Generality
Macrocytosis is a condition characterized by the presence, in peripheral blood, of numerous red blood cells (or erythrocytes) of greater than normal size.
Macrocytes can be found in small numbers even under normal conditions in the bloodstream, especially in newborns. However, a marked increase in these elements is indicative of some pathological processes, such as, for example, pernicious anemia and liver diseases .
The presence of macrocytes is found through a blood test, which assesses, in particular, the average corpuscular volume of red blood cells ( MCV ) and other erythrocyte indices .
The treatment of macrocytosis depends on the cause: if it is related to a deficiency of vitamin B12 or folic acid, for example, it is simply indicated the intake of supplements based on these elements and the correction of the diet.
What's this
Red blood cells: structure and dimensions
Red blood cells are blood cells that carry oxygen from the lungs to the tissues. In order for them to perform their function best, erythrocytes 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: the 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 : it is the opposite condition to the microcytosis, in which the erythrocytes have a diameter greater 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 exists when the average cell volume (MCV) is greater than 95 femtoliters.
What is Macrocytosis?
MACROCYTOSIS is the presence in the blood of macrocytes . This condition often occurs, but not necessarily, together with anemia .
Macrocytosis can be divided into two forms :
- MEGALOBLASTIC : the presence of macrocytes in the blood is due to a defect in the maturation of erythroid precursors, which prevents the terminal differentiation of erythrocytes. As a result, these elements accumulate in the bone marrow, resulting in megaloblastosis. Examples: pernicious anemia, folate deficiency anemia, etc .;
- NON MEGALOBLASTICA : at the medullary level, a defect in the production of red blood cells is not observed.
In a framework of macrocytosis, the pathological reduction of the hemoglobin content configures a state of MACROCYTIC ANEMIA .
Macrocytic anemia
Macrocytic anemia is a blood disorder characterized by an abnormal increase in the average corpuscular volume of red blood cells (MCV). In this context, in addition to 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.
Causes
Macrocytosis is found in association with various hematological and non-hematological diseases. Usually, the appearance of a population of macrocytic erythrocytes is an indication of ineffective hematopoiesis, especially with regard to the red blood cell line. Although the initial alterations may be minimal, this involves the release of larger elements into the circle.
Macrocytosis is found more frequently due to deficiency or defective use of vitamin B12 or folate .
Folate deficiency or vitamin B12 (cobalamin)
Folate and vitamin B12 are essential for the correct synthesis of red blood cells.
Their lack may result from:
- Reduced dietary intake;
- Decreased absorption;
- Increased requirements;
- Pharmacological therapies;
- Inborn errors of metabolism.
The presence of macrocytes in the blood is often indicative of some forms of anemia, such as megaloblastic and sideroblastic. Macrocytosis may depend on increased bone marrow synthesis following hemolysis or high blood loss ( haemorrhage ).
The increase in macrocytes in the bloodstream is also found in some acute leukemia, liver disease and post-splenectomy pictures . Other causes include the intake of drugs (usually antitumor and immunosuppressants) that interfere with DNA synthesis and, with a decidedly lower frequency, some metabolic disorders (such as hereditary orotic aciduria).
Rarely, then, erythrocytes can be larger due to the presence of congenital anomalies in the synthesis of DNA capable of interfering with erythropoiesis, ie in the formation of blood cells (eg dyseritropoietic syndrome).
Some cases of macrocytosis have an unknown aetiology .
Macrocytosis: main causes
The most frequent causes of macrocytosis are:
- Folate deficiency anemia;
- Vitamin B12 deficiency anemia (or pernicious anemia);
- Hemolytic anemias, which cause the destruction of red blood cells;
- Alcohol abuse (or chronic alcoholism);
- Hypothyroidism;
- Myelodysplastic syndrome.
Macrocytosis may also depend on:
- Aplastic anemia;
- Megaloblastic anemia;
- Spherocytosis;
- Hemolysis;
- Hemorrhage;
- Liver disorders (eg cirrhosis);
- Gastroenteritis, malabsorption syndromes and other pathologies of the gastrointestinal tract (eg Crohn's disease or celiac disease);
- Chronic obstructive disorders of the respiratory system (eg COPD);
- splenectomy;
- Myeloproliferative disorders (eg myelofibrosis, thrombocythemia and polycythemia vera);
- Chronic exposure to benzene;
- Tumor disorders and metastases;
- Severe hyperglycemia;
- Tropical sprue;
- Tobacco smoke habit;
- Down syndrome;
- Pregnancy.
Symptoms and Complications
Macrocytosis involves very variable clinical pictures, related to the 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.
Depending on the cause that determined it, macrocytosis takes on particular characteristics both in symptoms and in the values found with laboratory analyzes.
In most cases, they manifest themselves:
- Skin pallor (accentuated especially at face level);
- Fatigue and weakness;
- Fragility of nails and hair;
- Loss of appetite;
- Headache;
- Shortness of breath;
- Dizziness.
If they last for a few weeks, without ever regressing, these symptoms are indicative of the presence of macrocytic anemia.
In the most severe cases, macrocytosis can be associated with:
- 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.
Diagnosis
Macrocytosis 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 macrocytosis is transient or not and what is the root cause of the problem.
After collecting the anamnestic information, the general practitioner prescribes a series of laboratory investigations, with the aim of evaluating:
- Number and volume of red blood cells;
- Quantity and type of hemoglobin;
- State of body iron.
For a better characterization of the macrocytosis, therefore, 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 macrocytic anemia;
- Erythrocyte indices : they provide useful information regarding the size of red blood cells (normocytic, microcytic or macrocytic anemias) and the quantity 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 hemoglobin concentration 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;
- Serum iron, TIBC and serum ferritin;
- Bilirubin and LDH;
- Indices of inflammation, including C-reactive protein.
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 cause of the macrocytosis. Rarely, examination of a sample from the bone marrow may be necessary.
MCV: values of macrocytosis
As part of a complete blood count, the analysis of the MCV allows to know the "quality" of the red blood cells.
MCV is the abbreviation of " Mean Cell Volume " or " Mean Corpuscular Volume ". This acronym is used to indicate the average corpuscular volume, ie the average volume of red blood cells . In essence, the MCV lets you know if the erythrocytes are too small, too large or simply normal.
The MCV is, therefore, the most useful index to highlight a macrocytosis and is obtained by dividing the hematocrit by the number of red blood cells.
This parameter also allows to classify the type of anemia according to the morphology of the red blood cells:
- Microcytic anemias : MCV <80 fl *.
- Normocytic anemias : MCV = 80-95 fl; any normocytic anemias may be due to acute bleeding or hemolysis (destruction of red blood cells).
- Macrocytic anemias : MCV> 95 fl; the presence of macrocytes may be due to myelodysplasia, reticulocytosis, hypothyroidism, liver disease (liver disease, such as cirrhosis) and alcoholism.
* fl (femtolitri) is the unit of measurement of the average cell volume and is equivalent to 0.000001 billionths of a liter (0.000000000000001 liters); the MCV can also be expressed in cubic micrometers or µm3. It should be remembered, in fact, that a liter is equivalent to a cubic decimeter, a milliliter to a cubic centimeter, a microliter to a cubic millimeter and so on.
It should be noted that the MCV reference value may vary slightly from laboratory to laboratory. Therefore, when it is necessary to establish with greater precision the pathological significance of macrocytosis or another alteration of MCV, it is useful to cross this value with other parameters, such as the number of red blood cells (RBC), the average content of hemoglobin for each red blood cell (MCH) and the average concentration of hemoglobin within a red blood cell (MCHC, apparently similar to the previous one, but very important, since it gives an indication of the relationship between the volume of red blood cells and their hemoglobin content ).
The value of MCV is of clinical importance even when interpreted in the light of another blood parameter: RDW. The latter provides information on the distribution of red blood cells and allows, among other things, the distinction between hypoproliferative anemia (characterized by the presence of reticulocytes, ie immature erythrocytes) and haemolytic anemia (due to an increase in the destruction of the corpuscles red).
Treatment and Remedies
The treatment of macrocytosis varies according to the cause: the treatment of the responsible pathologies improves the symptoms and usually determines the resolution of the clinical condition. It should be noted, however, that some hereditary forms of macrocytosis are congenital, therefore they are not curable.
Possible interventions
In the presence of mild and transient forms, macrocytosis does not compromise quality of life and no special measures are required. However, some forethought may be useful.
Generally speaking, your doctor may recommend that you take vitamin B12 and folate supplements orally to increase normocyte production. In cases of pernicious 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 more serious cases, however, the management of macrocytosis 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.
