Generality
Megaloblastic anemia is a haematological disease characterized by the presence of megaloblasts in the bone marrow and in peripheral blood. In erythropoiesis (line of differentiation and maturation of the red blood series), megaloblasts are large erythroid precursors .
A marked increase ( megaloblastosis ) is indicative of an altered DNA synthesis, classically secondary to a deficiency of vitamin B12 or folic acid . Both of these substances are necessary for the production of red blood cells and their deficiency causes a maturational defect of these elements (in particular, the cytoplasm is excessive with respect to the nucleus). As a result, these elements accumulate in the bone marrow, resulting in megaloblastosis, while in peripheral blood, macrocytosis occurs, with red blood cells (or erythrocytes) of greater magnitude than the norm.
The clinical picture of megaloblastic anemia can also be supported by numerous other pathological conditions, congenital or acquired, accumulated by a defect in the maturation of erythroid precursors, which prevents the terminal differentiation of erythrocytes.
Megaloblastic anemia is diagnosed by a blood test, aimed at assessing, in particular, the average corpuscular volume of red blood cells ( MCV ) and other erythrocyte indices .
The treatment of megaloblastic anemia always depends on the cause: if the hematological picture is related to a deficiency of vitamin B12 or folic acid, the intake of supplements based on these elements and the correction of the diet is indicated .
What's this
Megaloblasti: what are they?
Megaloblasts are the progenitor cells of the elements of the red blood series. These elements are usually present in the bone marrow and are so called because of their large size.
What is Megaloblastic Anemia?
Megaloblastic anemia includes a heterogeneous group of diseases characterized by the presence of megaloblasts (immature progenitor cells of the macrocytes) and macrocytes (red blood cells larger than normal, between 9-12 µm) in the blood.
Megaloblastic anemia is due to a defect in the maturation of erythroid precursors (the so-called red blood series), which prevents the terminal differentiation of erythrocytes. As a result, these elements accumulate in the bone marrow, resulting in a condition of megaloblastosis .
In summary, the hematological picture of megaloblastic anemia is characterized by:
- Macrocytes in peripheral blood (in the circulation, megalocytes can also be found, ie red blood cells with a diameter greater than 14 µm) -> Macrocytosis
- Excessive megaloblasts in the bone marrow -> Megaloblastosis
Red blood cells: key points
To address this pathology correctly, it is necessary to briefly recall some key points about the structure and normal size of RED GLOBULES (or erythrocytes ).
- Red blood cells are blood cells that carry oxygen from the lungs to the tissues. In order for them to perform their function best, they must have the shape of a biconcave disk, with a flattened core and adequate dimensions. When they are larger than normal, erythrocytes are called macrocytes (or megalocytes ).
In detail, based on the size of the erythrocytes it is possible to distinguish:
- Normocytosis : red blood cells are of normal size, ie they have a diameter equal to 7-8 micrometers (µm).
- Microcytosis : it is characterized by microcytic erythrocytes, ie smaller than the norm;
- Macrocytosis : is the condition opposite to the microcytosis, in which the erythrocytes have a larger diameter than normal, between 9-12 µm. Megalocytes are red blood cells even larger than macrocytes (diameter greater than 14 µm).
The physical characteristics of red blood cells are defined by red cell indices . In the laboratory analysis, the most useful blood chemistry parameter to determine if red blood cells are normal, too large or too small, is the mean corpuscular volume ( MCV ). By definition, macrocytosis (ie presence in the blood of macrocytes ) exists when the average cell volume (MCV) is greater than 95 femtoliters (fL) ; in megaloblastic anemia, this parameter is included or even greater than the range between 100 and 150 fL.
Causes and Risk Factors
Megaloblastic anemia is sustained by the deficiency or incorrect use of vitamin B12 or folate, but numerous conditions, congenital or acquired, united by defects of purine or pyrimidine synthesis, can determine this hematological picture.
Megaloblastic anemia is therefore indicative of ineffective hematopoiesis regarding the cell line of red blood cells and, in particular, is characterized by a delay in DNA synthesis .
This involves a nucleocytoplasmic matrix asynchrony of the erythroid precursors (from the proeritroblast to the reticulocyte), that is the cells of the bone marrow from which the red blood cells derive have increased dimensions, with an excessive cytoplasm with respect to the nucleus.
In the bone marrow, therefore, an ineffective cytogenesis and early cell death are observed, so in megaloblastic anemias the erythroid cells produced at bone level are largely destroyed, without being able to reach the circulatory stream. With blood counts, it is found in association with macrocytic anemia .
Megaloblastic anemia: what are the causes?
Classically, the causes of megaloblastic anemia are divided into two large groups, based on the deficient factor responsible for the hematological picture, ie:
- Folate deficiency anemia ;
- Vitamin B12 deficiency anemias (cobalamin) ;
In some cases, however, the vitamin deficiency is mixed. Folate and vitamin B12 are fundamental for the correct synthesis of red blood cells, especially when there is a rapid turnover (as in the marrow) and in the gastrointestinal tract; their deficit may result from:
- Poor or poorly balanced diet (reduced intake of folic acid and vitamin B12):
- Alcohol abuse (or chronic alcoholism)
- Malnutrition
- Vegetarian diet
- Faulty absorption for gastric or intestinal causes
- Gastroenteritis, malabsorption syndromes and other diseases of the gastrointestinal tract, including Crohn's disease and celiac disease
- Tropical sprue
- Gastrectomy and resections of the small intestine
- Hypothyroidism
- Scleroderma
- Use of drugs (antimetabolites)
- Folate antagonists, such as dihydrofolate reductase inhibitors, antiepileptics, sulfonamides, methotrexate and nitrous oxide
- Drugs that interfere with DNA synthesis (antiblastic, azathioprine, thioguanine)
- Contraceptive therapy
- Proton pump inhibitors, H2 receptor antagonists and biguanides
- Increased requirements
- Pregnancy
- Dialysis
- Chronic hemolysis and various hematological diseases
- Cardiac and renal insufficiency
- Neoplasms
- Hyperthyroidism
- Inborn errors of metabolism
- Transcobalamin II deficiency
Did you know that…
When an anesthesia is administered with nitrous oxide, acute megaloblastic anemia can occur.
Symptoms and Complications
Megaloblastic anemia is characterized by an abnormal increase in the average corpuscular volume of red blood cells (MCV). In this context, in addition to the finding of megaloblastosis and macrocytosis, the average concentration of hemoglobin (Hb) contained within the red blood cells is lower than the norm; the result is a reduced ability of the blood to carry oxygen.
Megaloblastic anemia involves variable clinical pictures, related to the specific cause from which it derives: in some cases, the disorder is almost asymptomatic; other times, the condition is incapacitating or puts the life of the sufferer at risk.
Megaloblastic anemia can manifest itself with:
- Skin pallor (accentuated especially at face level);
- Fatigue and weakness;
- Fragility of nails and hair;
- Loss of appetite;
- Headache;
- Shortness of breath;
- Dizziness;
- Palpitations;
- Stunning;
- Chest pains;
- Jaundice;
- Blood loss and bleeding tendency;
- Recurrent fever attacks;
- Irritability;
- Progressive distension of the abdomen (secondary to splenomegaly and hepatomegaly);
- Hypoxia;
- Hypotension;
- Heart and lung problems;
- Neurological damage.
Did you know that…
Vitamin B12 deficiency leads to a specific type of anemia called " pernicious ". Pernicious anemia is, therefore, a type of megaloblastic anemia of autoimmune etiology.
Diagnosis
How is the diagnosis of Megaloblastic Anemia formulated?
Megaloblastic anemia is found with blood tests and can be suspected due to the presence of suggestive symptoms . Sometimes, however, the response can occur in a completely random way, as the patient is asymptomatic. In this case it is advisable to consult a doctor to assess whether the megaloblastic anemia is transient or not and what is the root cause of the problem.
After collecting the anamnestic information, for a better characterization of megaloblastic anemia, it is useful to perform the following blood tests :
- Complete blood count:
- Red blood cell count (RBC) : erythrocyte count is generally but not necessarily decreased in megaloblastic anemia;
- Red cell indexes : these parameters provide useful information regarding the size of red blood cells (normocytic, microcytic or macrocytic anemias) and the amount of Hb contained within them (normochromic or hypochromic anemias). The main erythrocyte indices are: Medium Corpuscular Volume ( MCV, used to establish the average size of red blood cells), Medium Corpuscular Hemoglobin ( MCH ) and Medium Corpuscular Hemoglobin Concentration ( MCHC, coincides with the concentration of hemoglobin in a single red blood cell);
- Reticulocyte count : quantifies the number of young (immature) red blood cells present in peripheral blood;
- Platelets, leukocytes and leukocyte formula ;
- Hematocrit (Hct) : percentage of the total volume of blood made up of red blood cells;
- Amount of hemoglobin (Hb) in the blood;
- Red cell size variability (amplitude of red blood cell distribution or RDW, from the English "Red Cell Distribution Width").
- Microscopic examination of the erythrocytic morphology and, more generally, of the peripheral blood smear;
- Search for antibodies against parietal stomach or anti-intrinsic factor cells;
- Serum iron, TIBC and serum ferritin;
- Bilirubin and LDH;
- Indices of inflammation, including C-reactive protein;
- Evaluation of gastric pH;
- Endoscopy of the gastric mucosa;
- Schilling test.
Any anomalies found during the definition of these parameters can alert laboratory personnel to the presence of anomalies in the red blood cells; the blood sample could be subjected to further analysis to identify the exact reason of megaloblastic anemia in the patient. In some cases, it may be necessary to examine a sample taken from the bone marrow (bone marrow biopsy). Contemporary iron deficiency or minor thalassemia may mask macrocytosis.
Treatment
The treatment of megaloblastic anemia varies depending on the cause: the management of the responsible conditions improves the symptoms and usually determines the resolution of the clinical picture. It should be noted, however, that some hereditary forms of megaloblastic anemia are congenital, therefore they are not curable.
Generally speaking, your doctor may recommend that you take vitamin B12 and folate supplements orally to increase normocyte production. In cases of megaloblastic anemia in which an inflammatory state of the gastric membrane is present, the use of immunosuppressants and high-dose corticosteroids may also be indicated.
In the most serious cases, however, the management of megaloblastic anemia may include:
- Blood transfusions to make up for the lack of normal red blood cells and to avoid complications such as heart failure;
- Bone marrow or stem cell transplant from compatible donors.
In addition to specific therapies, great importance is given to regularly practiced physical activity and the adoption of a healthy and balanced diet.
