostasis.

Neutrophils. Primary phagocytic defence against bacteria and fungi. Range: 2.0 to 7.5 x10⁹/L. Raised: bacterial infection, corticosteroids, stress, smoking, myeloproliferative neoplasms, tissue necrosis. Lowered: chemotherapy, drugs (clozapine, carbimazole, sulphasalazine, other antithyroid drugs), viral infection, autoimmune neutropenia, marrow failure, B12 or folate deficiency.

Neutropenia is mild at 1.0 to 1.5, moderate at 0.5 to 1.0 and severe under 0.5 x10⁹/L. In people of African, Middle Eastern and some other ancestries, benign ethnic neutropenia (Duffy null associated) gives counts of 1.0 to 1.5 x10⁹/L without added infection risk.

Lymphocytes. Mediators of adaptive immunity. Range: 1.0 to 4.0 x10⁹/L. Raised: viral infection (EBV, CMV), pertussis, chronic lymphocytic leukaemia, lymphoma, infancy and early childhood (normally higher). Lowered: HIV, corticosteroids, chemotherapy, lupus, severe illness.

Persistent lymphocytosis over 5 x10⁹/L in an older adult suggests clonal B-cell disease and needs flow cytometry.

Monocytes. Range: 0.2 to 1.0 x10⁹/L. Raised: chronic infection (tuberculosis, endocarditis), recovery from neutropenia, inflammatory bowel disease, sarcoidosis, chronic myelomonocytic leukaemia. Lowered: hairy cell leukaemia, aplastic anaemia, corticosteroids.

Persistent monocytosis over 1.0 x10⁹/L with monocytes over 10% of leucocytes raises the possibility of chronic myelomonocytic leukaemia.

Eosinophils. Range: 0.04 to 0.4 x10⁹/L. Raised: atopy, drug reactions including DRESS, tissue invasive helminths (strongyloidiasis, schistosomiasis, filariasis), eosinophilic granulomatosis with polyangiitis, adrenal insufficiency, Hodgkin lymphoma, hypereosinophilic syndromes. Lowered: acute stress, corticosteroids, Cushing syndrome.

Persistent counts over 1.5 x10⁹/L need assessment for organ damage, including troponin and echocardiography.

Basophils. Range: 0.0 to 0.1 x10⁹/L. Raised: chronic myeloid leukaemia, other myeloproliferative neoplasms, hypothyroidism, allergic states. Lowered: not interpretable.

Basophilia with leucocytosis and a left shift suggests chronic myeloid leukaemia.

Platelets. Range: 150 to 400 x10⁹/L. Raised: reactive (iron deficiency, infection, inflammation, post-splenectomy, malignancy, tissue injury), essential thrombocythaemia, polycythaemia vera, chronic myeloid leukaemia, myelofibrosis. Lowered: immune thrombocytopenia, drugs, heparin induced thrombocytopenia (typically 5 to 14 days after heparin starts), DIC, thrombotic microangiopathy, HELLP syndrome, hypersplenism, marrow failure, B12 or folate deficiency, viral infection, alcohol, pseudothrombocytopenia.

Spontaneous bleeding risk rises under 20 x10⁹/L, and surgical bleeding risk rises under 50 x10⁹/L. Counts over 1000 x10⁹/L can cause acquired von Willebrand syndrome.

Mean platelet volume (MPV). Range: 7.5 to 11.5 fL. Raised: immune thrombocytopenia, myeloproliferative neoplasms, Bernard-Soulier syndrome. Lowered: marrow failure, Wiskott-Aldrich syndrome.

A raised MPV in thrombocytopenia favours peripheral destruction, and a low MPV favours underproduction.

Anaemia by MCV.

• Microcytic (under 80 fL): iron deficiency, thalassaemia trait, anaemia of chronic disease, sideroblastic anaemia.
• Normocytic (80 to 100 fL): acute blood loss, anaemia of chronic disease, chronic kidney disease, haemolysis, marrow failure, early or mixed deficiency, endocrine disease.
• Macrocytic (over 100 fL): megaloblastic anaemia, alcohol, liver disease, hypothyroidism, myelodysplasia, drugs, reticulocytosis.

Pancytopenia. Aplastic anaemia, myelodysplasia, acute leukaemia, megaloblastic anaemia, marrow infiltration, hypersplenism, paroxysmal nocturnal haemoglobinuria, HIV, lupus, overwhelming sepsis, drugs.

Polycythaemia. Polycythaemia vera with a low erythropoietin level, secondary causes (hypoxia, erythropoietin producing tumours, androgens, post-transplant erythrocytosis) and relative polycythaemia from plasma volume loss.

Critical values and findings needing immediate action.

• Haemoglobin under 70 g/L or over 200 g/L.
• Neutrophils under 0.5 x10⁹/L, particularly with fever.
• Platelets under 20 x10⁹/L, or any thrombocytopenia with schistocytes and neurological or renal features.
• Total leucocyte count over 30 x10⁹/L with blasts, or over 100 x10⁹/L.
• New onset pancytopenia.

Interferences and artefacts.

• EDTA-dependent platelet clumping causes pseudothrombocytopenia. Repeat in citrate or heparin and check the film.
• Cold agglutinins raise MCV and MCHC and lower the red cell count. Warm the sample to 37 °C.
• Lipaemia, hyperbilirubinaemia and very high white counts falsely raise haemoglobin.
• Nucleated red cells and giant platelets can be counted as leucocytes or red cells.
• A sample drawn from the arm receiving an infusion is diluted.
• Samples older than 24 hours show artefactual MCV and differential changes.

Special groups.

• Neonates: haemoglobin about 140 to 220 g/L at birth, with a physiological nadir at 6 to 8 weeks. Lymphocytes dominate in infants.
• Pregnancy: haemodilution lowers haemoglobin. Anaemia is defined as under 110 g/L in the first and third trimesters and under 105 g/L in the second. Platelets fall modestly, and gestational thrombocytopenia can occur.
• Older adults: mild anaemia should not be assumed to be physiological, and a cause is usually found.
• Altitude and smoking raise haemoglobin.

Follow up tests. Reticulocyte count, blood film, ferritin and iron studies, vitamin B12 and folate, haemolysis screen, direct antiglobulin test, haemoglobin electrophoresis, erythropoietin level, flow cytometry, bone marrow examination.