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Indian Journal of Medical Sciences
Medknow Publications on behalf of Indian Journal of Medical Sciences Trust
ISSN: 0019-5359 EISSN: 1998-3654
Vol. 58, Num. 7, 2004, pp. 309-311

Indian Journal of Medical Sciences, Vol. 58, No. 7, July, 2004, pp. 309-311

Presedential Address

Megaloblastic anemia - Part II

BSES MG Hospital and Holy Family Hospital, 6/32, Hari-Kripa, S. V. Road, Santacruz (W), Mumbai-400 054
Correspondence Address:BSES MG Hospital and Holy Family Hospital, 6/32, Hari-Kripa, S. V. Road, Santacruz (W), Mumbai-400 054 asshah@eth.net

Code Number: ms04057

CLINICAL FEATURES OF MEGALOBLASTIC ANEMIA

These can be classified into 2 categories -
(a) features of B12 and folate deficiency
(b) features due to the underlying cause

Features of B12 and folate deficiency

Hematologic abnormalities
The onset of symptoms of megaloblastic anemia is usually gradual as cobalamin reserves are large. Years may pass between cessation of cobalamin intake and appearance of deficiency symptoms.

Symptoms of anemia like weakness, fatigue, exertional dyspnea, palpitations, dizziness and aches and pains all over the body are commonly present. Glossitis and angular stomatitis are also common. There may be a mild icteric tinge. Hyperpigmentation over dorsum of the hands, or knuckles may also be seen. There may be mild hepato -splenomegaly.

Neurologic abnormalities
Neurological abnormalities occur only with B12 deficiency. Patients commonly present with paresthesias characteristic of peripheral neuropathy and glove and stocking type of anesthesia. In addition B12 deficiency can also cause degeneration of the posterior and lateral columns of the spinal cord and so the patient can present with a wide variety of features ranging from unsteadiness and inco-ordination of gait to ataxia and spastic paraplegia. Even the higher mental functions can be impaired and the patient may present with confusion and memory loss. Interestingly, extensive neurological damage can occur and minimal hematologic abnormalities, especially if the folate levels are normal. B12 deficiency in infancy is associated with mental retardation.

Folate deficiency during pregnancy is known to be associated with congenital anomalies, most notably neural tube defects.

Folate deficiency can also lead to elevated homocysteine levels which is a major risk factor for atherosclerosis and venous thrombosis.

Features of underlying cause
Patients also manifest with symptoms and signs of the underlying disorder causing B12 and folate deficiency eg: patients with malabsorption would have diarrhea, bulky and frothy stools and weight loss. They may also have features due to deficiency of other substances like edema feet due to protein deficiency, bone pains and tetany due to calcium and vitamin D deficiency etc. Similarly patients with hemolytic anemia would have features like hemolytic facies with frontoparietal and malar prominence, hepatosplenomegaly and symptoms suggestive of crises like abdominal pain and bone and joint pain. Patients with pernicious anemia may have symptoms of other autoimmune disorders like hypothyroidism, rheumatoid arthritis etc.

INVESTIGATIONS IN MEGALOBLASTIC ANEMIA

Complete hemogram
A routine complete hemogram is simple and cheap means of suspecting megaloblastic anemia. The hemoglobin is usually lower than normal and the mean corpuscular volume (MCV) is more than 100. The red cells on peripheral blood smear show evidence of macrocytosis. The reticulocyte count is usually normal but may be elevated occasionally. The White cell count may be normal or low. Neutrophil nuclei characteristically show hypersegmentation with more than 5 or 6 lobes. Platelet count may also be reduced. Thus in an appropriate clinical setting, pancytopenia with raised MCV and hypersegmented neutrophils would suggest the diagnosis of megaloblastic anemia. However if the patient has multiple deficiencies like iron deficiency coexisting with B12 and folate deficiency, these typical features may not be evident and diagnosis becomes difficult.

Estimation of cobalamin and folate levels
Estimation of B12 and folate levels in serum would help in establishing the diagnosis. Serum vitamin B12 level less than 100 pg/ml and serum folate level less than 5 ng/ml is diagnostic of B12 and folate deficiency respectively. Serum folate levels may be higher than expected in cobalamin deficiency and patients deficient in both B12 and folate may have normal folate levels. This is due to the fact that B12 deficiency blocks folate metabolism. Thus although the body folate stores are reduced, folate levels appear elevated due to blocked metabolism. Red cell folate level is a better indicator of tissue folate status and is low in folate deficient megaloblastic anemia.

Bone marrow examination
The bone marrow in frank megaloblastic anemia reveals macronormoblastic maturation and giant mtelocytes and metamyelocytes i.e. precursors of red cells and white cells which are larger in size compared to normal.

Investigations to determine the cause of B12 and folate deficiency
A detailed dietary history helps us to identify nutritional deficiency as the cause of megaloblastic anemia.

Absorption of B12 can be tested by Schilling test. The patient is given 0.5 ìCi of radioactive cobalamin and 24 hour urine collection is begun to measure the amount of cobalamin excreted. The patient is also given 1mg of cobalamin parenterally to saturate the stores. Normal subjects excrete more than 7 % of total radioactivity in the first 24 hours. If excretion is low, second part of Schilling test is performed. The procedure is same exceptthat active intrinsic factor is also given orally along with radiolabelled B12. If poor excretion in the first part of Schilling test is due to lack of intrinsic factor, excretion in the second part of the test would be normal. Intrinsic factor will not correct cobalamin malabsorption due to other causes. For the test to give valid results, the kidney function should be normal.

In patients with pernicious anemia antibodies to intrinsic factor and parietal cell can be detected in the gastric juice as well as in blood.

Radiological examination of the digestive tract can diagnose conditions like tropical sprue, crohn′s disease, blind loops, diverticuli and ileocecal tuberculosis - all of which can lead to malabsorption of B12.

Endoscopy of the upper Gastrointestinal tract along with biopsy of the gastric mucosa is useful to diagnose atrophic gastritis.

DIFFERENTIAL DIAGNOSIS

In a typical case with isolated B12 or folate deficiency the clinical picture and few investigations would be enough to arrive at a diagnosis. However certain other conditions can mimic some of the clinical and laboratory features of B12 and folate deficiency and hence should be remembered to avoid error in diagnosis. For eg: macrocytosis which is a feature of megaloblastic anemia can also occur in conditions like aplastic anemia, alcoholism, hypothyroidism etc.

Bone marrow findings suggestive of severe megaloblastic anemia can also be present in myelodysplasia.

In any patient of peripheral neuropathy or non compressive myelopathy B12 deficiency should be ruled out, since if the folate status is normal, there may not be much hemato-logical abnormality, inspite of gross neurological involvement.

TREATMENT

Folate deficiency is treated by giving folic acid orally at 1 to 5 mg daily. Parenteral preparation containing 5mg/ml of folate is also available and should be used in patients with malabsorption. Pregnant women should be given 400 ìg of folate per day.

Therapeutic doses of folate will correct the hematologic abnormalities due to cobalamin deficiency also but the neurologic abnormalities can worsen and hence when the it is not known whether anemia is due to B12 or folate deficiency and the treatment is urgent, it is best to give B12 first or both B12 and folate but never folate alone.

B12 deficiency is usually treated by parenteral administration of B12. The treatment schedule consists of giving 1000ìg cobalamin intramuscularly daily for 10 - 14 days follwed by 1000 ìg once a week till hematocrit becomes normal followed by 1000 ìg once a month for life in patients with pernicious anemia or those with malabsorption.

Oral cobalamin is also available and is equally effective in correcting dietary cobalamin deficiency. However it cannot be given in patients with severe malabsorption.

Copyright 2004 - Indian Journal of Medical Sciences

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