Complete blood count is by far the most ordered blood investigations by physicians and for good reason. The test is cheap, easy to perform and minimally invasive. It can also exclude or confirm a wide range of diagnoses and can be a useful screening tool for many other common disorders which can be used as a starting point to do other more invasive tests for those who need them. Understanding some values in a blood test should be common knowledge since they should be done on a routine basis and understanding the meaning of some results is considered a common knowledge in some societies.
Red blood corpuscles
Our blood is the perfect transportation medium. It is fluid, moves in elastic pipes we call vessels and can coagulate when needed to plug holes in this pipe system as they form. The most important function of blood is the transportation of oxygen which is essential for all energy production in our cells. This function is so essential that some tissues in our body can die if deprived of oxygen for as little as 4 minutes (nerve cells). This function is possible thanks to red blood cells. The term “red blood cells” is actually a misnomer since they are not technically “cells” for they lack nuclei, so they are termed corpuscles, but the name “cells” persists for historical context.
Red blood corpuscles are the most predominant in our blood followed by white blood cells then platelets. They transport oxygen inspired by the lungs through a network of capillaries surrounding the lung alveoli (air sacs). Oxygen is carried on a protein called hemoglobin within red cells. Hemoglobin is formed of 2 portions, the heme which is an iron containing compound and the globin which is a protein. Each hemoglobin molecule can bind four oxygen molecules.
Hemoglobin
Hemoglobin level in blood is one of the most important parameters in a CBC. Normal hemoglobin level is 13.8-17.2 grams per deciliter in adult males and 12.1-15.1 in adult females. The difference is related to the level of testosterone in males which is a stimulant for increased production of red cells as well as the chronic loss of blood in fertile females in the form of menses.
If hemoglobin level falls below 13.8 in males or 12.5 in females, it is called anemia, and anemia is not a clinical term but a laboratory one since not all anemias are symptomatic and not all normal hemoglobin levels are asymptomatic. If hemoglobin level is more than 17.2 in males or 15.1 in females, it is termed polycythemia, and polycythemia can result from natural causes such as living at high altitudes or from diseases such as chronic obstructive pulmonary disease, chronic testosterone use in athletes or from some cancers like chronic myeloid leukemia or polycythemia vera.
Dangerously low hemoglobin levels
There is much debate regarding which hemoglobin level that should be considered dangerously low among doctors and there is no clear cutoff point. The common definition is that it is the level at which a doctor will transfuse red blood cells to avoid complications and it is placed between 7 grams per deciliter in a previously healthy adult with no heart problems to 8.8 grams in a critically ill patient with a previous heart condition especially heart attacks.
At such low levels of hemoglobin, symptoms tend to be severe including severe fatigue and weakness, awareness of a racing heartbeat, fainting and severe dizziness. At such levels, the body can’t get enough oxygen and tries to compensate by increasing the heart rate to better deliver oxygen to tissues which causes the patient to feel that their heart is racing. This can be enough until a certain level when the heart contracts so quickly that it barely relaxes to fill with blood -heart filling occurs during the relaxation phase-. This will eventually cause heart failure which is the cause of death in anemia. Other symptoms can also include chest pain similar to that seen in heart attacks because there is a mismatch between the work the heart does and the oxygen delivered to its muscle. This pain is commonly felt like a tightening sensation underneath the breastbone which is exacerbated by work and exercise and relieved partially or totally at rest.
Are high hemoglobin levels dangerous?
Unlike anemias, polycythemia doesn’t receive much public attention first because it is not a “deficiency” and secondly because it is far less common than anemias. It is, however, not a mild condition and complications can occur either because of the condition that caused polycythemia in the first place like smoking, chronic obstructive pulmonary disease or steroid use or as a result of polycythemia itself. Complications of polycythemia include:
- High risk of blood clotting: Polycythemia increases the density of red cells and favors the occurrence of blood clot. Blood becomes more viscid leading to a more sluggish circulation which causes platelets to aggregate and form a blood clot. This can also occur in some conditions like polycythemia vera where platelets increase in number along with red cells. Blood clots can occur in the deep veins of the leg especially on long sitting like in flights, and then they may dislodge and cause pulmonary embolism (blood clots in the lung) which can be fatal. Blood clots can also occur in the coronary arteries causing heart attacks, or in the cerebral blood vessels causing strokes.
- Symptoms of vascular insufficiency: Even without clotting, the sluggish viscid blood can hardly transport oxygen to tissues causing a multisystem affection which can appear in the form of anginal chest pain, cramping pain in the calves and decreased exercise tolerance. Other symptoms of this condition include ear tinnitus (continuous machine-like humming or ringing sound in the ears), headache and dizziness.
- High blood pressure: The fluidity of blood is a major contributing factor to blood pressure and if the blood’s viscosity increases, blood pressure will surely rise.
Hematocrit
The second important value in a CBC is the hematocrit. Hematocrit is the ratio of the volume of red cells in relation to the whole volume of blood. It is a simple test but can detect anemia just like hemoglobin level. It is measured by collecting a sample of venous blood, placing it in a thin cylinder and centrifuging it which allows for cells to settle at the bottom of the tube. Red cells will be separated from the yellowish plasma and their volume can be measured.
Normal values of hematocrit are 41-50% in males and 36-48% in females and the sex discrepancy of this value is attributed to the same causes as those of hemoglobin level. Generally, hematocrit doesn’t provide much more data than hemoglobin level, but it can also be used to detect severe dehydration where its level will rise. High hematocrit also occurs in polycythemia. Hematocrit has another more important significance which is determining the mean corpuscular volume (MCV) of red blood corpuscles which will be explained later in this article.
Red cell count
The third value usually listed in a complete blood count is the red cell count. Red cell count isn’t usually correlated with anemia and many anemias can have normal cell count. It, however, correlates with the bone marrow’s ability to produce cells and is greatly decreased in cases of aplastic anemia. Red cell count was traditionally determined through examining a sample of the patient’s blood under the microscope and manually counting red cells then multiplying the number by the volume of blood. This method is now obsolete and is replaced by the automated analyzer which determines red cell count using laser optical light dispersion which is far more accurate and time-saving.
Red cell count is also useful for determining the parameters of each cell by using its value as a denominator for example:
- Mean corpuscular hemoglobin: This value refers to the amount of hemoglobin found in a single red corpuscle. It is measured by dividing hemoglobin level to the number of red cells in a given volume of collected blood. Its measuring unit is picogram which is one millionth of a gram. Normal values range between 27-31 picograms, and cells which have a low hemoglobin content are said to be
- Mean corpuscular volume: Mean corpuscular volume is the volume of a single red corpuscle. It is calculated by dividing hematocrit -which is the volume of all red cells in a certain volume of blood- to the number of cells in the same volume. Its measuring unit is femtoliter which is one millionth billionth of a liter (that’s 15 zeros). Normal values range from 81-89 fl. If a cell has a large MCV, it is said to be macrocytic, and if it has a small MCV, it is said to be
Reticulocyte count
Red cells pass by different stages before being released into the circulation, the last of which is called reticulocytes. Reticulocytes mature in 24-48 hours in the bone marrow and are then released as mature red cells. This controls the level of reticulocytes at 0.5-2% of all red corpuscles. They are detected using automated cell counters with the help of special fluorescent dyes and laser techniques to differentiate them from mature red cells. They are also stained with a special methylene blue stain to be visualized under the microscope. What is peculiar, however, is that red cells become smaller when they mature which means that if the reticulocyte count is high, larger cells will be found in the circulation and the MCV tends to be high.
Causes of elevated reticulocyte count include conditions which cause the destruction or loss of red cells at a rate higher than what the bone marrow can replace. It is usually seen in hemolytic anemias -anemias where red cells are destroyed by the effect of antibodies or toxic materials in the blood stream-, in cases of chronic yet slow loss of blood and following an attack of acute loss of blood. Reticulocyte count is, however, a marker of a healthy active bone marrow which responds to anemia. If reticulocyte count fails to rise in response to anemia it can indicate one or more of the following:
- Bone marrow failure following chemotherapy or cancer.
- Uncorrected iron deficiency anemia.
- Vitamin B12 or folate deficiency.
- Decreased levels of erythropoietin, a hormone secreted by the kidney which is decreased in cases of renal failure. It plays a vital role in stimulating the bone marrow to produce red blood corpuscles.
Classifying anemias
Anemias are classified according to the size and hemoglobin content of individual red corpuscles into three broad categories:
- Microcytic hypochromic anemia: This means that red cells are smaller than 80 fl in MCV and have a lower hemoglobin concentration than 27 pg. This type of anemia is usually seen in iron deficiency, anemia of chronic illness -the minority of cases- and in lead poisoning. It can also occur due to very slow chronic loss of blood which depletes the body of its iron stores. The other major condition that is characterized by microcytic hypochromic anemia is thalassemia major. It is a hereditary blood disorder due to abnormal hemoglobin protein and is also characterized by abnormal facial features as well as stunted growth and sexual maturity.
- Normocytic normochromic anemia: In this type of anemia, red cells have a normal volume and hemoglobin content, rather the cause of anemia is their decreased numbers. This is usually seen in:
- Acute hemorrhage: Acute hemorrhage whether internal or external causes a drop of red cell count before the bone marrow tries to compensate, which takes days.
- Acute hemolytic anemia: Acute destruction of red cells by autoimmune processes or as a reaction to food or drugs will cause a rapid drop of blood count before the bone marrow replaces them.
- Renal failure: Anemia resulting from renal failure is usually normocytic normochromic due to the drop in the level of erythropoietin which is secreted in the juxtaglomerular apparatus of the kidney.
- Hypothyroidism: Hypothyroidism can, in fact, cause all three types of anemia and normocytic anemia is a common first presentation of the condition. It occurs because thyroid hormone is an important stimulus for erythropoietin production.
- Bone marrow failure and aplastic anemia: When bone marrow fails whether due to cancer, chemotherapy or other drugs, it usually presents with a normocytic normochromic anemia.
- Macrocytic anemia: Macrocytic anemia is when the red cell size is more than 90 fl. It usually means that such cells are immature and were either released prematurely or couldn’t complete their maturation because of a deficiency of a certain nutrient. It is seen in the following cases:
- Vitamin B12 deficiency: This type of anemia is called pernicious anemia and results from dietary deficiency of vitamin B12. Vitamin B12 is necessary for the production of DNA and its deficiency can affect cellular maturation. This vitamin is very poor in plant sources and is usually found in meat, poultry, eggs and dairy products. It can also occur in some conditions of the stomach if a certain protein called intrinsic factor is not produced since it is necessary for the absorption of vitamin B12.
- Folic acid deficiency: Folic acid is essential for DNA formation and its deficiency causes lack of maturation of cells and the development of macrocytic anemia. Folic acid deficiency is usually dietary.
- Reticulocytosis: As mentioned above, any cause of increased reticulocyte count will cause increased MCV and macrocytic anemia.
- Liver diseases: Liver disease can cause increased cholesterol deposition on red cells causing their volume to increase. The liver can also cause anemia due to depleted stores of iron, concomitant affection of the kidney, chronic bleeding because of portal hypertension and impaired coagulation, and vitamin deficiencies.
- Alcohol abuse: Alcohol has a direct toxic effect on the bone marrow and also decreases the absorption of vitamin B12.
Red cell distribution width (RDW)
Red cell distribution width is an essential component of any complete blood count. It represents the range of variation of red cell volume and size. It is a value obtained after the automated analyzer makes a graphical representation of all red cell sizes. Normal range lies between 11.5 and 15.4%. When it rises above 15.4, RDW is increased in the following conditions:
- Iron deficiency anemia: High RDW is a cardinal feature in iron deficiency anemia and is seen in virtually all cases. It can help differentiate iron deficiency anemia from other causes of microcytic hypochromic anemia.
- Vitamin B12 and folate deficiency: Due to the large red cells in macrocytic anemia, the variation between cellular sizes in this condition is seen in many cases.
- Spherocytosis: Spherocytosis is a hereditary blood disorder where the red cells are spherical in shape instead of biconcave which can cause a variation in their size. High RDW is, however, not found in many cases.
Treating anemia
A common misconception is that anemia is a singular disease that is manageable by a single medication or regimen, yet it is a heterogenous condition with many causes. The main treatment of anemia is to identify what caused it in the first place then to correct it. The only immediate correction of anemia is blood transfusion which is never considered unless the condition is life-threatening since blood transfusion is associated with its own set of complications including immunological reactions and infections.
An example to demonstrate why we don’t take anemia lightly is that when anemia results from iron deficiency, we have to be sure that that deficiency is dietary before prescribing iron supplements since it can point towards a chronic loss of blood which is far more serious than a dietary deficiency. Similarly, normochromic normocytic anemia can be caused by acute loss of blood, autoimmune diseases like systemic lupus or as a reaction to drugs or food with hemolysis which can occur in case of favism after ingesting fava beans or sulfa-containing drugs. Autoimmune anemia can be associated with other life-threatening disease like systemic lupus which has to be managed more urgently especially if the anemia is not severe.
Bone marrow disorders should also be considered in case of anemia especially if the patient is old or if it is associated with deficiency of other blood elements like white cells and platelets. Patients presenting with multiple cellular deficiencies often complain of easy bruising and spontaneous bleeding with the anemia as well as recurrent infections due to the low white cell count. Aplastic anemia is the term given to anemia due to decreased production by the bone marrow. It can be treated by managing the original cause or by bone marrow transplantation according to the cause of the condition and its severity. Anemia due to renal failure is treated by supplying the body with the deficient erythropoietin and anemia of endocrinological causes like hypothyroidism needs management of the original condition.
Overall, treating anemia should be only done at the hands of your doctor. Simple dietary anemias are treated by a GP, but if the doctor suspects a more serious condition or a condition that requires additional investigations, then they will refer you to a hematologist to ensure an accurate diagnosis and a thorough management. What you can do, however, is to protect yourself against it by following a balanced diet of proteins, carbohydrates and fats. Ensure that your refined sugars intake is kept to a minimum and to visit your doctor if you feel any of the symptoms of anemia.