Anemia is a type of blood disorder where the number of red blood cells (RBCs) in the blood is lower than normal. Megaloblastic anemia, on the other hand, is a type of anemia that is characterized by larger than normal red blood cells (megaloblasts) and not having enough of them. When the red blood cells (RBCs) in the blood are not properly produced, megaloblastic anemia occurs. The bone marrow is a soft spongy material inside the bones, which produces the primary blood cells of the body. The cells produced in the bone marrow are the red blood cells (RBCs), white blood cells (WBCs), and platelets. The red blood cells (RBCs) are discharged from the bone marrow to the bloodstream where the cells travel and deliver oxygen to the body's tissues. Since the red blood cells (RBCs) are too big in megaloblastic anemia, they may not be able to go out of the bone marrow and be released into the bloodstream and transport oxygen.
Although megaloblastic anemia can affect any individual of ethnic and racial background, this type of anemia is frequently seen in countries where malnutrition is extensive and regular vitamin supplementation for pregnant women and elderly individuals is not available. Men and women are equally affected by this condition.
Megaloblastic Anemia Symptoms
Most cases of megaloblastic anemia gradually develop. That is why many people who have this condition could not experience any symptoms for several years.
The common symptoms of megaloblastic anemia are:
- Shortness of breath
- Abnormal paleness of the skin
- Tender or smooth tongue
- Numbness in extremities
- Muscle weakness
- Weight loss
- Swollen tongue (glossitis)
- Fast heartbeat
- Tingling in hands and feet
- Body aches and pain
- Difficulty in breathing
The symptoms on the list above could differ from person-to-person. Other people with megaloblastic anemia could also experience gastrointestinal abnormalities such as diarrhea, loss of appetite, and nausea. Hepatomegaly or mild enlargement of the liver and a slight yellowing of the eyes or skin could also occur.
A megaloblastic anemia caused by vitamin B12 deficiency could develop neurological symptoms. Tingling and numbness in the hands and feet may be felt initially. Over time, vision loss, problems with gait or balance, memory loss, and mental confusion develop. Panic attacks, depression, listlessness, and insomnia were also reported in people with vitamin B12 deficiency.
Megaloblastic Anemia Causes
The most common causes of megaloblastic anemia are folate and vitamin B12 deficiency. Both folate and vitamin B12 act as building blocks and are the nutrients that are necessary for the production of healthy red blood cells (RBCs). Inadequate folate and vitamin B12 in the body can affect the makeup of red blood cells (RBCs). As a result, the red blood cells (RBCs) produced will not divide and will not be able to reproduce the way they should. Moreover, without these vitamins, the synthesis of deoxyribonucleic acid (DNA) is hampered.
1) Folate Deficiency
Folate is a nutrient that is important for the normal development of red blood cells (RBCs). It is found in foods such as beef liver, Brussels sprouts, and spinach. Oftentimes, folate is mixed up with folic acid, an artificial type of folate found in supplements.
A deficiency in folate can be caused by not consuming a healthy and proper diet. Chronic alcohol abuse can also cause folate deficiency as alcohol hinders the body’s ability to absorb folic acid. Folate deficiency is commonly seen in pregnant women because the fetus needs a great amount of folate for its development. People who are undergoing hemodialysis and people with chronic hemolytic anemias also require high demands of folate. Thus, failure to have enough supply of folate in the body can potentially lead to folate deficiency.
2) Vitamin B12 Deficiency
Vitamin B12 deficiency is commonly caused by not having enough protein in the stomach. This protein is called as the "intrinsic factor". Without this protein, vitamin B12 cannot be absorbed no matter how much a person eats. Not having enough vitamin B12 in one's diet can also cause vitamin B12 deficiency.
Vitamin B12 can be found in foods such as meat, eggs, milk, and fish. In some cases, people cannot absorb enough of this nutrient from the foods they eat, which leads to the development of megaloblastic anemia. A megaloblastic anemia that is caused by vitamin B12 deficiency is called as "pernicious anemia".
Aside from folate and vitamin B12 deficiencies, the other causes of megaloblastic anemia are direct interference of DNA synthesis through HIV infections, myelodysplastic disorders, and certain medications. For instance, the drugs used for the treatment of cancer can impair the body's ability to absorb folate.
In some cases, there is an unknown cause for the occurrence of megaloblastic anemia.
Megaloblastic Anemia Treatment
The type of treatment a person receives for megaloblastic anemia depends on its cause. The treatment may also depend on the overall health and age of the person. Response to treatment and the severity of the disease can also come into play.
A megaloblastic anemia that is caused by folate deficiency can be treated with intravenous or oral folic acid supplements. Changes in the diet can also boost the level of folate in the body. Folate-rich foods such as oranges, peanuts, enriched grains, green leafy vegetables, and lentils can be included in the diet.
For a megaloblastic anemia caused by vitamin B12 deficiency, monthly injections of vitamin B12 may be needed. Oral supplements may also be advised. Foods that can increase the level of vitamin B12 in the body include chicken, red meat particularly beef, shellfish, eggs, fortified cereals, and milk. These foods must be added to your diet to avoid a deficiency of vitamin B12. Immediate treatment of vitamin B12 deficiency is essential because of the neurological risks.
For people who cannot absorb folate and vitamin B12 properly, a life-long supplementation of these nutrients is needed.
If there are underlying diseases such as tropical sprue, blind loop syndrome, Crohn’s disease, celiac disease, or inborn errors of metabolism that cause these deficiencies, proper treatment for the specific disease must be addressed first. Folate or vitamin B12 supplementation may also be required.
If the cause of megaloblastic anemia is due to the use of certain medications, then stopping such drugs or lowering their dosage must be done. For people who needs higher than normal folate, preventive folate supplementation is recommended.
Presence of Hypersegmented Neutrophils in Megaloblastic Anemia
There are only three or four lobes seen in healthy neutrophils. Hypersegmented neutrophils are a clinical laboratory finding where the neutrophils abnormally show six or more lobes.
In megaloblastic anemia, the cells rapidly divide in the bone marrow affecting the synthesis of DNA. There are hypersegmented neutrophils present in megaloblastic anemia because folate and vitamin B12 are required for the normal production of DNA. Therefore, the cells become larger since the cytoplasm does not get a signal to cease its maturation. In other words, the cell grows bigger before the nucleus gets to be matured enough to indicate division, making the cells larger than normal with multi-segmentation of neutrophils. The presence of hypersegmented neutrophils in megaloblastic anemia could also be due to the abnormal, asynchronous maturation that is going on in the neutrophil series.
Non-megaloblastic anemia simply represents macrocytic anemias where the DNA synthesis is not impaired. Oftentimes, they are normocytic but are occasionally macrocytic. If macrocytosis is seen, it is usually mild. The causes of non-megaloblastic anemia are not associated with the defective creation of DNA.
Non-megaloblastic anemia is less common compared to megaloblastic anemia. This condition is characterized by the presence of mature but huge red blood cells (RBCs) and the absence of megaloblasts. This kind of red blood cells (RBCs) is usually seen in newborns only.
Causes of non-megaloblastic anemia include:
- Liver disease
- Chronic alcoholism
- Blood disorders such as red cell aplasia, myelodysplastic syndromes, myeloid leukemia, and aplastic anemia
- Drugs such as azathioprine
Non-megaloblastic anemia is comprised of disorders that are characterized by an increased number of reticulocytes as well as those where the reticulocytes are normal or reduced in number. Non-megaloblastic anemia was most often related to liver disease and alcoholism or with hemolytic anemia. In some cases, non-megaloblastic anemia was observed in patients with a variety of refractory anemias.
Non-megaloblastic anemia is suspected in individuals with macrocytic anemias if testing excludes folate and vitamin B12 deficiencies as well as reticulocytosis. If non-megaloblastic anemia is clinically unclear, cytogenic analysis and bone marrow examination are done to rule out myelodysplasia. The bone marrow in non-megaloblastic anemia is not megaloblastic.
Types of Megaloblastic Anemia
1) Folate-Deficiency Anemia
It is a type of megaloblastic anemia where the reduced number of red blood cells (RBCs) is due to the lack of folate. The condition also shows abnormally big red blood cells (RBCs). Folate-deficiency anemia is due to alcoholism, poor diet, eating overcooked food, and pregnancy. Symptoms of this condition include fatigue, pallor, sore mouth and tongue, decreased appetite, diarrhea, lack of energy, being grouchy, and headaches. This type of megaloblastic anemia is usually diagnosed after a doctor performs a physical exam and takes your medical history. Blood tests are also done to confirm the diagnosis.
2) Pernicious Anemia
Pernicious anemia is due to body's inability to absorb vitamin B12, which is needed for the production of enough red blood cells (RBCs). Although it was once considered as a deadly disorder, it is still regarded as a rare condition since it only affects 0.1% of the general population. The common symptoms of pernicious anemia are weakness, chest pain, headaches, and weight loss. Lack of vitamin B12 and intrinsic factor are some of the causes of this disease. The risk factors for the development of pernicious anemia include a family history of the disease, type 1 diabetes, being 60 years old and above, not taking B12 supplements, being strictly vegetarian, and being a Scandinavian or Northern European descent.
3) Megaloblastic Anemia and Vitamin B12
The body needs vitamin B12 to make healthy red blood cells (RBCs). Meat, shellfish, dairy products, poultry, and eggs are good sources of vitamin B12. The body must also be able to absorb enough of this nutrient, and the intrinsic factor released in the stomach can help the body do this. When there is not enough vitamin B12, the body is at risk of developing abnormally large red blood cells (RBCs) in the bone marrow. When this occurs, it could lead to the development of megaloblastic anemia.
Pathophysiology of Megaloblastic Anemia
Megaloblastic anemia is due to a variety of DNA synthesis defects.
In the case of folate deficiency, purine biosynthesis is affected as folic acid is important in this process. Folic acid is vital for purine biosynthesis. Folic acid absorbed from the diet must be stimulated to create an active tetrahydrofolic acid (THF). Tetrahydrofolic acid is essential for single-carbon transfers in the production of pyrimidine nucleotides. Without sufficient levels of biologically active tetrahydrofolic acid, the capability to fix and reproduce DNA is reduced. Vitamin B12 is a cofactor for the activation of folic acid in a pace that also converts homocysteine to methionine.
Tetrahydrofolic acid production is diminished and slowed DNA synthesis is seen in the case of not enough folic acid intake. The effect on hematopoiesis is to lessen the speed of cell production, which results to pancytopenia (reduced number of RBCs, WBCs, and platelets). In the cells that are synthesized, the effect made is an arrest of nuclear maturation. In other words, the cells that have been created have immature nuclei compared with the degree of maturation of the cytoplasm.