Anaemia

Overview

Definition:

Anaemia is the commonest haematological disorder seen in general medical practice

It is defined as haemoglobin concentration below the lower limit of normal for relevant population and laboratory performing test:

• In men aged over 15 years - Hb below 130 g/L.
• In non-pregnant women aged over 15 years - Hb below 120 g/L.
• In pregnant women - Hb below 110 g/L throughout pregnancy. An Hb level of 110 g/L or more appears adequate in the first trimester, and a level of 105 g/L appears adequate in the second and third trimesters.
• Postpartum - below 100 g/L.

Risk Factors

Risk factors are extremes of age, being female, pregnant or lactating. Although anaemia itself may cause morbidity, in the majority of cases it is secondary to an underlying disorder.

Investigations

Investigations should be aimed at identifying a possible cause before treatment or referral is considered. See Before Referral section below.

Who to refer

Please note that patients with iron deficiency anaemia should not be referred to haematology. Please see Anaemia (gastroenterology) page in the Gastroenterology and Colorectal Surgery chapter on Remedy.

Haematology referral is unlikely to be suitable for:

• Frailty - patients who are elderly or frail with mild (Hb ≥100g/l) unexplained asymptomatic anaemia (following exclusion of reversible causes and calculate creatinine clearance).  Consider monitoring these patients in the community. If concerns about an underlying haematological cause then consider using advice and guidance
• Iron deficiency anaemia - See Anaemia (gastroenterology) page for advice. Consider referral to gastroenterology, gynaecology or urology as directed by the clinical assessment. Except in premenopausal women, upper and lower GI investigations are likely to be appropriate. 
• Vitamin B12 or folate deficiency – See Vitamin B12 - guidelines (Remedy BNSSG ICB
• Anaemia of chronic disease - where haematinics are normal, an anaemia of chronic disease should also be considered - see the  Anaemia guidance on Patient.co.uk for further information - chronic infection, inflammation (eg rheumatoid arthritis), neoplasia and chronic kidney disease are the main culprit causes. Mild anaemia of chronic disease may not require any treatment.

 Consider referral for other conditions based on the advice in the Red Flag section below.

Red Flags

Refer via Haematology 2WW pathways as follows:

• A blood film report that suggests acute leukaemia (often associated with other cytopenias)
• A blood film suggestive of Chronic Myeloid Leukaemia (usually associated leukocytosis)
• Suspected Lymphoma or Myeloma

Urgency of referral will vary depending on various factors including degree of anaemia, rapidity of progression and presence of associated features, as well as frailty of patient.

• A blood film report that suggests a primary haematological disorder.
• With thrombocytopenia or neutropenia.
• Examination shows splenomegaly or lymphadenopathy.
• Reticulocytosis (without obvious bleeding). Raised LDH, bilirubin and low haptoglobin is consistent with haemolysis. Blood film and direct antiglobulin test (Coomb’s test) complete the assessment for this.
• Unexplained, progressive, symptomatic anaemia.
• A monoclonal protein (also known as paraprotein), abnormal serum free light chain assay or positive urine light chains (Bence Jones protein); usually the laboratory report guides further action.
• Unexplained MCV>105fl (see macrocytosis).

Before referral

General Assessment points in Primary Care

• The MCV helps to direct investigation for causes of anaemia.
• The reticulocyte count may be useful to differentiate between a red cell production defect (reduced) versus consumption or blood loss (elevated).
• Anaemia may be multifactorial, especially in the elderly.
• Transfusions should generally be avoided in patients with reversible causes (e.g. haematinic deficiency or haemolysis) unless there is cardiovascular instability. For other patients the decision to transfuse is based on degree of symptoms attributable to anaemia. Erythropoietin may be indicated in specific circumstances after discussion with the relevant specialist (e.g. renal physician, oncologist or haematologist).
• Assess historical FBC values.

Microcytosis/Microcytic anaemia:

Consider cause: often iron deficiency, may be thalassaemia / thalassaemia trait or anaemia of chronic disease.

Interpreting Ferritin results;

Ferritin results can be difficult to interpret - a ferritin below the reference range is diagnostic of iron deficiency. However iron deficiency can still exist with a normal ferritin especially if there is infection or inflammation present. Ferritin levels increase independently of iron status in acute and chronic inflammatory conditions, malignant disease, and liver disease.

• In the presence of anaemia a ferritin level of less than 30 micrograms/L confirms a diagnosis of iron deficiency.
• If ferritin < 100ug/l this could still be iron deficiency especially if an inflammatory condition, malignancy or liver disease is present in these patients:
  
  • Check CRP and  iron studies for transferrin saturation. Zinc protoporphyrin (ZPP) is not a reliable test of iron status and is no longer available.
  • Or/and 
  • If historically normal MCV, consider a trial of oral iron and then repeat FBC in 6-8 weeks to assess response. 

• If no previous normal Hb/MCV results, consider Hb electrophoresis to assess for β thalassaemia trait. Ethnic background may be informative. Hb electrophoresis may infer alpha thalassaemia trait.
• If iron deficiency is excluded on iron studies, or no response to iron, consider anaemia of chronic disease if there are comorbidities.

Normocytic anaemia: 

• Assess vitamin B12, folate, ferritin, renal function, liver function tests, reticulocyte CRP.
• Consider assessment of blood film, serum protein electrophoresis.
• If ferritin, vitamin B12 (See Vitamin B12 - guidelines (Remedy BNSSG ICB) or folate low, offer replacement and assess for a cause. If eGFR low, consider calculation of creatinine clearance (Cockcroft-Gault) as Cr Cl <40ml/min may cause anaemia.
• Consider clinical haematology advice or referral if no cause found or primary haematological cause likely.
• For older or frail people consider monitoring in the community following exclusion of reversible causes.

Macrocytosis/macrocytic anaemia - see also Macrocytosis page

• Review medical history – abnormal blood loss; diet; change in weight or bowel habit; gastric or terminal ilium surgery; medications; alcohol use, jaundice, liver disease.
• Assess vitamin B12 (take care with interpretation of levels considering clinical pre-test probability of a deficient state), folate, liver function tests, reticulocyte count and blood film.
• Consider assessment of serum protein electrophoresis, GGT, LDH, TSH.
• *Physiological changes in pregnancy may cause “anaemia”, that may be macrocytic. Investigation is unlikely to be informative unless marked macrocytosis (>105fl) or anaemia (<105g/l) without iron deficiency.
• Offer appropriate replacement if clear evidence of vitamin B12 or folate deficiency. Assess for a cause. See Vitamin B12 - guidelines (Remedy BNSSG ICB)
• Consider referral to a clinical haematology service if likely primary haematological condition or no cause established.
• For older or frail people consider monitoring in the community following exclusion of reversible causes.

Treatment

Treatment is dependent on the underlying cause but management of symptomatic patients while awaiting investigation may be required.

Generally, healthy individuals tolerate extreme anaemia well, with cardiovascular status being the major limiting factor. In haemodynamically stable patients without active bleeding, Hb levels between 70 g/L and 90 g/L were well tolerated with equivalent or lower mortality/morbidity outcomes compared with a liberal transfusion trigger of <100 g/L. It is generally recommended that determination of transfusion requirements be based upon severity of illness parameters rather than arbitrary Hb levels.

Blood transfusion

If transfusion support for symptomatic care is considered appropriate direct arrangements with local Medical Day Care / Ambulatory Care facility may be made. Please see Blood Transfusions and iron infusions page of Remedy.

Iron replacement

If a patient has iron deficiency anaemia then consider iron replacement if required (while investigations of cause are completed). See the Iron Deficiency Anaemia page for details.

Referral

Referral should be made depending on initial investigations in primary care and likely underlying cause.

If haematology advice or referral is required then please consider the following options:

URGENT ADVICE: 9am to 5pm via hospital switchboard for haematology SpR. ONLY for emergency advice. Out of hours and weekends – emergency advice may be obtained from the on-call haematology clinician via hospital switchboard.

NON-URGENT ADVICE: use Haematology advice and guidance service  via eRS. Your query should be responded to by a consultant haematologist within 5 working days. Please only use this service once the guidelines above have been followed and include relevant information and investigation results.

OUTPATIENT REFERRAL: via e-RS if appropriate or following advice and guidance.

SUSPECTED CANCER (2WW) : See Haematology - USC (2WW) page and/or red flags above. Ensure that the location and size of any lymphadenopathy is described. 

Minimal information: the referral letter should include abnormal clinical findings (location, size, any associated features) and any abnormal full blood count results or other relevant test results, particularly if these investigations were not done in laboratories of the hospital to which the referral is made.

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

Information provided through Remedy is continually updated so please be aware any printed copies may quickly become out of date.