Essential haematology

Stephen French and Arun Kochhar explain how to interpret blood results

The full blood count is one of the most common medical investigations, and it can give important information to help support or refute a diagnosis that doctors have made based on clinical history and examination. The full blood count gives information about red cells (erythrocytes), white cells (leucocytes), and platelets.

Normally the cell counts are maintained in a steady state because the number produced by bone marrow (in haemopoiesis) is similar to the number destroyed by the reticuloendothelial system (the spleen, liver, and bone marrow). When this steady state is disrupted, cell counts may become abnormally increased or decreased.

Red cells

Red blood cells have a lifespan of about 120 days, in which they transport oxygen from the lungs to body tissues and carbon dioxide back to the lungs. The kidneys produce the hormone erythropoietin, which stimulates the bone marrow to produce red blood cells.

Anaemia occurs if the concentration of haemoglobin falls below the reference range for the age and sex of a person and arises from an imbalance between production and destruction of red cells. Symptoms of anaemia depend on how long the anaemia has been present and how severe it is. Symptoms can vary greatly between people and may include tiredness, decreased exercise tolerance, and shortness of breath. Pallor (paleness) of the conjunctiva indicates anaemia.

Anaemia can be simply classified according to the mean cell volume as microcytic (<76 fl), normocytic (76-96 fl), or macrocytic (>96 fl). This helps to determine the cause of the anaemia.

Microcytic anaemias result from defects in haemoglobin synthesis, the most common cause of which is iron deficiency. Common causes include chronic blood loss, such as by excess uterine bleeding in women of reproductive age (menorrhagia) or gastrointestinal bleeding--for example, from a peptic ulcer or carcinoma of the stomach, colon, or rectum. Koilonychia (spoon shaped nails) indicates chronic iron deficiency anaemia.

It is important, however, to remember that anaemia may not be present after acute major blood loss because circulating volume has not been replaced--this can take up to 24 hours.

Other causes of iron deficiency anaemia include increased demand during pregnancy, chronic disease, bone marrow infiltration (caused by leukaemia, myeloma, metastatic carcinoma, or fibrosis), or combined iron and folate deficiency. Renal failure may result in normocytic anaemia due to failure to produce erythropoietin.

The anaemia of chronic disease results from retention of iron in tissue stores as an adaptive response to chronic infection, inflammation, or malignancy. Mean cell volume may be normal or low and the degree of anaemia is related to the severity of the underlying disorder. Haemoglobin concentration, however, is rarely less than 8.0 g/dl so that the anaemia itself is seldom a major clinical problem. Causes of this type of anaemia include tuberculosis, pulmonary abscess, rheumatoid arthritis, and malignancy.

Macrocytic anaemias (with a mean cell volume >100 fl), are usually due to folate or vitamin B-12 deficiency. These vitamins are required for DNA synthesis and deficiency is characterised by abnormal cell division and accumulation of large ineffective immature cells termed megaloblasts in the bone marrow. Liver disease may also cause macrocytic anaemia, as can certain anticancer drugs. Aplastic anaemia and myelodysplasia are rarer causes.

Macrocytosis (mean cell volume >96 fL without low haemoglobin) may be due to chronic excess alcohol ingestion (associated with a raised gamma glutamyl transferase in liver function tests).

Further investigation of anaemia would try to identify the underlying cause as suggested by findings in the history and clinical examination.

Polycythaemia is a raised red cell count, increased haemoglobin and haematocrit (packed cell volume). It may be absolute (due to increased red cell mass with maintained plasma volume), or relative (due to maintained red cell mass with decreased plasma volume--for example, vomiting, diarrhoea, diuretics, burns).

Absolute polycythaemia may be primary (due to increased production--for example, polycythaemia rubra vera) or secondary (due to increased erythropoietin production). Possible causes of secondary polycythaemia include smoking, chronic lung disease, cyanotic congenital heart disease, time spent at high altitude, or renal lesions leading to inappropriate erythropoietin production. Again, clinical findings will help to differentiate between these causes.

White cells

Neutrophils are the principal defence against many acute bacterial infections. These infections result in an increase in their numbers (neutrophil leucocytosis). Other important causes of neutrophil leucocytosis include acute inflammation and tissue necrosis (for example, infarction, trauma, burns), acute haemorrhage, and myeloproliferative disorders (for example, chronic myeloid leukaemia). This is because neutrophils are recruited to sites of tissue damage by chemoattractants such as complement and their numbers therefore increase. Certain drugs, notably corticosteroids, may also cause a raised neutrophil count. Neutrophil leucocytosis is the most common abnormality of white blood cells.

Neutropenia (a selective decrease in numbers of neutrophils) may result from impaired bone marrow function or excess consumption in overwhelming infection or autoimmune disorders such as systemic lupus erythematosus. Bone marrow suppression may result from primary haematological conditions, such as leukaemia, or more commonly after treatment of other malignancies with cytotoxic drugs. Idiosyncratic reactions to other drugs such as certain anti-inflammatory medication, antibacterial treatment, and anticonvulsants may also result in neutropenia. Note that circulating neutrophil concentrations are lower in black people, being between 1.0 and 1.5*10⁹, compared with about 2*10⁹ in white people. There is substantial risk of serious infection when the neutrophil count falls below 0.5*10⁹ and the presence of fever in these patients is an indication for urgent admission to hospital for empirical therapy with broad spectrum antibiotics under the supervision of a haematologist.

An increase in the numbers of lymphocytes (lymphocytosis) is seen in many viral infections, including infectious mononucleosis (glandular fever), in which the high lymphocyte count is associated with the presence of large atypical mononuclear cells. A marked lymphocytosis is often seen in children with whooping cough, and, in older people, the commonest cause of lymphocytosis is chronic lymphocytic leukaemia.

A reduction in the number of lymphocytes (lymphopenia) is found after the administration of corticosteroids or other immunosuppressive treatment, immune deficiency syndromes such as HIV/AIDS, and after high dose radiotherapy or chemotherapy. Other conditions which may result in lymphopenia include severe bone marrow failure--for example, due to infiltration by carcinoma, and Hodgkin's disease.

Eosinophils appear to be selectively used for fighting parasitic infections, and may also be raised in allergic disorders, such as asthma, hay fever, eczema, and urticaria. This would appear to be mediated by cytokines.

Platelets

Platelets are formed in the bone marrow by the fragmentation of the cytoplasm of megakaryocytes. Their main function is to form a plug at sites of damage to vascular endothelium.

A low platelet count (thrombocytopenia) may be due to decreased platelet production, increased destruction of platelets, or abnormal distribution of platelets in splenomegaly. Platelet production may be decreased by bone marrow infiltration, aplastic anaemia (see box), excess alcohol, vitamin B-12 or folate deficiency leading to megaloblastic anaemia, or after anticancer treatment. Increased destruction of platelets may be seen in various autoimmune diseases (such as systemic lupus erythematosus or idiopathic autoimmune thrombocytopenic purpura) or in disseminated intravascular coagulation (disseminated intravascular coagulation, often due to severe bacterial septicaemia resulting in release of procoagulant material into the bloodstream). Patients with thrombocytopenia are susceptible to prolonged bleeding from cuts and to purpura and bleeding from mucous membranes.

A high platelet count (thrombocytosis) may be seen in chronic myeloproliferative disorders, or it may be reactive, as a result of recent infection or haemorrhage or underlying chronic inflammatory or malignant disease.

Pancytopenia

Pancytopenia refers to a simultaneous reduction in circulating numbers of red blood cells, white blood cells, and platelets. This reduction may be due to failure to produce sufficient numbers of cells. This may be caused by bone marrow infiltration, severe vitamin B-12 or folate deficiency, HIV infection, or aplastic anaemia.

Increased peripheral destruction of cells may also result in pancytopenia. Examples of causes include splenomegaly, overwhelming infection, systemic lupus erythematosus, and paroxysmal nocturnal haemoglobinuria. The latter is a rare disorder in which red blood cells, white blood cells, and platelet cell membranes are unusually sensitive to lysis by complement pathways. Clinical features include intravascular haemolysis, recurrent venous thromboses, and pancytopenia.

Information from the full blood count should be used in conjunction with the clinical history, examination, and other investigations to help formulate and distinguish between differential diagnoses.

Stephen French preregistration house officer, St Thomas' Hospital, London
Email: stephenfrench@doctors.org.uk

Arun Kochhar, third year medical student, Guy's, King's, and St Thomas' School of Medicine, London


studentBMJ 2004;12:393-436 November ISSN 0966-6494