Macrocytosis and Macrocytic Anaemia
Macrocytosis means that the blood cells are larger than normal. When the macrocytosis is combined with a lower than normal haemoglobin, this is known as macrocytic anaemia.
What are the symptoms?
Macrocytes are the big guys of the blood cell world. Providing they have enough sense to carry around an amount of haemoglobin (the protein that makes sure oxygen gets to all your relevant bits) appropriate to their, size they won't in themselves cause you any problems.
Problems arise when each macrocyte contains less haemoglobin than it should, Then you are into symptoms of anaemia. It's a bit like the love child of that Monday morning feeling and the worst hangover you've ever had. You'll feel tired, get puffed out when you try to exercise, and your heart may start thumping. A doctor checking you out may notice you look pale, have an unnaturally strong pulse and a heart murmur.
Read more about the symptoms of macrocytosis and macrocytic anaemia.
What are the causes?
This is where it gets complicated. You can have macrocytosis with or without anaemia. Macrocytosis with anaemia can be divided up again depending on whether a pathologist looking down a microscope can or cannot see megaloblasts on a blood film. Megaloblasts are eternal teenagers, forever wanting to mature into fully formed red blood cells but unable to do so.
Macrocytosis without anaemia, macrocytic megaloblastic anaemia and macrocytic non-megaloblastic anaemia all have different causes, although the causes can overlap. Lack of vitamin B12 or folic acid is often involved somewhere along the line although liver disease, alcohol excess and medication can also be implicated.
Is that all clear? Good. Now perhaps you can explain it to me.
Learn more about the causes of macrocytosis and macrocytic anaemia.
How is the diagnosis made?
People have blood tests for all different reasons and sometimes macrocytosis with or without anaemia shows up on a blood film quite by chance.
Needless to say, if it does show up you're then in for lots of other blood tests, but most of them can be done through one needle.
You might need to have a bone marrow sample taken but the odds of that are pretty slim. You stand more chance of hearing a politician answer the question that's been put to them.
Find out more about how macrocytosis and macrocytic anaemia are diagnosed.
What treatment options are available?
If you've been found to have a deficiency, this will need to be treated. If it's vitamin B12, you'll probably end up having injections. If you don't like needles, it's tough but you need to realise that if the deficiency is left untreated you can develop all sorts of complications. The injections will be every other day to start with but eventually every few months, so it won't be so bad. Tablets are available but if your deficiency is due to difficulty in absorbing B12 through the stomach you might as well chew on a Smartie®.
Folic acid deficiency will also need treating but this time you can have tablets.
Whatever caused the deficiency in the first place will also need treating. If it was booze, you need to lay off the booze. Easier said than done, but help is available from your doctor and a variety of local services accessible in the community.
Read more about the treatment of macrocytosis and macrocytic anaemia.
What is the outlook?
Outlook (prognosis) depends on the cause but is better in younger, otherwise fit, people.
Learn more about the outlook for macrocytosis and macrocytic anaemia.
What are the symptoms of macrocytosis and macrocytic anaemia?
Macrocytosis does not cause any symptoms itself.
Macrocytic anaemia causes symptoms that you get with any other kind of anaemia. If it's mild you may not get any symptoms. You're more likely to notice symptoms if you are older or have coronary heart disease. Younger people can be quite anaemic without noticing any problems at all.
Symptoms you may notice include:
- Breathlessness on exercise.
- The sensation of a 'thumping' heart (palpitations).
- Symptoms of heart failure.
If you have angina, you may notice your chest pains getting worse.
If your macrocytic anaemia is due to vitamin B12 deficiency you may also notice nervous system problems such as pins and needles, numbness, vision changes and unsteadiness. You may also develop psychological problems such as depression and confusion. Normally these symptoms only develop if the deficiency is severe and it has been left untreated for a long time.
A doctor examining you may notice that you:
- Look paler than normal (the nails and tongue are a good place to check).
- Have a bounding pulse (a pulse which feels stronger and more powerful than normal).
- Have signs of heart failure.
- Have a heart murmur between the left second and third ribs when the heart is contracting (a pulmonary flow murmur).
You may notice some of these signs yourself.
What are the causes of macrocytosis and macrocytic anaemia?
Macrocytosis without anaemia can be caused by:
- Medicines such as azathioprine.
- Alcohol dependency.
- Vitamin B12 deficiency.
- Folate deficiency.
- Non-alcoholic liver disease.
Depending on severity and how long the person has had the condition, some of these causes can eventually lead to anaemia.
There are two types of macrocytic anaemia:
- Megaloblastic macrocytic anaemia
- Non-megaloblastic macrocytic anaemia
The difference is in the presence or absence of megaloblasts. These are large, abnormally developed red blood cells visible when a pathologist uses a microscope to look at a slide smeared with blood.
Causes of macrocytic megaloblastic anaemia include:
- Serum B12 deficiency (when associated with a low haemoglobin, this is called pernicious anaemia).
- Surgery that removes a part of the stomach (gastrectomy) or part of the gut called the ileum (ileal resection) causing difficulty in absorbing vitamin B12 from the diet.
- Infection of the gut with germs (bacteria) or parasites (organisms that live in the body and obtain nutrition from it).
- HIV infection.
- Deficiency of vitamin B12 in the diet - this can happen in strict vegans but even then it is rare.
- Folic acid deficiency. This can be due to:
- Not eating enough foods containing folic acid. Foods high in folic acid include broccoli, Brussels sprouts, asparagus, peas, chickpeas and brown rice.
- Conditions affecting the gut - for example, coeliac disease.
- Inflammatory conditions such as Crohn's disease.
- Some blood disorders can lead to a very high turnover of red blood cells - for example, sickle cell disease and thalassaemia. Normal amounts of folic acid in the diet may then not be enough and supplements may need to be taken.
- Some medicines interfere with folic acid. Therefore, you may need to take extra folic acid whilst taking certain medicines. These include colestyramine, sulfasalazine, methotrexate and some anticonvulsant medicines used to treat epilepsy. If you need dialysis then you may be recommended to take folic acid supplements.
Causes of macrocytic non-megaloblastic anaemia include:
- Alcohol dependency.
- Liver disease.
- Severe underactivity of the thyroid gland (hypothyroidism).
- An increase in the number of immature red blood cells called reticulocytes (reticulocytosis).
- Other blood disorders including myeloid leukaemia, aplastic anaemia (a condition affecting the bone marrow) and some other rare blood conditions.
- Medicines that affect how the genetic material DNA is produced, such as azathioprine.
How are macrocytosis and macrocytic anaemia diagnosed?
These conditions will show up on a blood film. Your doctor may have arranged this test as part of a routine check or because you have felt unwell (see the section called Symptoms). Once the condition has been diagnosed, further tests will be arranged to find the cause. You may also need tests to check whether you have any conditions that people who have macrocytosis or macrocytic anaemia frequently develop.
The tests may include:
- A reticulocyte count. This may be raised if there is a rapid turnover of red blood cells - for example, in conditions in which red cells are destroyed, such as haemolytic anaemia. If you're found to have such a condition, more tests (for example, a Coombs' test) may be needed to investigate the cause.
- The level of folate in your blood.
- The level of serum B12 in your blood.
- Tests of your liver function.
- Checks to rule out conditions which people with some types of macrocytic anaemia develop, such as diabetes, underactive thyroid, and homocystinuria (a condition in which a chemical called homocystine and related substances build up in the blood and urine).
- If some blood disorders are suspected, you may need a bone marrow examination, but this is the exception rather than the rule.
- Other tests may be needed if your doctor suspects other conditions need to be ruled out.
What are the treatment options for macrocytosis and macrocytic anaemia?
If it has been identified that your macrocytosis is caused by a deficiency, this will need to be treated, whether or not you have anaemia.
You will also need treatment for the condition that caused the deficiency in the first place.
If you have vitamin B12 deficiency you will usually be offered an injectable form of the vitamin called hydroxocobalamin. Your doctor or practice nurse will usually inject this into a muscle
You will need the injections every other day for a couple of weeks and then every 2-3 months for life. If you have symptoms related to the nervous system, you will need injections every couple of days until your symptoms improve and then every couple of months.
B12 tablets (cyanocobalamin) are also available but do not work very well if your deficiency is due to difficulties with absorption. However, they are sometimes recommended in rare cases where the deficiency is due to lack of vitamin B12 in the diet. They can be stopped if the amount of B12 in the diet increases. A dietician may be able to help you with this.
If you have folic acid deficiency you will be advised to take folic acid tablets. 5 mg daily for four months is usually sufficient after which the dose may be reduced. If you have severe deficiency you may require folate injections for a while.
If you have vitamin B12 and folic acid deficiency it's important that the B12 deficiency is treated first; otherwise, serious spinal cord complications (subacute combined degeneration of the cord) can occur.
Treatment of the underlying cause will depend on the condition. For example, if your deficiency was due to excessive use of alcohol, this will need to be addressed.
What is the outlook for macrocytosis and macrocytic anaemia?
The outlook (prognosis) will depend on the underlying cause. In most cases of B12 or folic acid deficiency, the outlook is good once the deficiency is corrected, providing the underlying cause (for example, excessive alcohol use) can be addressed. Older people tend to have a worse outcome than young fit people. A study suggests that older people with macrocytic anaemia don't do as well as those with microcytic anaemia (in which blood cells are smaller than usual, often due to iron deficiency).
Further reading & references
- Thakkar K, Billa G; Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur J Clin Nutr. 2015 Jan;69(1):1-2. doi: 10.1038/ejcn.2014.165. Epub 2014 Aug 13.
- Guidelines for the diagnosis and treatment of cobalamin and folate disorders; British Committee for Standards in Haematology (2014)
- Riva E, Colombo R, Moreo G, et al; Prognostic value of degree and types of anaemia on clinical outcomes for hospitalised older patients. Arch Gerontol Geriatr. 2017 Mar - Apr;69:21-30. doi: 10.1016/j.archger.2016.11.005. Epub 2016 Nov 14.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited has used all reasonable care in compiling the information but makes no warranty as to its accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Laurence Knott
Dr John Cox