HOW I DO – Anemia – PART – 26
HOW I DO – Anemia – PART – 26
(All the articles published in past are available at www.shyamhemoncclinic.com/blog/)
Question: In last part, we discussed some important points related to anemia with high MCV 1. Anemia with MCV over 120 is almost always B12 deficiency in our country. 2. Peripheral smear showing macro ovalocytes along with high MCV is near confirmatory for B12 deficiency anemia. 3. Sublingual B12 replacement is preferred. other option is subcutaneous injection. one may also use intramuscular or intravenous. 4. Studies from India are not conclusive with regard to cause of B12 deficiency. Possibly due to low intake, but not clear. Prevalence of B12 deficiency is very high in India. 5. Once a year blood test is recommended to screen for vitamin deficiency. For those who have deficiency, regular supplements as outlined in last part are important. Daily high doses are NOT recommended. What are the other common causes of anemia with high MCV?
Answer: Good question. After B12 deficiency, the next most important one to think of is folate deficiency. Folate and B12 deficiency look almost identical on blood counts and smear, both give macro ovalocytes, both can give high MCV, both can even give mild pancytopenia in severe cases. The difference is mainly in history. Folate deficiency is seen more in people with poor diet, chronic alcohol use, pregnancy, hemolytic anemia with high cell turnover, or malabsorption states. Nowadays isolated folate deficiency is less common than B12 deficiency in our practice, likely due to better diet for most people. When in doubt, or when B12 replacement alone does not correct the anemia, it is reasonable to add folate as well, or check folate level directly. In practice, most of our supplements contain folic acid as well.
Que: Ok, that make sense, why check both if history overlaps, and supplents also include both. What about causes other than vitamin deficiency?
Ans: Yes, this is important, as not all high MCV anemia is nutritional. Hypothyroidism is a common cause, and easy to miss if not specifically looked for. Any patient with unexplained macrocytic anemia should get a TSH done, especially if there is associated fatigue, weight gain or menstrual irregularity. Correcting the thyroid status corrects the anemia over some months. Chronic liver disease and chronic alcohol use are two other important causes, and often go together. Alcohol has a direct toxic effect on bone marrow, in addition to the poor diet and folate deficiency it commonly causes. Liver disease itself, independent of alcohol, changes the red cell membrane lipid composition and increases MCV. So in a patient with high MCV, always ask about alcohol history and look for signs of chronic liver disease.
Que: What about medicines? You mentioned some drugs causing low MCV anemia in earlier part.
Ans: Yes, several medicines cause high MCV anemia too, through different mechanism, mainly by interfering with DNA synthesis. Common ones we see are hydroxyurea, used for conditions like polycythemia, essential thrombocythemia, and sickle cell disease. Other drugs are some chemotherapy agents, azathioprine, and older antiretroviral drugs like zidovudine. Anti-epileptic drugs, particularly phenytoin, can also cause macrocytosis, partly through interference with folate metabolism. So drug history is essential in any patient with unexplained high MCV.
Que: You had mentioned MDS as cause of low MCV in last part, does it also cause high MCV?
Ans: Yes, actually MDS more commonly presents with high MCV, not low. I had mentioned it in the low MCV part as one of the less common causes there, but classically it is a cause of macrocytic anemia, often with other cytopenias, and needs to be suspected in elderly patients with unexplained persistent macrocytic anemia not responding to vitamin replacement, especially with abnormal cells on smear or other cytopenias. This needs bone marrow evaluation to confirm.
Que: What about high MCV not due to marrow problem, like in bleeding or hemolysis?
Ans: Very good point, this is commonly missed. Any condition with high reticulocyte count, such as ongoing hemolysis or recovery after acute bleeding, will show high MCV. This is because reticulocytes, or young red cells, are larger than mature red cells. This is not true macrocytosis of the marrow, but a reflection of high cell turnover. Reticulocyte count is hence an important test in the workup of high MCV anemia, along with peripheral smear. If reticulocyte count is high, direction of workup shifts towards hemolysis or bleeding, rather than deficiency or marrow disease.
Que: So how should a family physician approach this practically?
Ans: I would suggest, in any patient with high MCV anemia, get history for diet, alcohol use, drug use, and symptoms of hypothyroidism. Examine for jaundice, and signs of chronic liver disease. Send B12, TSH, and reticulocyte count together, along with peripheral smear. This covers the vast majority of causes. If all these are normal, or if anemia does not improve with appropriate replacement, then referral for further workup, including possible bone marrow evaluation, is needed.
August 2026 Dr Chirag A. Shah; M.D. Oncology/Hematology (USA), 9998084001. Diplomate American Board of Oncology and Hematology. Ahmedabad. drchiragashah@gmail.com www.shyamhemoncclinic.com