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Interpreting haematology test results

Consultant Kate Ryan outlines the more common tests and how GPs can best make use of them

haematology laboratory handbook should be available with details of tests provided, samples required and contact numbers for clinical advice.

Requests for tests must be accompanied by demographic and clinical data to allow appropriate interpretation to be made.

Under-filling or over-filling of bottles may produce inaccurate results due to dilutional effects; this is especially important for coagulation tests. Difficult venepuncture may produce aberrant results due to partial clotting or haemolysis.

Urgent or critically abnormal results, meeting laboratory-defined criteria, should be phoned or faxed back immediately. The requesting doctor must ensure there are mechanisms for dealing with these results both during and outside working hours. Reference ranges will vary according to age and sex.

What follows is a guide to interpreting the results of some of the more common tests.

Full blood count (FBC)

The laboratory will have defined criteria for blood film examination. A guide to appearances and their interpretation is given in the box above.

Anaemia

Anaemia is generally classified according to the mean cell volume (MCV) (see figure below).

Iron deficiency

This is the commonest cause of anaemia. In the

early stages iron stores become depleted with little effect on red cell indices. Investigations include:

 · Serum ferritin: a measure of iron stores;

levels are very low in overt iron deficiency;

levels may be artificially elevated with acute and chronic inflammatory conditions and

malignancy.

 · Serum iron and iron binding capacity: may help to distinguish between iron deficiency and anaemia of chronic disease (ACD).

Practice points:

 · A cause should always be sought for iron deficiency.

 · Oral iron usually results in a rise of Hb by 1g every 10 days.

 · Causes of failure to respond to therapeutic iron:

·insufficient dose ­ higher doses are needed for treatment and often produce dose-related side-effects

·non-compliance

·bleeding

·malabsorption

·ACD

·alternative diagnosis of thalassaemia trait (see below).

Macrocytosis

Common causes of macrocytosis are:

 · Alcohol

 · Liver disease

 · B12 or folate deficiency

 · Hypothyroidism

 · Primary bone marrow disorders such as myelodysplasia

 · Drugs.

Film appearances may suggest a diagnosis. Otherwise initial screening tests should include liver and thyroid function and B12/folate levels.

B12 deficiency

 · Clinical features of B12 deficiency may occur without marked haematological changes

and should always be considered in patients

with unexplained neurological or psychiatric symptoms.

 · A high proportion of vegetarian patients will have subnormal B12 levels without clinical deficiency and are able to absorb oral B12 normally. These patients should be given a trial of oral B12 and levels re-measured. If initial Hb is normal, it will take some weeks for the MCV to return to normal.

 · Most non-vegetarian cases are due to malabsorption, usually pernicious anaemia. Parenteral B12 should be given. Consider anti IF antibodies and refer for further assessment.

 · B12 levels are always high in those receiving B12 injections: Hb and reticulocyte count are better indicators of response to treatment. Failure to respond suggests an alternative cause such as myelodysplastic syndrome.

 · B12 levels may be low in pregnancy; results should be interpreted with caution.

 · Low levels are seen in primary folate

deficiency.

Anaemia of chronic disease

Generally a mild to moderate anaemia. More severe (eg, Hb less than 9g/dl) indicates an alternative diagnosis or an additional problem such as iron deficiency or drugs. Severe anaemia is seen in renal failure.

Polycythaemia

Hb levels do not vary much in adults. Mild variation is seen with dehydration and after vigorous exercise. Polycythaemia detected by an increased Hb and/or haematocrit may be due to primary causes, eg bone marrow proliferation, or secondary to hypoxic lung disease or EPO-secreting tumours. Apparent polycythaemia is common and due to reduced circulating plasma volume. This is associated with smoking, hypertension, alcohol and diuretic therapy. Investigation requires referral to haematologist.

Platelet abnormalities

 · Thrombocytopenia: common causes include viral infection (usually self-limiting), drugs, liver disease, ITP. It may also be seen towards the end of pregnancy in a proportion of healthy women. Patients with counts <50x109 are="" prone="" to="" spontaneous="" bleeding="" and="" should="" be="" referred="">

 · Thrombocytosis: most commonly reactive to underlying infection, inflammatory disorders and bleeding. Refer for investigation if no obvious cause or it is associated with raised WBC and/or Hb.

 · Platelets >1,000x109/l caused by myeloproliferative disorders increase the risk of thrombotic and bleeding complications.

ESR

 · Non-specific, age- and sex-related with considerable overlap between health and disease in the elderly.

 · Most use in monitoring chronic disease and its response to treatment. Limited use in screening.

 · Very raised levels seen in autoimmune disease, malignancy and papraproteinaemias.

 · For the elderly 35mm/hour is the upper reference range. The overlap with the levels for disease mean that it is not a good screen.

Haemoglobin electrophoresis

The most common Hb variants are structural, ie HbS or due to reduced production of normal Hb chains ­ the thalassaemias (common in certain ethnic groups but all racial groups may be affected).

Practice points:

 · Sickle cell trait is most commonly seen in Afro-Caribbeans. It is associated with normal Hb and does not cause symptoms.

 · Sickle cell disease is a severe lifelong disorder, usually with moderate to severe anaemia. Patients should be managed in specialist centres.

 · Thalassaemia trait is most commonly seen in Mediterraneans, Arabs and Asians and causes a mild microcytic anaemia, unresponsive to iron. Patients are asymptomatic. Do not give iron unless deficiency is confirmed.

 · Female patients with known haemoglobinopathy must be referred as early as possible in pregnancy for partner testing and genetic counselling.

 · It is important to ensure women, particularly those of appropriate ethnic background, are screened in early pregnancy.

Parasitic screening

 · Malaria is diagnosed by identifying parasites in thick and thin blood films. Identification may be difficult if the patient has been partially treated.

 · Repeat samples should be sent if initial screening is negative and clinical suspicion remains.

 · Some antimalarials are associated with haemolysis in G6PD deficiency (seen in Mediterranean, Asian and African patients); therefore males of appropriate ethnic groups should be screened.

Coagulation investigations

Most cases of easy bruising are not associated with coagulation problems. A lifelong or family history of excessive bleeding (eg from unusual sites or excessive amount of normal bleeding) may point to inherited disorder and should be referred for specialist opinion. Initial tests should include a coagulation screen and platelet count. Drugs causing a functional defect should also be considered.

Practice points for anticoagulant therapy with warfarin:

 · Warfarin is monitored by INR and each patient will have a defined target range depending on the underlying indication.

 · Requirements may change over time ­ even stable patients should be checked every eight to 12 weeks.

 · Drug interactions are important. Consult BNF or equivalent. Do not withhold therapy if necessary but arrange INR check if potentiating drug is continued after five days.

 · Warfarin effect is accentuated in liver disease and with alcohol. A patient with history of alcohol excess or liver disease should be monitored frequently.

 · Bleeding or bruising on warfarin: check INR and omit if high. Seek advice from anticoagulant clinic.

 · Bleeding from unusual sites may indicate underlying pathology and should be investigated.

Thrombophilia screening

A tendency to thrombosis (thrombophilia) may be hereditary and associated with a family history or acquired in an individual, for example malignancy, autoimmune disorders.

Screening for hereditary thrombophilia should be performed in conjunction with a haematologist for correct interpretation of results and appropriate counselling.

Practice points:

 · The main value of screening is to identify individuals at risk of VTE and to offer appropriate advice and prophylaxis in high-risk situations, eg surgery, pregnancy.

 · Thrombophilia screening is not recommended before COC or HRT use in women with no personal or family history of thrombosis.

 · Screening should be offered to individuals with a strong family history of thrombosis in first-degree relatives especially if considering the OCP or if an abnormality has been identified in a family member.

 · A negative result from screening does not preclude thrombophilia: patients with a personal history of thrombosis should be considered at high risk of further thrombosis regardless of results from thrombophilia testing.

 · Testing for hereditary thrombophilia is not usually helpful in arterial disease.

Blood film appearances and their meaning

Finding Significance

Microcytes Iron deficiency, thalassaemia traits

Macrocytes Alcohol, liver disease, B12/folate deficiency

Polychromasia Reticulocytosis, eg, bleeding, haemolysis, response to haematinic

therapy

Elliptocytes Iron deficiency

Target cells Liver disease, haemaglobinopathies, hyposplenism, iron deficiency

Spherocytes Immune haemolysis, hereditary spherocytosis

Dimorphic picture Haematinic treatment, sideroblastic anaemia

Reactive lymph nodes Viral infection

Atypical lymph nodes Infectious mononucleosis, viral infections, toxoplasmosis

R shift Hypersegmented neutrophils, eg, megaloblastic anaemia

L shift Immature myeloid cells ,eg, infections, leukaemia reactions

Smear cells Chronic lymphocytic anaemia

Toxic granulation Infections and inflammatory disorders

Leucoerythroblastic Immature red and white cell precursors, eg, metastatic malignancy

and myelofibrosis

White cell abnormalities (common causes of leucocytosis and leucopenia)

White cell finding Cause Comment

Neutrophilia Bacterial and other infections Neutrophil L shift and toxic granulation may be seen in severe

Inflammation infections

Myeloproliferative disorders and chronic myeloid leukaemia Associated with raised Hb, platelet count, eosinophilia

Eosinophilia Parasitic infections Stool examination if no apparent cause, especially in children

Allergy and skin conditions

Drugs

Vasculitis

Hodgkin's disease

Monocytosis Chronic infections, eg, TB

Myelodysplastic syndromes and chronic myelomonocytic leukaemia

Lymphocytosis Viral infections Atypical lymphocytes

Infectious mononuclosis Morphology often characteristic

Lymphoproliferative disorders, eg, chronic lymphocytic leukaemia

Neutropenia Viral infections, HIV Repeat in two-three weeks

Ethnic variation Counts <1x109 prone="" to="">

Drugs Unexplained neutropenia should be referred for investigation

Bone marrow disorders, eg, myelodysplastic syndrome

Interpreting haematology test results

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