Mean corpuscular volume (MCV) is the average volume of red cells in a specimen. MCV is elevated or decreased in accordance with average red cell size; ie, low MCV indicates microcytic (small average RBC size), normal MCV indicates normocytic (normal average RBC size), and high MCV indicates macrocytic (large average RBC size).

The reference ranges for MCV are as follows:

Adult/elderly/child: 80-95 fL

Newborn: 96-108 fL

MCV, along with mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC), is a part of RBC indices (erythrocyte indices), which are measurements and/or calculations for determining the size, content, and haemoglobin concentration.

More recently, red cell distribution width (RDW) has also been included as a part of RBC indices. The indices are useful in the morphologic characterization of anaemia. Among these parameters, MCV is the most useful value used to classify the type of anaemia based on red cell morphology. Of note, type of anaemia can also be categorized based on bone marrow responses to anaemia using reticulocyte count into hypoproliferative anaemia (decreased red blood cell production) and hemolytic anaemia (increased red blood cell destruction).

Main types of anaemia classified based on red cell morphology and their common causes

The common causes of microcytic and hypochromic anaemia (decreased MCV and MCH) are as follows:

·                    Iron deficiency anaemia

·                    Anaemia of chronic disease

·                    Thalassemia

·                    Sideroblastic anaemia

The common causes of macrocytic anaemia (increased MCV) are as follows:

·                    Folate deficiency anaemia

·                    Vitamin B12 deficiency anaemia

·                    Liver disease

·                    Hemolytic anaemias

·                    Hypothyroidism

·                    Excessive alcohol intake

·                    Aplastic anaemia

·                    Myelodysplastic syndrome

The common causes of normocytic and normochromic anaemia (normal MCV) are as follows:

·                    Anaemia of chronic disease

·                    Acute blood loss

·                    Hemolytic anaemia, such as autoimmune hemolytic anaemia, hereditary spherocytosis, or nonspherocytic congenital hemolytic anaemia (G6PD deficiency, other)

·                    Anaemia of renal disease

·                    Aplastic anaemia

Of note, when considering the causes of anaemia, the guidelines above are helpful but have limitations. For example, hemolytic anaemia and aplastic anaemia can manifest as normochromic and normocytic anaemia or macrocytic anaemia; anaemia of chronic disease can be normochromic and normocytic anaemia or microcytic anaemia; sideroblastic anaemia can be microcytic anaemia, macrocytic anaemia, or normochromic and normocytic anaemia (due to the presence of a dimorphic population of microcytes and macrocytes).

In addition, once the causes of anaemia are considered, correlation with clinical findings, including history and physical examination, is important, as is, when necessary, performing more definitive tests to arrive with a definitive diagnosis.

Aetiology.

Clinicians can discern definitive diagnoses for the type of anaemia based on the MCV value.

Microcytic anaemia is a type of anaemia where the average erythrocyte is smaller than normal and much smaller than a leukocyte. On the complete blood count (CBC), its measure is under 80 fL while normal MCV is between 80 to 100 fL. It is commonly seen in chronic iron-deficient anaemia, anaemia of chronic disease, sideroblastic anaemia, and thalassemias but can also occur in other conditions. Microcytic cells can appear to have a larger area of central pallor, especially in the setting of iron-deficient anaemia and anaemia of chronic disease.

Macrocytic anaemia is a type of anaemia where the average red blood cell volume is larger than normal. On CBC, its MCV is over 100 fL. Macrocytic anaemia further subcategorizes as megaloblastic or non-megaloblastic. Megaloblastic anaemia is due to impaired DNA synthesis versus normal DNA synthesis in non-megaloblastic anaemia. Megaloblastic anaemia is commonly secondary to folate (also knowns as folic acid or vitamin B9) deficiency, cobalamin/vitamin B12 deficiency, and orotic aciduria, an autosomal recessive disorder that does not allow conversion of orotic acid to UMP.  Non-megaloblastic anaemia is due to hepatic insufficiency, chronic alcoholism, or a rare congenital disease Diamond-Blackfan anaemia.

Normocytic anaemia is anaemia with a low haemoglobin and hematocrit range but MCV in the normal range of 80 to 100 fL. This type of anaemia can subclassify as hemolytic and non-hemolytic. Normocytic hemolytic can occur intravascularly and extravascularly and can be due to myriad causes. Other laboratory values on the CBC will further indicate the type of anaemia.

Non-hemolytic normocytic anaemias can present in early anaemia of chronic disease, early iron deficiency anaemia, aplastic anaemia, microangiopathic hemolytic anaemias, and even certain plasmodial infections.

History and Physical.

There are many findings when it comes to anaemia presentation.

MCV below 80:

Iron deficiency anaemia presents with conjunctival pallor, fatigue, cold intolerance, and cold distal extremities, koilonychia, occasionally pica, glossitis, dry, cracked lips, and cheilosis. These patients will generally describe an event with chronic blood loss, chronic inflammation, exposure to lead paint, or a family history of thalassemias. Anaemia of chronic disease presents with the disease that is causing chronic inflammation such as arthritis in rheumatoid arthritis or malignancy. Also, these diseases can be asymptomatic. However, these patients may have a family history of cancer, autoimmune disease, or rheumatologic disease that can assist in the diagnosis.

Additionally, thalassemias can present with “chipmunk” facies due to bone marrow expansion and extramedullary hematopoiesis. This process can also present with hepatomegaly and splenomegaly on physical examination. An X-ray may display skeletal deformities. These patients will more than likely have a family history, including one or both of their parents. Patients with lead exposure are commonly exposed to lead paints, especially children in an older home consuming the lead-based paints. Adults are likely to report exposure through occupations such as miners, pipefitters, auto shop workers, and ceramic glazes. Lead poisoning can present with lead lines on the gums and on long bones metaphysis, abdominal pain, peripheral neuropathy, most commonly fibular and radial nerve neuropathies, and fatigue. Children can present with encephalopathy. Because sideroblastic anaemia can result from lead poisoning or even by chronic alcohol use, it presents the underlying aetiology.

MCV over 100:

Patients with vitamin B12 deficiency may report a strict vegan lifestyle without supplementation, short bowel syndrome with a history of small bowel resection, pernicious anaemia with a presentation of nausea, increased flatulence, diarrhoea, weight loss, and anorexia, malabsorptive symptoms like steatorrhea, foul-smelling stools, diarrhoea, weakness, and/or weight loss. Vitamin B12 deficiency takes many years to manifest due to hepatic storage for approximately three to six years. As a result, when this condition does present, it tends to affect the neurologic system due to its necessity in fatty acid synthesis for myelin sheaths. Patients demonstrate signs of subacute combined degeneration: cerebellar ataxia, bilateral hemiplegia, and decreased vibration and discriminative touch sensations. Folate deficiency can present with glossitis but has few other symptoms seen. However, if pregnant with a folate deficiency, the neonate can suffer from neural tube defects such as spina bifida occulta. These patients will deny the use of supplemental vitamins while pregnant. Also, chronic alcoholism can be a factor in history for a folate deficiency. Orotic aciduria presents early in life with failure to thrive and slow development reported in patients with a family history. Non-megaloblastic anaemias present as their underlying causes such as hepatic insufficiency. These patients may also report chronic alcoholism, which is the most common cause. Additionally, they can report symptoms of jaundice, fatigue, spider angiomas, palmar erythema, ascites, peripheral oedema, and even easy bleeding and bruising, to name a few symptoms. Diamond Blackfan anaemia presents in the first year of life with facial and hand malformations growth retardation and predisposition to malignancies.

MCV 80-100:

Both intrinsic and extrinsic hemolytic normocytic anaemias can present similarly. Patients have darkened urine secondary to increase urobilinogen. Intravascular hemolysis due to microangiopathic hemolytic anaemias or paroxysmal nocturnal hemoglobinuria can present with haemoglobin and hemosiderin in the urine. Many of these diseases are spontaneous, but patients with malaria can report recent travel to endemic areas, recent camping and Ixodes tick bite for babesiosis, undercooked ground beef for the hemolytic uremic syndrome, and SLE, and foamy urine indicating proteinuria with epistaxis and hypertension in a pregnant woman over 20 weeks gestation for HELLP syndrome. Aplastic anaemia can present with pallor, purpura, petechiae, increased risk of mucosal bleeding, increased risk of infection, and fatigue secondary to pancytopenia.