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Macrocytosis –An increase in the mean cell volume ( MCV) above the normal range Upper range may be quoted as 95-100 fl. Prevalence ranges from 1.7 % to 5 % Up to 60-80 % with macrocytosis may not have anaemia
Main causes- Alcohol B12 and or folate deficiency Medications Hypothyroidism ( rarely ) Bone marrow dysplasias Liver disease ( non-alcoholic ) Reticulocytosis Physiological ( neonates , pregnancy ) Unexplained
Macrocytosis with anaemia – Alcoholism Liver disease Hemolysis with bleeding Hypothyroidism Folate or B12 deficiency Exposure to chemotherapy and other drugs Myelodysplasias Hereditary haemochromatosis Plasma cell dyscrasias
Macrocytosis without anaemia – Take detailed history Alcohol Drugs Tests ( particularly reticulocyte count and peripheral smear ) About 10 % cases may remain unexplained even after evaluation
Drug induced megaloblastic anaemia- Modulate purine metabolism - ○ azathioprine ○ mycophenolate mofetil ○ mercaptopurine ○ methotrexate ○ allopurinol Interfere with pyrimidine synthesis ○ antineoplastic agents ( e. g . hydroxyurea , methotrexate ) ○ trimethoprim ○ leflunomide Decreased folic acid absorption ○ alcohol ○ aminosalicylic acid ○ contraceptive pills ○ estrogens ○ tetracyclines ○ penicillins ○ chloramphenicol ○ nitrofurantoin ○ erythromycin ○ phenobarbital ○ phenytoin ○ malaria drugs as quinine , chloroquine , primaquine Folate analogue activity ○ methotrexate ○ proguanil ○ trimethoprim Vit B12 – decreased absorption ○ isoniazid ○ metformin ○ proton pump inhibitors , H2 blockers ○ neomycin Unknown – sulfasalazine
Investigations – B12 and folate If available metabolites methylmalonic acid and homocysteine can be checked to determine true B12 deficiency If B12 deficient – check intrinsic factor antibody and gastric parietal cell antibody Blood film Reticulocyte count Liver function test Thyroid function test Lipids/ cholesterol Immunoglobulins and protein electrophoresis Urine for BJP Bone marrow biopsy
Referral –Suspected myelodysplasia syndrome ( based on blood film , myelodysplasia may progress to leukaemia ) Other primary haemotological cause suspected MCV > 100 fl with accompanying cytopenia ( excluding b12/ fol deficiency ) Peristent unexplained MCV > 105 fl ( this may vary some guidelines mention from 104 ) B12 deficiency of uncertain cause requiring further investigation
Elderly frail patients with isolated macrocytosis ( ie no cytopenias , haemolysis or myeloma ) consider monitoring in the community or advice from haematology Mild isolated macrocytosis ( < 105 fl ) in an otherwise fit patient – can be monitored in community
References
- Evaluation of Macrocytosis Am Fam Physician , 2009 feb 1;79(3):203-208
- Macrocytosis An Australian general practice perspective Australian Family Physician Vol. 36, No. 7, July 2007 571https://www.racgp.org.au/afp/200707/200707rumsey.pdf
- How do you evaluate macrocytosis without anaemia ? The Journal of Family Medicine Vol 57, No 8 / august 2008
- Drug-Induced Megaloblastic Anemia N Engl J Med 373;17 Oct 2015
- The Significance of Unexplained Macrocytosis Blood 2008 112:3449
- UH Bristol Haematology Referral Guidelines for Primary Care C Bradbury May 2016
- Macrocytosis GPOnline by Dr Cecil Reid November 2017