What Is Normocytic Anemia

Overview

Anaemia is one of the most common diseases that can be detected through a complete blood count (CBC), and most people have heard of it. But what exactly is anaemia?

Anaemia is a deficiency in red blood cells (RBC) that can either decrease the overall number of cells, decrease their size, or decrease the proportion of red blood cells to blood volume (hematocrit)¹. When one or multiple of these factors are affected, they can impair the body’s ability to transport oxygen from your lungs to other tissues, resulting in anaemia.¹ In the case of normocytic anaemia, the word “normocytic” means that the RBCs are of normal size, and there’s either a decrease in the overall number of cells being produced or these cells are being lost or destructed.¹ Normocytic anaemia is usually caused by haemorrhage (blood loss), infection or chronic diseases.¹

Although it can often be a silent disease, anaemia can produce signs and symptoms that one should look out for, and there are ways to prevent it. Keep on reading to understand more about normocytic anaemia.

Causes

The World Health Organization (WHO) defines anaemia as an overall decrease in the number of red blood cells or an impairment in their ability to transport oxygen.² RBCs are capable of transporting oxygen through a molecule inside them known as haemoglobin, that contains iron, so defects that impair haemoglobin production or iron deficiency can also cause anaemia.¹

The anaemic disorders are classified primarily through the size of the erythrocytes (red blood cells):²

• Microcytic anaemia is the one in which the diameter (size) of the red blood cells is diminished; it is the most common form of anaemia, and its main cause is iron defficiency.² However, other possible causes for microcytic anaemia are chronic diseases, thalassemia, sideroblastic anaemia (a defect in the shape of the cells), and diseases that affect haemoglobin production.²

• Macrocytic anaemia is the opposite, as the diameter of the erythrocytes is augmented; it is commonly divided into megaloblastic and non-megaloblastic anaemia.²
  • Megaloblastic anaemia is characterised by alterations in other types of blood cells, including white blood cells (WBC) like neutrophils, caused by DNA mutations.² Vitamin B12 deficiency, folate deficiency, and the use of drugs that affect DNA synthesis like cytarabine and azidothymidine (AZT) are common causes of megaloblastic anaemia.²
  • Non-megaloblastic anaemia lacks these genetic alterations, affecting only RBCs.² Chronic use of alcohol, liver failure, hypothyroidism, myelodysplastic syndrome (MDS), and haemolysis (blood destruction) are causes of non-megaloblastic anaemia.²

• Normocytic anaemia is characterised by a normal diameter of the red blood cells (RBC).² It is sometimes called normochromic normocytic anaemia.² Acute forms of normocytic anaemia are often caused by blood loss.² Chronic forms, however, have been associated with chronic diseases and infections, and this form of anaemia has been called “anaemia of chronic disease” (ACD) as well.² Causes of normocytic anaemia include:
  • Chronic infection:
    • Osteomyelitis²
    • Bacterial endocarditis²
    • Tuberculosis²
    • Abscesses²
    • Chronic urinary tract infections²
  • Chronic inflammatory disorders:
    • Rheumatoid arthritis²
    • Polymyalgia rheumatica²
    • Systemic lupus erythematosus²
    • Inflammatory bowel disease²
  • Metastatic disease (related to cancer)²
  • Renal failure¹
  • Endocrine failure: hypothyroidism and/or hypopituitarism¹
  • Bone marrow failure: pure red-cell aplasia, aplastic anaemia, infiltration¹
  • Heart disease: both congestive cardiac failure and ischaemic heart disease have been linked to normocytic anaemia²
  • Age: individuals over the age of 85 years are more commonly affected²

Chronic anaemia is often caused by a secondary cause, instead of bone marrow failure.¹ In most cases, it can be related to three mechanisms:

• Increase in pro-inflammatory cytokines and iron dysregulation: there is a molecule known as hepcidin that regulates iron levels in the blood; an increase in hepcidin can lead to iron being trapped inside cells (mostly liver, intestines and white blood cells), instead of circulating freely in the blood to transport oxygen as needed Inflammation can lead to an increase of interleukin 6 (IL-6), a cytokine (mediator molecule) that increases hepcidin levels, thus decreasing iron concentration in blood.³
• Lack of erythropoietin (EPO) or diminished response to EPO: chronic diseases, especially kidney disorders, can diminish the production of erythropoietin, a molecule present in the bone marrow that assists the production of red blood cells.¹ Without EPO, fewer erythrocytes are produced, leading to anaemia.¹
• Decreased RBC survival: in some cases, red blood cells die prematurely and the body cannot replenish them fast enough to prevent anaemia.³ This is known as hemolytic anaemia because the cells are being destroyed prematurely.³ Genetic defects and hypersplenism (augmented function of the spleen) can cause this form of anaemia.¹

Signs and symptoms

There are a few signs and symptoms that can point to anaemia.¹ A few of them are:

• Fatigue⁴
• Dizziness⁴
• Dyspnea (difficulty breathing)⁴
• Weakness⁴
• Headaches⁴
• Decreased concentration¹

Acute forms of anaemia, often caused by blood loss, can lead to different symptoms: confusion, lightheadedness, loss of consciousness, and polydipsia (increased thirst) can be signs of haemorrage.⁴ Blood loss severe enough to cause symptoms should be taken seriously and it requires immediate medical attention, as it can be potentially fatal.

Diagnosis

Diagnosis is made through clinical evaluation and a complete blood count (CBC)¹.

During the physical examination, a medical professional should look for pallor of the skin, conjunctivae, lips, palmar creases, and nail beds.¹ Other signs that are important are postural hypotension, jaundice, bone pain, and splenomegaly (augmented spleen).¹

Questions about the patient’s diet, use of medication, history of diseases (especially chronic diseases or inflammatory conditions), blood loss (through urine, stool, menstruation or other means), and family history of blood conditions like thalassemia or sickle-cell disease are also important in determining the origin of the anaemia.¹

A complete blood count (CBC) can prove anaemia and determine its type accurately.¹ A few important points in a CBC are:

• RBC count (total number of red blood cells)⁵
• Haemoglobin count (the amount of haemoglobin present in one’s blood)⁵
• Hematocrit (the fraction of RBC in blood)⁵
• Mean red blood cell volume (MCV)⁵
• Mean haemoglobin amount per red blood cell (MCH)⁵
• Mean amount of haemoglobin relative to the size of the cell (haemoglobin concentration) per red blood cell (MCHC)⁵
• Red blood cell distribution width (RWD)¹

A combination of these factors can specify which type of anaemia a person has.⁵ Someone who has a normal RBC count but a decreased mean RBC volume has microcytic anaemia; another person who has a normal mean RBC volume but a diminished amount of haemoglobin per RBC could have a hypochromic anaemia (often caused by iron deficiency); on the other hand, someone who has overall normal values but a decreased RBC count and decreased hematocrit could suffer from blood loss or hemolytic anaemia.

If there is suspicion of an underlying cause of anaemia, a physician might request other exams to determine its cause.

Management and treatment

Anaemia induced by blood loss is easily treated by identifying the cause and stopping the haemorrage.¹ Blood transfusions and IV fluids might be necessary depending on the volume lost.¹

As most cases of normocytic anaemia are related to chronic diseases, treating them is the best course of action to solve anaemia.¹ Sometimes, erythropoiesis-stimulating agents, blood transfusions and iron supplementation can be options to treat severe cases of anaemia while simultaneously treating the underlying condition; in the case of patients with normal EPO levels, erythropoiesis-stimulating agents are not effective.¹ Iron supplementation should be considered only if iron levels are below average, as excessive iron intake can have consequences such as liver necrosis, seizures, cardiogenic shock, and coma.¹

If the anaemia is being caused by a medication, this medication should be substituted if possible.¹ It is known that some drugs like cytarabine and AZT can cause anaemia, but even though they are necessary to the patient, alternatives should be considered if feasible.²

Bone marrow transplant is an option if the anaemia is caused by aplasia or bone marrow defects.¹

Summary

Normocytic anaemia is a type of anaemia (a disease in which there are less red blood cells than ideal, or in which the red blood cell's ability to transport oxygen is impaired) in which RBCs are of normal sizes. 

Common causes of this disease include acute blood loss and destruction (hemolysis), chronic infections (like tuberculosis, osteomyelitis and bacterial endocarditis), chronic inflammatory diseases (like rheumatoid arthritis and lupus), heart disease, bone marrow defects and kidney disease. Signs and symptoms include fatigue, dizziness, difficulty breathing, weakness, and headaches, but acute cases of anaemia can lead to loss of consciousness and fainting. 

Diagnosis is made through a combination of physical examination, family history and a complete blood count, although in some cases more exams can be necessary to identify an underlying cause of the anaemia. Treatment consists of treating the underlying cause, if there is any, IV fluids, blood transfusions, and medication to stimulate the proliferation of red blood cells.