Anaemia

Features of patients seen in a medical or surgical context

Medical conditions and treatments likely to cause anaemia in patients in the UK are: solid tumours; haematological malignancies; peptic ulcer and other GI conditions; myelodysplasia; anaemia of chronic disease; poor nutrition; and treatment with chemotherapy and/or radiotherapy for malignant conditions. In many parts of the world, anaemia is very common mainly due to poor nutrition, malaria and parasite infestation.

Investigation and the plan of management should take account of possible causes, the severity of fatigue and other symptoms, the impact of co-morbidities, any likely effect of Hb level on outcome of therapy, the availability of specific treatment for the underlying disorder (e.g. steroids for autoimmune haemolytic anaemia, antilymphocyte globulin for aplastic anaemia, and chemotherapy for acute or chronic leukaemia) and the potential benefit of epoetin therapy.

Nutritional anaemias

Patients with iron, B12 and folate deficiency anaemias may present with a haemoglobin level below 50 g/l. Even these low levels are tolerated by some patients, and for these transfusion may be avoided since effective haematinic therapy will raise the Hb rapidly, reaching near normal in four to six weeks. Patients with severe anaemia due to vitamin B12 deficiency should be transfused with caution (a single unit, over three to four hours with close observation). It is not possible to recommend any single Hb value as a transfusion trigger in this group of patients. Each case should be treated on the basis of thorough clinical assessment. Transfusion will correct the anaemia but will not correct the deficiency state. This must be treated fully to prevent recurrence.

Treatment of iron deficiency

Oral iron

A standard regime is ferrous sulphate 200 mg tds (180 mg elemental iron/day). Compliance with oral iron therapy is poor. Symptoms attributed to oral iron may be less if dose is reduced (e.g. 200 mg ferrous sulphate (65 mg of elemental iron) daily or 300 mg ferrous gluconate daily (35 mg of elemental iron)). If this is ineffective or not tolerated, parenteral iron may be considered.

Parenteral iron preparations

Indications: Severe iron deficiency anaemia with iron intolerance, malabsorption of oral iron or non-compliance with oral iron therapy. Patients with ongoing blood loss, anaemia of renal failure treated with epoetin.

Anaemia of chronic disease with EPO therapy, e.g. inflammatory bowel disease, rheumatoid arthritis.

Jehovah's Witnesses with iron deficiency and/or active blood loss.

Products: Two preparations are licensed in the UK: low molecular weight iron dextran (Cosmofer) and iron saccharate (Venofer).

Dosage and administration: Should be used according to manufacturer's directions and within local protocols.

Precautions

Immediate severe and potentially lethal anaphylactoid reactions can occur with parenteral iron-carbohydrate complexes. The risk is enhanced for patients with known (medical) allergy. When parenteral iron therapy is considered essential in patients with asthma, allergic disorders and inflammatory disorders, the intramuscular route is to be preferred.

CosmoFer® is an iron (III)-hydroxide dextran (low MW) complex. It may only be administered when anaphylactic emergency measures, including an injectable adrenaline solution, are available, i.e. adrenaline dose 0.5 ml of 1/1000 solution by intramuscular injection (www.bnf.org). Administration to patients with (auto)immune disorders or inflammatory conditions may cause a type III allergic reaction. Low MW iron dextran is associated with less adverse events than high MW dextran preparations.

Venofer® is an iron (III)-hydroxide sucrose complex. The most frequently reported adverse drug reactions (ADRs) in clinical trials were transient taste perversion, hypotension, fever and shivering, injection site reactions and nausea, occurring in 0.5 to 1.5% of the patients. Non-serious anaphylactoid reactions occurred rarely.

For dosage and administration, search www.emc.medicines.org.uk

Anaemia of chronic disease (ACD)

May contribute to anaemia in many situations where there is underlying malignancy, inflammation, sepsis and other conditions such as diabetes and congestive cardiac failure. The causes are a combination of: impaired marrow utilisation of iron; lower than expected rise in erythropoietin; blunted marrow response to erythropoietin; and erythroid activity suppressed by cytokines. These patients have an increased rate of transfusion as surgery or medical treatment commences with a lower haemoglobin level and with a poor endogenous response to anaemia. Intravenous administration of iron may allow correction of haemoglobin in some cases, and EPO therapy has also been successful, for instance, when used preoperatively in patients with rheumatoid arthritis awaiting joint replacement. Forward planning may reduce or eliminate the need for perioperative transfusion in some of these patients.

Anaemia in patients with cancer

Cancer may cause anaemia by infiltration of the bone marrow by cancer cells, impaired erythropoeisis due to inflammatory cytokines, nutritional deficiencies of iron, folate, blood loss into or from tumours, and kidney or liver damage, leading to reduced production of the hormone erythropoietin. Anti-cancer treatments, particularly platinum-containing drugs, can suppress the production of red blood cells in the bone marrow. Severe fatigue is perhaps the most commonly reported and debilitating symptom of anaemia in cancer. Other symptoms of anaemia, such as dizziness, shortness of breath on exertion, palpitations, headache and depression, also reduce the patient's quality of life. Many patients with cancer are anaemic at diagnosis. During treatment severity of anaemia fluctuates. It is typically worst two to four weeks after chemotherapy but depends on many factors, including the type of treatment and the number of courses. On completion of a course of treatment, haemoglobin tends to return to pre-treatment level, depending on how successful the treatment has been. In a large survey of patients with cancer, 39% had haemoglobin < 120 g/l at enrolment, 10% had haemoglobin < 100 g/l and 1% had haemoglobin < 80 g/l. More patients became anaemic during treatment. The quality of life of patients with malignancy-associated anaemia may be improved by regular allogeneic red cell transfusion. Red cell transfusion is often a mainstay of supportive therapy in malignant conditions predominantly associated with marrow failure (such as myelodysplasia, myelofibrosis and aplastic anaemia) or extensive marrow infiltration (such as chronic lymphocytic leukaemia). Specific haematinic supplementation may be of benefit in any patient in whom vitamin deficiency has been identified. Iron therapy is often poorly tolerated.

Epoetin in anaemic cancer patients

Human erythropoietin is a glycoprotein hormone produced in the kidney. Epoetin is being used to prevent and treat anaemia in cancer patients. A recent Cochrane review found consistent evidence that the administration of epoetin reduces the risk for blood transfusions and the number of units transfused in anaemic cancer patients. However, it was not clear to what extent epoetin treatment affects quality of life or survival in such patients. A recent randomised trial of epoetin in patients with head and neck cancer showed poorer survival in the epoetin-treated patients, and a trial in breast cancer was halted when more tumour progression was observed in the epoetin arm of the trial. Some cancer cells express epoetin receptors, and epoetin may stimulate tumour blood vessel formation. A cautious approach to the use of epoetin in cancer patients is appropriate given the current state of knowledge. NICE has renewed epoetin for anaemia in cancer patients (www.nice.org.uk).

Licensed indications for epoetin products are given in the BNF. Epoetin should be used according to local hospital protocols.