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Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias R
Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias • diagnosis and management of macrocytosis and macrocytic anaemia in adults • other types of anaemia (see iron deficiency anaemia and Haemolytic anaemia • use of folate supplementation for other indications • macrocytosis refers to a raised mean cell volume resulting from enlarged erythrocytes • macrocytosis can exist alone or with anaemia. Macrocytosis without anaemia is often due to causes other than vitamin B12 and • vitamin B12 or folate deficiency is the most common cause of megaloblastic anaemia (a type of macrocytosis in which DNA • pernicious anaemia is the most common cause of vitamin B12 deficiency • pernicious anaemia has an incidence of 1:10,000 in Northern Europe • prevalence of vitamin B12 or folate deficiency has been reported as approximately 5% in those between age 65-74 years and more than 10% in those age 75 years or older • of those with vitamin B12 deficiency, approximately 10% also had low folate levels Risk factors/aetiology for folate deficiency: • inadequate dietary intake, eg due to alcoholism • certain drugs, eg colestyramine, sulfasalazine, methotrexate • inflammation, eg Crohn's disease, malaria • blood disorders, eg haemolytic anaemia Risk factors/aetiology for vitamin B12 deficiency: • most common is pernicious anaemia (impaired absorption of vitamin B12 due to lack of intrinsic factor [IF]) – pernicious anaemia is often familial (30% of cases have a family history) • autoimmune disorders, eg Crohn’s disease • inadequate dietary intake, eg due to veganism Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias Quick info:This pathway has been locally developed for South West Hampshire.
Quick info:At SUHT, a macrocytosis is an MCV of > 100 fl.
• the probability of vitamin B12 or folate deficiency increases as the MCV rises, and especially if MCV >130fl • patients receiving hydroxycarbamide usually have MCV >110fl and do not need further testing • MCV 100-110fl are more likely to be related to causes other than vitamin B12 or folate deficiency Quick info:The more common causes of macrocytosis are: • the following drugs can worsen, but not cause, vitamin B12 deficiency: • drugs such as methotrexate, azathioprine and hydroxycarbamide An isolated macrocytosis also occurs with cigarette smoking.
Quick info:At SUHT, anaemia is defined as: Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias • hypogranular neutrophils/no hypersegmented neutrophils suggest myelodysplasia • hypersegmented neutrophils and macro-ovalocytes associated with vitamin B12 and folate deficiency • uniform macrocytosis, often with stomatocytes, associated with alcohol abuse • target cells associated with liver disease • polychromasia associated with haemolysis • hypogranular neutrophils/no hypersegmented neutrophils suggest myelodysplasia • hypersegmented neutrophils and macro-ovalocytes associated with vitamin B12 and folate deficiency • uniform macrocytosis, often with stomatocytes, associated with alcohol abuse • target cells associated with liver disease Quick info:Further possible investigations should be based on blood film report and presence/absence of anaemia.
In the absence of anaemia, or changes on the blood film consistent with vitamin B12 or folate deficiency, then consider the followinginvestigations initially: • if taking methotrexate, azathioprine or hydroxycarbamide, no further investigations required in the absence of anaemia • serum vitamin B12 and serum folate assays • especially if malabsorption, severe oropharyngeal ulceration, neuropsychiatric abnormalities such as paraesthesia, ataxia, Quick info:Further possible investigations should be guided by the blood film, but may include: • reticulocyte count (raised in haemolysis or active bleeding) • serum vitamin B12 and serum folate assays • especially if malabsorption, severe oropharyngeal ulceration, neuropsychiatric abnormalities such as paraesthesia, ataxia, Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias Quick info:Biochemical hypothyroidism is characterised by: • thyroid stimulating hormone (TSH) levels greater than 10 mU/L with free thyroxine (FT4) levels low or normal; or • TSH above normal but less than 10 mU/L with normal FT4 in presence of unexplained symptoms consistent with • serum vitamin B 12 less than 160ng/L indicates deficiency • if vitamin B12 is low normal (160-180ng/L) then deficiency cannot be excluded, and repeat measurement 3 months later If there is co-existent folate and vitamin B12 deficiency, vitamin B 12 should be replaced before folate. Administration of folate inB12 deficient patients can precipitate acute combined degeneration of the cord.
• green vegetables and liver contain folate • look for low calcium (reduced vitamin D absorption) and low iron • coeliac disease (ferritin and tissue transglutaminase) • chronic inflammation (consider vasculitis) Quick info:If the above investigations are normal, check: • plasma protein electrophoresis looking for a paraprotein If no abnormality is identified, then myelodysplasia is a possibility. Either discuss with a haematologist or refer to the generalhaematology clinic if the patient has a symptomatic anaemia.
Local administrative info:
Classification of anaemias
SUHT consultants:
Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias • Dr Andrew Duncombe: Tuesday afternoons • pernicious anaemia (impaired absorption of vitamin B12 due to lack of intrinsic factor [IF]) is the most common cause – pernicious anaemia is often familial (30% of cases have a family history) • other (rare) causes or contributing factors include: • autoimmune disorders, eg Crohn’s disease • Medications that interfere with gastric acid production and can cause reduced absorption of B12 from ingested protein in food • inadequate dietary intake, eg due to veganism Check serum anti-intrinsic factor antibody: • highly specific for pernicious anaemia, but low sensitivity (50%) • if anti-intrinsic factor antibody is present, pernicious anaemia is very likely, but its absence does not rule out pernicious anaemia • sensitivity of anti-parietal cell antibody for pernicious anaemia is more than 90% – however, specificity is only 50% • in the absence of anti-parietal cell antibody it is unlikely that the person has pernicious anaemia • initial dose of levothyroxine usually 50-100micrograms daily, depending on body weight • adjust dosage by 25-50microgram increments • initial dose 25 micrograms daily if >50 years (especially those with ischaemic heart disease) and change dose by smaller • measure serum thyroid stimulating hormone (TSH) concentration after 6 weeks and titrate dose if needed • correct dose is that which restores the euthyroid state and relieves symptoms • dose of thyroxine aims to achieve TSH within lower half of the reference range Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias Give folic acid 5mg once daily for 4 months: • ensure there is no co-existent vitamin B12 deficiency - in such individuals, vitamin B 12 should be replaced before folate • administration of folate in B12 deficient patients can precipitate acute combined degeneration of the cord Quick info:Review after 4 months, with full blood count.
If cause of folate deficiency has been addressed, stop treatment. Otherwise, consider long term treatment Quick info:Consider seeking specialist advice in pregnancy or if there are neurological symptoms.
• intramuscular (IM) injections of hydroxocobalamin on alternate days for 2 weeks Long-term treatment where the underlying cause is not dietary: • IM injections of hydroxocobalamin every 3 months for life Long-term treatment where the underlying cause is dietary: • oral cyanocobalamin tablets daily between meals (available as a food supplement, and only prescribable on FP10 under special circumstances with 'SLS' endorsement required- see BNF); or • twice-yearly hydroxocobalamin injection (may be preferable in the elderly who are more likely to have malabsorption) • in vegans, this treatment may need to be life-long • in non-vegans treatment can be stopped once vitamin B12 levels have been corrected and diet has improved • advise consumption of foods rich in vitamin B12, eg: • foods fortified with vitamin B12 – some soy products, and some breakfast cereals and breads Quick info:Full blood count (FBC) and reticulocyte count should be performed after 10 days to check response to treatment: • there should be a rise in the haemoglobin level and an increase in the reticulocyte count to above normal range • if there is no improvement, check serum folate level (if this has not already been done) FBC after 8 weeks to confirm normal blood count Further monitoring is generally considered unnecessary – exceptions to this are: • suspected lack of compliance with treatment Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.
Macrocytosis and macrocytic anaemiasMedicine > Haematology and haemostasis > Macrocytosis and macrocytic anaemias Published: 19-May-2011, by Southampton Area Published: 19-May-2011 Valid until: 19-May-2012 Printed on: 01-Aug-2011 Map of Medicine LtdThis care map was published by Southampton Area. A printed version of this document is not controlled so may not be up-to-date with thelatest clinical information.

Source: http://www.hampshire.nhs.uk/primary-care/mapofmedicine/Macrocytosis%20and%20macrocytic%20anaemias-1.pdf