Macrocytosis

Overview

Definition

A Mean corpuscular volume (MCV) >100fl. However, clinically relevant findings are more likely with more elevated levels, especially if MCV >110fl.

Macrocytosis is a term used to describe red blood cells that are larger than normal. Also known as megalocytosis or macrocythemia, this condition typically causes no signs or symptoms and is usually detected incidentally on routine blood tests.(1)

Macrocytosis isn't a specific disease, but it may indicate an underlying problem that requires medical evaluation. Possible causes of macrocytosis are listed below:

Potential causes

• Storage/transport artifact (consider if MCV is at or fluctuates around upper limit of normal, especially if no other abnormality in the FBC or clear cause)
• Excess alcohol consumption
• Liver disease
• Medications (cytotoxics e.g. hydroxycarbamide; immunosuppressants e.g. azathioprine or certain anti-retroviral agents).
• Reticulocytosis
• Vitamin B12 and /or folate deficiency
• Presence of a monoclonal protein (parapotein)
• Myelodysplastic syndrome (or other bone marrow disorders including myeloma)
• Pregnancy can cause macrocytosis and Hb below the “normal range” (physiological not pathological): investigations only required if significant (MCV>108) or associated with anaemia (Hb<105 g/L) in the absence of iron deficiency.  Interpretation of B12 level in pregnancy (or the COCP) is uncertain, avoid testing unless clinical features strongly suggest B12 or folate deficiency.
• Hypothyroidism is a rare cause.

Who to refer

Referral to secondary care is usually not required unless there are red flags (see Red Flag section below).

Scenarios where a haematology referral is not required include:

• Elderly, frail patients with an isolated macrocytosis (absence of cytopenias, haemolysis or myeloma) - consider monitoring in the community rather than referral. Haematology advice and guidance may be helpful if there are concerns about an underlying haematological cause.
• Vitamin B12 or folate deficiency is not an indication for referral for haematology outpatient assessment. See the Vitamin B12 - guidelines (Remedy BNSSG ICB) for further advice. Features suggesting a malabsorption syndrome may need specialist GI assessment.

Red Flags

The following conditions/scenarios may warrant referral or a request for advice and guidance:

• Suspected myelodysplastic syndrome (based on blood film report) - refer via eRS marked urgent (not 2WW).
• Other primary haematological cause suspected.
• MCV > 100fl with accompanying cytopenia (excluding vitamin B12 / folate deficiency).
• Persistent unexplained MCV > 105fl.

Before referral

Consider the following investigations in Primary Care prior to referral or requesting advice and guidance:

• Alcohol history and appropriate lifestyle modification
• Vitamin B12 and folate levels - consider sequential Intrinsic Factor antibodies (before giving pareternal vitamin B12 replacement) and coeliac screen. See Vitamin B12 - guidelines (Remedy BNSSG ICB) for further advice.
• Blood film examination and reticulocyte count.
• Liver and thyroid function test.
• Serum protein electrophoresis.

Referral

Referral is usually not required so please use the guidelines above to investigate and manage in primary care if appropriate and only request advice and guidance or refer if there are red flags or ongoing concerns.

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 

REFERRAL: through NHS e-referral system

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.

Resources

(1) Macrocytosis: What causes it? - Mayo Clinic

(2) Macrocytosis and Macrocytic Anaemia Information | Patient

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.