Blood cells have a limited lifespan and an estimated 100 billion new blood cells are required daily in order to maintain a healthy, steady state (Huether & McCance 2008). Consequently, haematopoiesis is a continual process which takes place in different anatomical sites throughout the lifespan. These include the embryonic yolk sac, the fetal liver and spleen, and in all bone marrow during infancy. From childhood onwards, red bone marrow is progressively replaced with fat. In adults haematopoiesis occurs primarily in the medullary cavity of flat bones. Sites include the:

• ends of the humerus and femur

• pelvis

• vertebrae

• ribs

• sternum

• skull.

Additional sites may be recruited when there is an increased demand for blood cells such as in the case of illness.

Blood constantly circulates around the body and the normal total blood volume depends on the size of the individual, e.g. 5–6 L in an average adult male. Blood is composed of both cellular and fluid elements.

Blood groups

ABO blood groups

Red blood cells have specific inherited antigens (also known as agglutinogens) on their membrane. These are important in terms of defining the ABO blood group classification system and a person can possess the A or B antigen, neither, or both. As such there are four main blood groups: A, B, AB and O.

A person with the antigen A (blood group A) has anti-B antibodies (also called agglutinins) in the plasma whereas a person with antigen B (blood group B) has the anti-A antibodies. A person with both antigens A and B (blood group AB) has no antibodies in the plasma, whilst a person with neither A nor B antigens (blood group O) has both anti-A and anti-B antibodies in the plasma (Table 11.1).

Table 11.1 Antigens and antibodies present in ABO blood groups

ABO Blood Group	Antigen on Red Blood Cell Membrane	Antibodies Present in the Plasma
A	A	Anti-B
B	B	Anti-A
AB	A and B	None
O	None	Anti-A and anti-B

The importance of the A and B antigens is evident when one person receives blood from another. If a person receives a transfusion of ABO incompatible blood, the transfused red cells will clump together (agglutinate) and break down (haemolyse), which may be fatal. Thus, if the recipient’s plasma contains anti-B antibody, they must only receive blood from a group A or O donor.

WBCs and platelets also possess ABO antigens. Therefore, if a patient is to receive a transfusion of other cellular components, the correct blood group must also be used.

The Rhesus D factor

In the UK, 85% of the population have a second important class of antigen present on their red cells: the Rhesus (Rh) D factor. Thus a person may be either RhD-positive or RhD-negative.

The antibody, anti-D, does not occur naturally in the plasma of RhD-negative blood, but stimulation to produce it can occur if a RhD-negative person receives a RhD-positive blood transfusion or if, during pregnancy or childbirth, red blood cells from a RhD-positive fetus cross the placental barrier into the circulation of a RhD-negative woman. In these circumstances later exposure to RhD-positive red blood cells will result in agglutination and haemolysis. Blood products to be transfused must therefore be carefully cross-matched for the RhD factor as well as ABO groups.

Other blood groups

In addition to the ABO and RhD factor blood groupings there are several further blood classification systems, e.g. Duffy, Kell and other Rhesus antigens. These do not usually cause agglutination unless multiple blood transfusions are required, in which cases it would be essential to check that donor blood is compatible with the recipient’s blood serum antibodies.

(See Further reading, e.g. Daniels & Bromilow 2007.)

Blood transfusion

Blood transfusion, the administration of whole blood or blood products donated by one person to another, makes it possible to save lives. Transfusion does, however, expose patients to the risk of potentially fatal complications, e.g. infection, haemolytic reactions or receiving an incompatible unit of blood (Box 11.1). Box 11.2 provides an opportunity for you to consider how nurses can improve safety during transfusion.

Box 11.1 Reflection

Serious hazards of transfusion of blood and blood products

The SHOT (Serious Hazards of Transfusion) Annual Report 2007 analysed 332 adverse events. These included 46 ‘wrong blood’ events where a patient received a blood component intended for a different patient or of an incorrect group (SHOT 2007).

Activities

• Access the SHOT Annual Report 2007 and read more about the episodes where people were given a blood component of an incorrect group.

• Find out about the checks used when a sample of blood is taken for group and cross-match, and the tests and checks taken in the laboratory to ensure that blood of the correct group is supplied for the patient. Discuss these measures with your mentor.

Resource

SHOT (Serious Hazards of Transfusion) Annual Report 2007. Available online http:// www.shotuk.org.

Box 11.2 Evidence-based practice

Promoting safer blood transfusion

Results from a national audit of bedside transfusion practice revealed that patients in the UK are at risk of misidentification and poor monitoring when undergoing a blood transfusion. Parris & Grant-Casey (2007) identify the implications of the audit findings and explore initiatives to improve blood transfusion safety.

Activities

• Access the article by Parris & Grant-Casey (2007) and list the key recommendations for improving safety during blood transfusion.

• Consider your own practice area. What could be done to ensure that all staff members involved in the administration of blood products comply with these guidelines?

See website Critical thinking question 11.1

Many people who require blood transfusions fear being infected with a transmittable disease, such as HIV, hepatitis or variant Creutzfeldt–Jakob disease (vCJD). It is therefore necessary that the screening procedures undertaken on all blood donors and the testing and processing of donated blood are explained. For instance, in the UK, white cells are routinely removed from donated blood to minimise the risk of transmitting vCJD. Some religious groups such as Jehovah’s Witnesses may refuse blood transfusions while some others may wish to consult family and religious leaders before giving consent. The blood transfusion products readily available are listed in Table 11.2.

Table 11.2 Blood transfusion products available

Product	Indications for Use	Special Points
Whole blood (infrequently given)	Acute, severe bleeding requiring replacement of red blood cells and plasma and coagulation factors	Stored at 4°C for up to 35 days Platelets and coagulation factors have much reduced viability
Fresh whole blood (infrequently given)	As above	Blood <24 h old, therefore more likely to contain viable coagulation factors
Red cell concentrate	Replacement of red blood cells only. Therefore used when haemoglobin level is low	Up to 200 mL plasma removed per 500 mL blood
Washed red cells	As for red cell concentrate Specially prepared to remove antigens	Prevents anaphylactic transfusion reactions
Frozen red cells	As for red cell concentrate	Storage lifespan lengthened, therefore useful for rare blood groups
Platelet concentrate	Patients with platelet count <20 × 10⁹cells/L but not actively bleeding	Platelet units from blood banks contain platelets from many units of blood, therefore there are frequent reactions. Patient may require i.v. hydrocortisone plus i.v. chlorphenamine prior to transfusion. Stored at 20°C. Viability of platelet concentrate only 24 h. Never place in fridge
Other blood components
Fresh frozen plasma	Hereditary or acquired bleeding disorder Volume replacement Liver disease Disseminated intravascular coagulation (DIC)	Frozen within 6 h of cell separation and viable for 1 year. Once thawed, use within 30 min
Cryoprecipitate (factor VIII, fibrinogen)	Haemophilia	From fresh frozen plasma Last part to thaw is cryoprecipitate
Factor VIII	Haemophilia A	From fresh frozen powder (half-life 12 h)
Factor IX	Haemophilia B (Christmas disease)
Human immunoglobulin	Passive immunity, especially immunosuppressed patients
Albumin solution	Hypoproteinaemic oedema, ascites, acute volume replacement

Before a patient receives a transfusion of a blood product their blood is grouped. The donated blood is then tested for compatibility with that of the recipient. The donor’s blood should be of the same ABO blood group and a RhD-negative recipient should receive RhD-negative blood products. Details of the cross-matching are recorded along with the blood unit number on the documentation sent with the unit of blood. After the transfusion, this documentation is retained in case of a transfusion reaction. Patients may be able to donate their own red cells prior to elective surgery. This is known as an autologous transfusion and avoids the risks associated with allogeneic blood transfusions.

(See Further reading, e.g. Gray & Illingworth 2005.)

Disorders of the blood

The following sections address a range of blood disorders affecting RBCs, WBCs and platelets. Although the specific responsibilities of nurses caring for patients with blood disorders will depend on their particular role and workplace setting, key elements will include:

• detecting and monitoring signs of illness and response to treatment

• assisting with medical investigations

• administering treatment and supportive therapies

• providing information and patient education

• health promotion regarding nutrition, lifestyle and the prevention of complications

• assessment and management of pain

• implementing strategies aimed at infection prevention and control

• providing emotional support and reassurance

• liaising with and making referrals to multidisciplinary health team members.

Investigations used in the diagnosis of blood disorders

A range of investigations are used for the diagnosis of blood disorders, Specific tests will depend on the nature of the suspected disorder but may include:

Blood tests

• Full blood count (FBC) – to establish the total number of red cells, white cells and platelets.

• Haemoglobin concentration – a level 10% below normal is considered indicative of anaemia.

• Packed cell volume (PCV) or haematocrit – the volume of red blood cells expressed as a percentage of the total volume of blood.

• Reticulocyte (immature RBCs) count – a small percentage are normally present in the blood, but a larger percentage may indicate increased bone marrow activity if the red cell count is low.

• Mean cell volume (MCV) – measures the average red cell volume.

• Mean cell haemoglobin (MCH) – measures the average haemoglobin concentration.

• Erythrocyte sedimentation rate (ESR) – measures the rate of fall of red cells in plasma left standing for an hour.

• Ferritin (an iron storage protein) – measures the amount of iron stores.

• Vitamin B₁₂ and folate.

Blood film

This is the examination of blood cells under a microscope to examine cell morphology in order to detect abnormalities in their size, structure or shape.

Bone marrow aspiration and trephine biopsy

This involves the removal of a small amount of bone marrow from the posterior iliac crest or sternum. This is mounted on slides and stained for microscopic examination. This test is not done routinely but is indicated if there is evidence of severe anaemia or of another blood disorder such as aplastic anaemia or leukaemia (Box 11.3).

Box 11.3 Information

Bone marrow aspiration

Purposes

• Diagnosis – to examine cell populations and thus determine type of anaemia, leukaemia or lymphoma.

• Monitoring – to assess progress of disease and response to treatment.

Sites

Red bone marrow is found in the cavities of the flat bones of the adult, e.g. skull, clavicle, scapula and iliac crest. The site usually chosen (for ease of access to minimise trauma to nearby structures) is the iliac crest – left and right, anterior and posterior.

The nurse’s role

The patient may be anxious about this investigation, especially if there is awareness that the results may show a malignant condition. This anxiety may be heightened if the patient has been talking with others who have undergone the procedure.

Providing the patient with information on all aspects of the test – the use of premedication and local anaesthetic, the site to be used, the degree of discomfort to be expected, the time that it will take, and when the results will be reported – will help to reduce anxiety.

It is the policy of some doctors, especially where repeated aspiration will be required, to give a sedative such as lorazepam or a light general anaesthetic. The individual may undergo the procedure as an outpatient, inpatient or as a day case. Whatever the setting, the nurse’s role will include:

• assessing the patient’s understanding of the test and providing more information if necessary

• ensuring that the patient’s platelet count has been checked prior to the procedure and that the results are available

• preparing the equipment

• ensuring that the patient is comfortable and is positioned correctly

• observing the patient throughout the procedure and drawing attention to any change in condition

• assisting the doctor

• applying a pressure dressing and making the patient comfortable after the procedure

• inspecting the aspiration site frequently for signs of haemorrhage or haematoma formation

• documenting the patient’s response to the procedure

• preparing the patient for discharge by explaining care of puncture site, what discomfort may be expected, who to contact if ill-effects arise, when results will be available and timing of the next appointment.

Possible complications

• Haemorrhage – the patient’s platelet count should be checked before aspiration.

• Infection.

Other investigative techniques

These include cytogenetic studies, immunophenotyping and molecular studies which assist in the detection of chromosomal and genetic abnormalities and are important prognostic indicators for many haematological malignancies.

Disorders of red blood cells – anaemias (general aspects)

Anaemias are a complex group of blood disorders found in all age groups resulting from a reduction in the number of RBCs and/or haemoglobin concentration in the blood (Figure 11.3). Defined by the World Health Organization (WHO et al 2001) as haemoglobin level less than 13.0 g/dL in males over 15 years of age, less than 12 g/dL in non-pregnant females over 15 years and children aged 12–14 years, and less than 11 g/dL in pregnancy, anaemia may be caused by:

• decreased red cell production

• excessive destruction of red cells

• chronic or acute blood loss.

Figure 11.3 Main types of anaemia.

Anaemia may be the primary presenting illness or may occur secondary to another condition such as cancer, chronic renal failure or an inherited disorder of haemoglobin synthesis. Anaemia may also be acquired due to environmental, iatrogenic or nutritional factors.

Interestingly, many people are diagnosed with anaemia by chance when they seek medical advice for an unrelated symptom or during a routine medical examination.

Pathophysiology

Anaemia arises when the oxygen-carrying capacity of the red blood cells is reduced. Symptoms stem from a lack of oxygen in the tissues and are primarily due to compensatory mechanisms which occur in response to hypoxia (reduced levels of oxygen in the tissues). The severity of symptoms will depend on the haemoglobin concentration of the red blood cell and the ability of the person to adapt to a lower oxygen concentration.

Clinical presentation

The clinical presentation of anaemia is diverse and each type of anaemia has specific attributes. However, features common to all types include:

• tiredness and lethargy

• dizziness, fainting and dimness of vision

• headache and lack of concentration

• angina and/or intermittent claudication.

Investigations

Blood samples will be taken for FBC, haemoglobin level, MCV, MCH, ESR, PCV, serum iron and blood film. Bone marrow aspiration is not undertaken routinely but is indicated if the anaemia is severe.

Treatment

Treatment will depend on the cause, type and severity of anaemia. Some patients may need to be hospitalised but most can be treated in the community with medication, lifestyle changes and health education. The underlying cause of the anaemia must also be treated. Blood transfusions may be needed either initially or repeatedly over a period of time. Follow-up care for all anaemic patients is important to encourage and monitor compliance with medication and to prevent recurrence and long-term adverse effects.

Nursing management and health promotion: anaemia

Patients may experience some general problems common to most anaemias in addition to those specific to their type of anaemia. This section outlines the nursing management of general problems. The specific problems and nursing management are discussed in subsequent sections. It is vital that the patient is treated as an individual and that care is holistic. A nursing assessment of the patient’s background, lifestyle, illness, needs and goals should be undertaken, after which a care plan will be agreed.

General problems associated with anaemia

Tiredness

Patients may tire easily because of hypoxia. It is important that their daily routine in hospital or at home includes periods of rest. If cardiac failure is evident, the patient may need to be nursed in bed or in a chair. The nurse should be aware of the potential problems of immobility, paying particular attention to pressure areas and the prevention of venous thromboembolism (VTE). Assistance with personal hygiene and dressing may also be needed. Patients should be reassured that their tiredness is not imaginary but is part of the anaemia and that it will lessen as treatment progresses.

Breathlessness

Breathlessness may be mild, occurring only on exertion, or it may be a major problem causing considerable distress and debility. Nursing priorities will focus on ensuring maximum perfusion of oxygen to the tissues and reducing the patient’s distress. These can be achieved by nursing the patient in an upright position, administering oxygen as prescribed, explaining to the patient the reason for the breathlessness and giving reassurance that it will lessen as the anaemia improves.

Nutrition

The anaemic patient will require a high-protein diet which includes all the nutrients necessary for red cell production (p. 368). Breathlessness, a lack of energy to shop and prepare food, a sore mouth and dysphagia may all contribute to anorexia. A sore mouth can be especially distressing and the nurse will need to carry out an oral assessment using an appropriate assessment tool. Care should include not only that which will improve and heal the mouth but also relevant health education about oral hygiene including teeth cleaning and/or care of dentures, mouth washes and lip care.

Patients who have a low income and/or a poor understanding of nutrition may need referral to a dietitian or specialist nutritional nurse for specific guidance about nutrition and diet. A social worker referral may also be needed for advice about budgeting and social security benefits.

Safety

Faintness, light-headedness and sensitivity to cold make the anaemic patient prone to injury. As the body responds to poor oxygenation by preserving the blood supply to the essential organs, anaemic patients will have poor peripheral circulation and, consequently, fragile skin. The reduced attention span typical of anaemic patients will also make them vulnerable to falls, minor injuries and hypothermia. Anaemic patients should be warned against changing position suddenly, especially from lying to standing, and should be given instruction on first aid for minor injuries and on the prevention of hypothermia (see Ch. 22).

Skin integrity

The anaemic patient’s reduced oxygen and nutrient supply to the skin increases the risk of pressure ulcers. Hypoxic skin will not necessarily break down quickly, but if damaged it will take longer than usual to heal. An initial and continuing assessment of all pressure areas should be made using appropriate risk assessment tools (see Ch. 23).

Once the patient’s level of risk of developing pressure ulcers has been determined, appropriate interventions should be instigated. These will include ensuring that the patient’s position is changed 2 hourly, the use of appropriate pressure-relieving devices and instructing the patient about the importance of regular re-positioning (European Pressure Ulcer Advisory Panel [EPUAP] 2008).

Anxiety and communication

Prior to diagnosis, the anaemic patient may fear the presence of a life-threatening illness, particularly if frightening symptoms such as breathlessness, palpitations and chronic headaches have been experienced. The disorientation and confusion arising from cerebral hypoxia can be distressing. Explanation of the causes of these symptoms and reassurance that they should improve as the anaemia responds to treatment may help to reduce the anxiety suffered by both the patient and the family.

Specific anaemias

The section outlines some specific anaemias: iron deficiency, megaloblastic, aplastic, haemolytic including the inherited haemoglobinopathies (sickle cell disease and thalassaemia), and anaemia caused by blood loss.

Iron deficiency anaemia

Iron deficiency anaemia affects an estimated 600 million people (Craig et al 2006) and is recognised as one of the most common types of anaemia worldwide.

Pathophysiology

Iron is a constituent of haemoglobin and is essential for cellular function and erythropoiesis. Iron deficiency anaemia arises when absorption of iron from food does not meet the daily requirements. This may be due to chronic blood loss (discussed more fully on pp. 375–376) or malabsorption, although the most common cause is inadequate dietary intake (Mehta & Hoffbrand 2009).

Clinical presentation

As the onset of iron deficiency anaemia is usually very gradual, the patient may not seek medical attention until some time after symptoms appear. The most common presenting features are tiredness and pallor, although any of the other general symptoms of anaemia (see p. 373) may be apparent. Signs and symptoms specific to iron deficiency anaemia include:

• glossitis – a smooth, sore tongue

• hair thinning

• angular cheilosis – maceration at the angles of the mouth

• koilonychia – spoon-shaped (concave) and brittle nails

• pica – a strong desire to eat unusual substances such as ice or coal.

Medical management

History and examination

The patient may give a history suggestive of inadequate iron intake or chronic blood loss, e.g. menorrhagia or bleeding from the gastrointestinal tract. Examination may reveal general signs of anaemia.

Investigations

Blood samples will be taken for tests, such as FBC, haemoglobin level, MCV, MCH, ESR, blood film, serum iron and total iron-binding capacity (TIBC). Estimates of ferritin (an iron storage protein) measure iron stores and a subnormal level is caused by iron deficiency (Craig et al 2006). Other investigations such as faecal occult blood testing (FOB), endoscopy or barium studies may be undertaken to establish the cause of the deficiency.

Treatment

If dietary changes are insufficient to correct the anaemia, oral iron (ferrous salts) supplements, usually ferrous sulphate, will be prescribed. Medication should be continued for 3–6 months after the haemoglobin level has returned to normal to replenish iron stores. Side-effects, which include constipation, nausea, abdominal pain and diarrhoea, often lead to poor compliance with medication and these should be explained to the patient. Intramuscular iron injections are usually given only where there is proven malabsorption syndrome or poor compliance. If the anaemia is very severe (less than 7 g/dL) blood transfusions may be required.

Nursing management and health promotion: iron deficiency anaemia

Many of the nursing considerations for the general care of anaemic patients (see pp. 373–374) are relevant for iron deficiency anaemia. Other nursing management strategies will focus on patient education and discharge planning with an emphasis on health promotion.

Patient education and health promotion

Helping the patient to understand the disorder will assist in promoting compliance with treatment. Information about foods that are rich in available iron should be given and advice on selecting and budgeting for a well-balanced diet may also be needed (Box 11.4). Assessing the patient’s perception of the problem, level of knowledge and sociocultural background can help to ensure that the advice offered is relevant and comprehensible. Referral to a social worker may also be appropriate.

Box 11.4 Reflection

Nutrition and the prevention of iron-deficiency anaemia

Tom is 45 years old and has been diagnosed with iron deficiency anaemia. He tells you that he works as a long-distance lorry driver and is often away from home for long periods of time. Subsequently he does not eat regular meals and most of his diet comprises chips, sweets and take-away meals.

You have been asked to provide Tom with advice about his diet and improving his intake of iron-rich foods.

Resource

Food Standards Agency Iron deficiency. Available online (June 2009): http://www.eatwell.gov.uk/healthissues/irondeficiency/?lang=en.

Clear instructions should be given to reinforce the prescriber’s directions regarding medication. Patients should also be made aware that ferrous salts of iron cause blackened stools and discolouration of the urine.

If inpatient treatment has been required the following should be discussed with the patient and family/carers before discharge:

• conditions at home and the availability of support services if family or friends are unable to help

• the importance of follow-up appointments with health professionals

• the importance of taking prescribed medication.

In older people, there is often a link between recent bereavement and the onset of iron deficiency anaemia, as loneliness, grief and depression may lead to self-neglect. Such patients should have the necessary follow-up and support by the health visitor, social worker or bereavement support counsellor.

Anaemia resulting from chronic blood loss

Iron deficiency anaemia may result from blood loss. This may either be:

• acute – the loss of a large volume of blood over a short period of time, as in haemorrhage (Chs 18, 27), or

• chronic – the loss of small amounts of blood over an extended period of time.

Chronic blood loss, which will be addressed in this section, is not uncommon and may present secondary to a number of other disorders. Frequently, it is only when a diagnosis of iron deficiency anaemia has been established that the underlying cause is suspected. The most common causes of chronic blood loss are listed in Box 11.5.

Box 11.5 Information

Common causes of chronic blood loss

Gastrointestinal blood loss is the commonest cause in men and postmenopausal women (Craig et al 2006).

Genitourinary bleeding (see Chs 7, 8)

• Menorrhagia (heavy regular menstrual flow) – a common cause.

• Haematuria – bladder cancer.

Respiratory bleeding (see Ch. 3)

• Chronic haemoptysis – lung cancer, tuberculosis, bronchiectasis, pulmonary infarction.

Pathophysiology

It is unlikely that ill-effects of chronic blood loss will be noticed until it has caused depletion of the body’s iron stores. The pathophysiology is similar to that of iron deficiency anaemia caused by poor dietary intake of iron (see p. 374).

Clinical presentation

In addition to those of iron deficiency anaemia, clinical features of anaemia occurring as a result of blood loss occur in accordance with the underlying disorder. Examples include indigestion, abdominal pain, menorrhagia, weight loss, blood in stools or haematuria.

Medical management

History and examination

Investigations

These are as for the diagnosis of iron deficiency anaemia (see p. 374).

Treatment

Treatment will depend on the specific cause of the blood loss; however, treatment options include oral iron preparations to replenish iron stores and possibly blood transfusion.

Nursing management and health promotion: anaemia due to chronic blood loss

The patient may be feeling apprehensive and frightened, and providing clear information about investigations, especially invasive procedures such as endoscopy (see Ch. 4), may help to alleviate anxiety. Information should address any pre-investigative preparation such as fasting, approximate durations of tests and what they will involve. It is also important to discuss whether the patient will be fit to return home unaccompanied after investigative procedures and when the results can be expected.

When planning care, the nurse must prioritise the patient’s needs and be sensitive to their individual values and perceptions. Comprehensive assessment will help to establish the cause of bleeding and this will incorporate sensitive questioning, observation, monitoring of vital signs and discussion with the patient’s family and friends as appropriate.

Megaloblastic anaemias

Megaloblastic anaemias are characterised by large, immature and dysfunctional RBCs (megaloblasts) in the bone marrow.

Pathophysiology

Megaloblastic anaemias are due to defective DNA synthesis, commonly caused by a deficiency of either:

• vitamin B₁₂ (cobalamins), or

• folates (group of B vitamins).

Although in these conditions the haemoglobin content of the cells is typically normal, the defective cells have a considerably reduced lifespan, which decreases their numbers in the bloodstream resulting in anaemia.

Vitamin B₁₂ deficiency

As vitamin B₁₂ is found predominantly in meat, eggs and dairy products, vegans are at particular risk; however, the most common cause of vitamin B₁₂ deficiency is malabsorption due to pernicious anaemia. This condition, caused by autoimmune gastritis, affects 1 in 100 people of all races over the age of 60 (Hoffbrand & Provan 2007). It occurs when the gastric mucosa atrophies, resulting in a failure to produce intrinsic factor required for vitamin B₁₂ absorption. Table 11.3 outlines other causes.

Table 11.3 Causes of the megaloblastic anaemias

Type	Causes
Folate deficiency	Inadequate dietary intake
	Malabsorption: • disease of small bowel, e.g. coeliac disease, extensive surgical resection of small bowel • alcohol misuse
	Increased demands: • very active cell proliferation, e.g. in haemolytic anaemia or leukaemia
	• pregnancy
	Excessive loss: • heart failure • long-term dialysis Drugs: • the cytotoxic drug methotrexate • antiepileptic medications, e.g. phenytoin • oral contraceptive
Vitamin B₁₂ deficiency	Inadequate vitamin B₁₂ in diet (especially vegans) Malabsorption: • reduced gastric acid (hypochlorhydria) • gastric surgery • pernicious anaemia caused by autoimmune gastritis that leads to gastric atrophy and intrinsic factor deficiency • pancreatic insufficiency • inflammatory disease of terminal ileum where vitamin B₁₂ is absorbed, e.g. Crohn’s disease • small bowel resection involving the ileum

Folate deficiency

Folates are found in green leafy vegetables, potatoes, fruits, fortified breakfast cereals and bread, liver, milk and dairy products, and yeast extract. Deficiency is commonly due to an inadequate dietary intake of folic acid. (See Table 11.3 for other causes.) This may occur either alone or in conjunction with a condition such as pregnancy, in which folate utilisation is increased. Fetal abnormalities, e.g. neural tube defects (NTDs), are associated with inadequate folate intake around the time of conception and during the first few weeks of pregnancy.

Clinical presentation

As vitamin B₁₂ and folic acid are essential for all dividing cells, a deficiency of these not only affects RBCs but also the gastrointestinal epithelium, leading to glossitis, anorexia, diarrhoea and malabsorption. In addition to these and other general signs of anaemia, megaloblastic anaemia may cause mild jaundice and skin pigmentation.

Pernicious anaemia develops gradually so the condition may be very advanced when treatment is sought. Because vitamin B₁₂ is important for myelin production, up to 40% of people with this deficiency may develop spinal cord damage or peripheral nerve problems causing:

• paraesthesia

• coldness or numbness in limbs

• ataxia

• atrophy of optic nerve

• dementia.

Medical management

History and examination

History and examination is similar to that for anaemia (see p. 373). However, if megaloblastic anaemia is suspected the doctor will be alert to a history of gastrointestinal surgery, alcohol misuse or epilepsy and to the following specific features identified above.

Investigations

Blood tests will be similar to those for the diagnosis of iron deficiency anaemia (see p. 374) Additional specific diagnostic blood tests for megaloblastic anaemia include serum B₁₂ levels and folate assays. Other investigations may include:

• gastric parietal cell antibodies

• Schilling test (to determine cobalamin absorption)

• endoscopy

• bone marrow aspiration (see Box 11.3)

• neurological examination (see Ch. 9).