The blood contains many elements that, by measuring their shape and quantity levels, allow medical professionals to detect an inordinate amount of diseases and conditions. A blood test is so crucial that it’s the most frequently asked lab exam by doctors. Not only is it useful for routine check-ups and diagnosis, but also for the evaluation of a disease’s progress, such as diabetes. The 2 most common test types are a hemogram and biochemistry study, the latter of which we will cover in a different article. Keep in mind though that the ‘normal’ values contained within this article can vary from country to country, or lab to lab. A full clinical picture and analysis carried out by a physician is the best way to draw conclusions from any health test. Still, the differences in parameters among different institutions or government bodies are mostly negligible. Nevertheless, the below values are an excellent guide for drawing the line between health and pathology.
As Dr. Suzanne Salamon, assistant professor at Harvard Medical School says, explain “It’s tricky, because in some tests, a borderline result makes no difference. In others, it might indicate an important change in health that we need to follow or act on.” She further goes on to advise, “Don’t jump to conclusions. Blood test results can vary a little bit, depending on the lab. And many people are consistently on one side or the other of the normal range, and for them, that’s healthy.”1
Allows the 3 main cell types found in blood to be counted and observed in order to determine anomalies.2
- Red blood cells
- White blood cells
With a complete blood count (CBC), physicians can diagnose certain diseases, such as anemias and their subtypes3. Red blood cell count (RBC), for example, is determined by measuring the levels of hemoglobin, which transport O2 throughout all the body’s tissues. If hemoglobin is low (or too high), the physician can now begin to use other tools to assess a reason for it and move forward with a diagnosis. It also permits the evaluation of a patient’s response to some medications. Since each of the blood cell types have a crucial function, any plus or minus can be an indicator of a pathology. White blood cells fight against pathogens and infections.4 If the white blood count is very high, it’s a good sign that the body is producing or activating more of these in order to combat an existing infection or latent virus.
Platelets, on the other hand, are the ones responsible for patrolling the status and integrity of blood vessels by using the phenomena of coagulation to stop blood loss. Hence, if platelet count is very low, the person will have a difficult time stopping hemorrhages, even from minor lesions.
A hemogram also allows the lab to observe the cell’s morphology and size. Given the amount of sanguine pathologies that exist, cellular morphology studies carry a significant diagnostic value.
One analytic factor in hemograms is mean corpuscular volume, or MCV, of erythrocytes.
When MCV is greater than 100 femtoliters, it’s called macrocytosis. MCV is calculated by the formula: hematocrit % (erythrocyte volume in relation to total blood) / number of erythrocytes.5 In adults, a normal MCV value is between 80 – 99 fL6, though the exact diagnostic threshold value can slightly differ from lab to lab. Causes of enlarged red blood cells (macrocytosis) are aplastic anemia, chronic liver diseases, megaloblastic anemia, alcohol abuse, Vitamin B12 deficiency, hypothyroidism, and many more.7
On the opposite side of macrocytosis, we have microcytosis, or abnormally low MCV (below 80 femtoliters)8. Causes of microcytosis include thalassemia, iron deficiency anemia, lead poisoning, sideroblastic anemia, and chronic inflammation.
Normally, erythrocytes are biconcave, disk-shaped, flexible cells that are excellent at passing through small caliber blood vessels. However, morphological abnormalities can occur, which is denominated poikilocytosis9. Why is this bad? Simply because a misshapen erythrocyte leads to dysfunction of the same. Altered erythrocyte cells are easy to remember and observe because their name infers the type of anomalous shape. Let’s take a look at a few examples:
- Elliptocytes10: also known as ovalocytes, they’re characterized by an elongated, symmetrical, and elliptical shape of erythrocytes. Under a microscope, elliptocytes are pale at the center with hemoglobin molecules displaced at the ends. If 25% of RBC are elliptocytes, hereditary elliptocytosis is diagnosed, which is a congenital defect of the cell membrane, wherein erythrocytes lose elasticity and durability. It’s an autosomal dominant disease that originates from the mutation of genes SPTA1 (chromosome 1), EPB41 (chromosome 1), SPTB (chromosome 14), and SAO (chromosome 17).
- Dacrocytes11: so-called due to their tear-like shape, they have an elongated projection at one end, almost like a satellite. They appear as a result of serious anemias (hemolytic) and systemic diseases, such as granulomatous inflammation, myeloproliferative disease, myelofibrosis, metastatic neoplasms, leukemia, hemolytic anemia, and megaloblastic anemia, to name a few.
- Stomatocytes12: caused by a defective cell membrane, the stomatocyte is not biconcave, rather, one side of the cell is collapsed while the other side slightly bulges, bringing both ends closer and making it look like puckered lips. The presence of these indicate hereditary stomatocytosis. There are 2 types, dehydrated hereditary stomatocytosis and xerocytosis, both of which cause a permeability issue of cations through the cell membrane, resulting in the osmotic loss of H2O in the cell. The end game for these cells is earlier-than-programmed destruction, which is characteristic of hemolytic anemias such as this one. Their etiology can be congenital (genetic mutations) or acquired (low blood pH). There are several disorders that cause the appearance of stomatocytes, such as Tangier’s disease, phytosterolemia, and Rh null disease.
- Echinocytes13: identified by the presence of spicules, or sharp-like projections originating from the cell surface, which are caused by a decrease in intraerythrocytic ATP. They can also be observed in renal failure.
- Drepanocytes14: have a crescent-like shape. This morphological alteration is due to the presence of hemoglobin-S; an abnormal version of regular hemoglobin that causes erythrocytes to become stiff and deformed. They’re also called sickle-cells, and are the ones present in sickle-cell anemia.
There are other morphological alterations that can take place, such as acanthocytes15, schistocytes16, and dianocytes (Zieve’s Syndrome)17.
A standard pre-requisite for a blood test is fasting for at least some hours depending on the type of test, since food will blur the interpretation of the results. “Fasting affects the results of very few blood tests. For example, measurements of kidney, liver, and thyroid function, as well as blood counts, are not influenced by fasting. However, fasting is required before commonly ordered tests for glucose (blood sugar) and triglycerides (part of the cholesterol, or lipid, panel) for accurate results”, said William Kormos, M.D., Editor in Chief for Harvard Men’s Health Watch.18 Blood samples are taken from venous torrents by using a syringe and needle. Although, some tests require just a few drops of blood, which can be achieved with a prick of the finger.
Let’s take a look at other equally important elements (and their parameters) in the blood that a hemogram allows doctors to analyze.
For adults, normal parameters are considered to be 13.6 – 17.7 g/dl for men, and 12.1 to 15.1 g/dl for women.
Besides transporting and delivering oxygen to tissues, Hb also plays an important role in keeping the body’s acidity level at an optimum (pH 7.35 – 7.45). The mechanism in which this occurs is a simple chemical reaction. When oxygen dissociates from Hb, Hb captures available hydrogen ions from the surroundings. On the other hand, when oxygen bonds to Hb, Hb releases hydrogen ions. Since acidity is measured by the amount of free hydrogen ions in a solution (the more H+ ions, the more acidic), we can see how the ability of hemoglobin to capture and release oxygen plays a central role in pH regulation. 20
Low levels of Hb can be caused by renal failure, hypothyroidism anemia, cirrhosis, porphyria, leukemia, lymphoma, medications, and hemorrhages. 21
In turn, a high reading of Hb can be caused by pulmonary fibrosis, tobacco smoke, emphysema, dehydration, renal tumors, polycythemia vera, and congenital heart disease22; as can the use of hormones, such as erythropoietin.
Refers to the volume of red blood cells in relation to total blood volume and is expressed as a percentage. In men, normal is 40% – 54%23, whereas women are in the 36% – 48% range. The difference in parameter values between the sexes is due to the fact that, on average, men have approximately 33% more muscle mass than women. As such, oxygen requirements are higher in men.
Calculating Hct is usually done automatically by lab machines, which multiplies the values of mean cell volume (see below) and RBC, following by dividing that value by 10:
HCT (%) = (MCV x RBC) / 10
Naturally, if MCV and RBC values are not accurate, an erroneous Hct reading will be the result.24
Hct can also show the amount of hemoglobin present in RBC, since a low Hct count can be an expression of low hemoglobin and RBC, as is the case with some anemias. Causes of low Hct25 are multiple myeloma, lymphoma, and leukemia among others. If Hct is higher than normal, aplastic anemia, colon cancer, internal bleeding, thalassemia, and myelodysplastic syndrome.
A high Hct reading indicates a decreased amount of fluid, or plasma in the blood, which is commonly due to dehydration. In this case, simply drinking the recommended amounts of liquids should correct Hct levels, making it a transitory issue. 26
However, persistently high levels of Hct, erythropoietin, and Hb can be a red flag for polycythemia Vera; a condition in which the bone marrow hyper-produces red blood cells. Other causes of elevated Hct are congenital heart disease, genetic alterations, lung disease, cigarette smoke, and excess erythropoietin.27
Mean Corpuscular Hemoglobin (MCH)
Measures the average amount of hemoglobin in any given erythrocyte28. Normal parameters are between 27 – 31 picograms/cell. The values of MCH allows doctors to differentiate between hyperchromic (high MCH reading) and hypochromic (low MCH reading).
Macrocytosis is associated with hyperchromic anemia, while microcytosis is usually correlated to hypochromic anemia.
A low level MCH reading can be caused by iron deficiency anemia, constant hemorrhaging (as a consequence of hemorrhoids), inflammatory bowel disease, and hematuria. 29
MCH is calculated by using the formula: (Hb x 10) / RBC = MCH.
Mean Corpuscular Volume (MCV)
This indicator shows the average size of red blood cells30. It’s calculated by the formula
Hct / RBC and is expressed in fL/cell. In adults. See page 1 for more details.
Platelets – AKA Thrombocytes
Produced in the bone marrow as a result of defragmentation of megakaryocytes, platelets are the most important agents in coagulation and blood vessel repair31. Any abnormal count or morphology can result in severe dysfunction; and as a consequence, many diseases. Normal platelet count is 150,000 – 400,000 per µl (microliter) of blood32.
Von-Willebrand disease is the most predominant of all platelet dysfunction disorders33, and is characterized by the inability of the thrombocytes to adhere to vascular walls due to a lack or dysfunction of the all-important von-Willebrand factor found in plasma. Thus, proper clotting in the event of hemorrhage is delayed or non-existent. Other less common platelet-associated disorders are Wiskott-Aldrich syndrome (low platelet count), Bernard-Soulier syndrome (adhesion disorder), Glanzmann thrombasthenia (platelet aggregation disorder), Chediak-Higashi syndrome, and Gray platelet syndrome (platelet secretion disorder).34
A high count of platelets is called thrombocytosis35, which can be primary (also called essential) or secondary (as a result of another condition, or infection) in origin. The former is caused by an overproduction on the part of the bone marrow as a consequence of mutagenic phenomena in the genes JAK2, MPL, THPO, TET2 and CALR. The first 4 give instructions for building proteins that induce cells to proliferate. Whereas the protein encoded by CALR, called calreticulin, helps maintain mineral homeostasis by binding to calcium ions and regulating their storage in cell organelles, such as the ER. 36. The first 4 give instructions for building proteins that induce cells to proliferate.
Secondary thrombocytosis can appear due to leukemia, polycythemia Vera, iron-deficiency anemia, lymphoma, rheumatoid arthritis, and after a splenectomy.
A low platelet count is called thrombocytopenia, and is associated with acute infection, systemic lupus erythematosus, hemolytic uremic syndrome, pernicious anemia, the use of some medications (heparin, anti-inflammatories, anti-hypertensives, and anti-convulsive drugs); Vitamin B12 deficiency, and chemotherapy. Symptoms include bleeding gums, blood in urine or stool, nosebleeds, and heavier-than-usual menstruations. These symptoms can appear in any degree of thrombocytopenia, but they’re more common when platelet count drops to 50,000 µl and lower.37
One of the most important leukocytes (white blood cells) of the immune system, lymphocytes become activated during microbial infections to aid the body in defense38. They comprise around 20% – 40% of the total white blood cells (WBC). In a hemogram, normal parameters are 1,000 – 4,800 per µl of blood in adults, and 3,000 – 9,500 per µl in children39. When an antigen is present in the circulatory system and lymphatic tissue, several immunological mediators help to activate the lymphocytes and guide them to the required site of action. They’re excellent trackers of antigens, and are capable of using mechanisms that allow them to detect repeated invasion by the same antigen.
While lymphocytes are the smallest of all WBC, they’re role is crucial in defense, where they strenuously fight off invasion every day. There are 3 types40:
- NK (natural killers): in charge of destroying infected cells.
- T-cells: involved in detecting peptide antigens from different pathogens and destroying cells that contain antigenic material. They originate in the thymus gland.
- B-cells: produced in the bone marrow; in charge of creating and releasing antibodies.
A high lymphocyte count can be caused by infectious mononucleosis, acute parotitis, lymphocytic leukemia, viral hepatitis, non-Hodgkin’s lymphoma, and tuberculosis.41
Low lymphocyte levels, known as lymphopenia, can be associated with HIV, influenza virus, hepatitis, chemotherapy, Hodgkin’s lymphoma, physical trauma, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, Kaposi sarcoma, and lymphoproliferative disorders.
Also part of the WBC family, neutrophils comprise 40%-75% of the total WBC count in healthy individuals, making them the most abundant leukocyte.42 Their function is to regulate inflammatory responses, interact with different immune mediators and cells, and to search & destroy invading pathogens via phagocytosis and intracellular degradation43.
An elevated neutrophil count is called neutrophilia44, and can be associated with emotional stress, strenuous physical exercise, bacterial and viral infections, septicemia, acute osteomyelitis, diabetes, uremia, cancer, hepatic necrosis, hemolytic anemia, and chronic myeloid leukemia.
An interesting feature of neutrophils is that they are present in 2 ways relative to their nucleus morphology that gives medical professionals a clue about their usage and age: segmented (mature) and bands (immature). The latter describes newly produced neutrophils designed for battle against the trespassing antigen, and the former describe what the nucleus of older neutrophils look like, which can be used to tell how long the body has been fighting the infection for.
A low neutrophil count is known as neutropenia45. It can occur as a consequence of cirrhosis, hypothyroidism, typhoid fever, malaria, Kostmann syndrome, myelodysplastic syndromes, and infection.
They measure about 12-17 µm in diameter and exclusively originate in the bone marrow. Eosinophil maturation takes about 8 days, when it is then released into the bloodstream after differentiation. However, their lifespan is about 10 hours on average. Despite their short-lived presence, they provide various essential immunological roles46, such as phagocytosis, endocytosis, effector of immediate hypersensitivity, chemotaxis, chemokinesis, cytotoxicity, and destruction of parasites and bacteria. Unlike their WBC kin, eosinophils are very versatile in functionality, so much so that it’s hard to pinpoint one primary role, since their multifunctional attributes intersect with so many immunological processes. However, research suggests that they are mainly involved in many inflammatory allergic responses. In a hemogram, normal parameter values range between 0% and 3%, or 50 – 500 per mL.47
When there is an elevated number of eosinophils circulating in the blood, it’s called eosinophilia48. The cause can be primary (when the culprit is a genetic dysfunction that leads to hyper-proliferative processes) or secondary (as a result of an underlying cause, for example, parasitic infection). The most common are allergic conditions, such as asthma and rhinitis. However, it can also be observed with infection, helminth invasion, and Hodgkin’s lymphoma.
On the contrary, eosinopenia (low levels of eosinophils)49 can be a consequence of Cushing’s disease, exogenous glucocorticoids, decreased bone marrow production, aplastic anemia, HIV, and severe infection (skin, urinary, genital).
With the above information, a hemogram test result will make much more sense, in terms of what all the indicators mean and what they represent. There are still other factors to consider in a hemogram, such as the biochemical composition of blood as mentioned in the beginning of this article, where elements like sodium, potassium, calcium, iron, and phosphorus, all have a role to play and an interaction to be had with RBC, WBC, platelets, and other cells of different tissues, but we’ll overstep the boundaries of the topic at hand, which is the overview of cellular factors of interest in a hemogram. Of course, the above information should not substitute information provided by your physician, nor should it be misconstrued as a tool for diagnosis. Rather, it is a guide to help patients better understand what can seem to be intimidating information on their hemogram results. With a well-rounded review of what cellular over-proliferation and dysfunction means, patients can better understand why doctors encourage a healthy approach to diet and lifestyle choices.
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