A complete blood count (CBC), is a set of medical laboratory tests that provide information about the cells in a person’s blood.
It indicates the counts of white blood cells, red blood cells and platelets, the concentration of hemoglobin, and the hematocrit (the volume percentage of red blood cells).
The red blood cell indices, which indicate the average size and hemoglobin content of red blood cells, are also reported, and a white blood cell differential, which counts the different types of white blood cells, may be included.
The CBC can be used to monitor health or diagnose diseases by comparing it to reference ranges, which vary with sex and age.
Conditions like anemia and thrombocytopenia are defined by abnormal complete blood count results.
The red blood cell indices provide information about the cause of a person’s anemia : iron deficiency and vitamin B12 deficiency.
The results of the white blood cell differential can help to diagnose viral, bacterial and parasitic infections and blood disorders like leukemia.
Not all results falling outside of the reference range require medical intervention.
The CBC performed by an automated hematology analyzer counts cells and imparts information on their size and structure.
The concentration of hemoglobin is measured, red blood cell indices are calculated from measurements of red blood cells and hemoglobin.
Similarly, manual testing can be used to independently confirm abnormal results.
Approximately 10–25% of samples require a manual blood smear review, in which the blood is stained and viewed under a microscope to verify that the results are consistent with the appearance of the cells and to look for abnormalities.
The hematocrit can be determined manually by centrifuging the sample and measuring the proportion of red blood
In the absence of automated instruments, blood cells are counted under the microscope using a hemocytometer.
The Coulter principle uses electrical impedance measurements to count blood cells and determine their sizes.
The use of optical measurements to count and identify cells, has enabled the automation of the white blood cell differential.
The red blood cells, carrying oxygen are predominant and give rise to the color of blood.
The white blood cells are part of the immune system.
The platelets are needed to form clots, which prevent excessive bleeding.
Blood is composed of the fluid portion, plasma, and a cellular portion that contains red blood cells, white blood cells and platelets.
The complete blood count evaluates the three cellular components of blood.
The CBC results are useful for investigating a wide range of conditions, and is used to screen for diseases as part of a medical assessment.
The results may indicate a need for a blood or platelet transfusion.
CBCs are performed before a person undergoes surgery to detect anemia, ensure that platelet levels are sufficient, and screen for infection, as well as after surgery, so that blood loss can be monitored.
In emergency medicine, the CBC is used to investigate numerous symptoms, such as fever, abdominal pain, and shortness of breath, and to assess bleeding and trauma.
Blood counts are monitored in people undergoing chemotherapy or radiation therapy for cancer, because these treatments suppress the production of blood cells.
Regular CBCs are necessary for people taking some psychiatric drugs, such as clozapine and carbamazepine, which in rare cases can cause a drop in the number of white blood cells (agranulocytosis).
The complete blood count is a routine part of prenatal care; and in newborn babies.
A CBC may be needed to investigate jaundice or to count the number of immature cells in the white blood cell differential, which can be an indicator of multiple disease processes.
The CBC and smear examination reflect the functioning of the hematopoietic system.
Pancytopenia) can indicate that blood cell production is being affected by a marrow disorder, abnormal cells on the blood smear might indicate acute leukemia or lymphoma, while an abnormally high count of neutrophils or lymphocytes, in combination with indicative symptoms and blood smear findings, may raise suspicion of a myeloproliferative disorder or lymphoproliferative disorder.
Examination of the CBC results and blood smear can help to distinguish between causes of anemia, such as nutritional deficiencies, bone marrow disorders, acquired hemolytic anemias and inherited conditions like sickle cell anemia and thalassemia.
Reference ranges for the complete blood count represent the range of results found in 95% of apparently healthy individuals.
Most analyzers directly measure the average size of red blood cells, which is called the mean cell volume (MCV), and calculate the hematocrit by multiplying the red blood cell count by the MCV.
The hemoglobin concentration, the red blood cell count and the hematocrit are used to calculate the average amount of hemoglobin within each red blood cell, the mean corpuscular hemoglobin (MCH); and its concentration, the mean corpuscular hemoglobin concentration (MCHC).
The red blood cell distribution width (RDW), is derived from the standard deviation of the mean cell volume and reflects variation in cellular size.
White blood cells form three distinct peaks which correspond roughly to populations of granulocytes, lymphocytes, and other mononuclear cells, allowing a three-part differential to be performed based on cell volume alone.
More advanced analyze provide a five- to seven-part differential, such as light scattering or radiofrequency analysis, using dyes to stain specific chemicals inside cells—for example, nucleic acids, which are found in higher concentrations in immature cells or myeloperoxidase, an enzyme found in cells of the myeloid lineage.
Basophils may be counted in a separate channel where a reagent destroys other white cells and leaves basophils intact.
An approach to automating the differential count is the use of digital microscopy software, which uses artificial intelligence to classify white blood cells from photomicrographs of the blood smear.
The cell images are displayed to a human operator, who can manually re-classify the cells if necessary.
Most analyzers take less than a minute to run all the tests in the complete blood count.
The results are very precise, but some abnormal cells may not be identified correctly, requiring manual review.
Automated results are flagged for manual blood smear review in 10–25% of cases.
To investigate these issues, blood is spread on a microscope slide, stained with a Romanowsky stain, and examined under a microscope.
Changes in the appearance of red blood cells can have diagnostic significance: sickle cells is indicative of sickle cell disease, and a high number of fragmented red blood cells (schistocytes) requires investigation as it can suggest a microangiopathic hemolytic anemia.
In some inflammatory conditions and in paraprotein disorders like multiple myeloma, high levels of protein in the blood may cause rouleaux.
Some parasitic diseases, such as malaria and babesiosis, can be detected by finding the causative organisms on the blood smear.
The platelet count can be estimated from the blood smear.
To perform a manual white blood cell differential, the microscopist counts 100 cells on the blood smear and classifies them based on their appearance.
This gives the percentage of each type of white blood cell, and by multiplying these percentages by the total number of white blood cells, the absolute number of each type of white cell can be obtained.
Manual counting is subject to sampling error because so few cells are counted compared with automated analysis.
Manual review can identify abnormal cells that analyzers cannot, such as the blast cells seen in acute leukemia.
Clinical features like toxic granulation and vacuolation can also be ascertained from microscopic examination of white blood cells.
The hematocrit can performed manually by filling a capillary tube with blood, centrifuging it, and measuring the percentage of the blood that consists of red blood cells.
Some conditions that can cause automated hematocrit results to be incorrect, such as polycythemia or severe leukocytosis which vacancy interferes with red blood cell measurements by causing white blood cells to be counted as red cells.
Red blood cells deliver oxygen from the lungs to the tissues and on their return carry carbon dioxide back to the lungs where it is exhaled.
Assuming that the red blood cells are normal, there is a constant relationship between hemoglobin and hematocrit: the hematocrit percentage is approximately three times greater than the hemoglobin value in g/dL, plus or minus three.
This relationship, is known as the rule of three, can be used to confirm that CBC results are correct.
The MCH is a measure of the average amount of hemoglobin per red blood cell.
The MCHC gives the average proportion of the cell that is hemoglobin.
The MCH does not take into account the size of the red blood cells whereas the MCHC does.
Collectively, the MCV, MCH, and MCHC are referred to as the red blood cell indices.
Changes in these indices are visible on the blood smear: red blood cells that are abnormally large or small can be identified by comparison to the sizes of white blood cells, and cells with a low hemoglobin concentration appear pale.
Another parameter is calculated from the initial measurements of red blood cells: the red blood cell distribution width or RDW, which reflects the degree of variation in the cells’ size.
An abnormally low hemoglobin, hematocrit, or red blood cell count indicates anemia.
\Anemia points to an underlying condition affecting the person’s red blood cells.
General causes of anemia include blood loss, production of defective red blood cells, ineffective erythropoeisis, decreased production of red blood cells and increased destruction of red blood cells.
An increased number of red blood cells, leading to an increase in the hemoglobin and hematocrit, is called polycythemia.
Dehydration or use of diuretics can cause a relative polycythemia by decreasing the amount of plasma compared to red cells.
A true increase in the number of red blood cells, absolute polycythemia, can occur when the body produces more red blood cells to compensate for chronically low oxygen levels in conditions like lung or heart disease, or when a person has abnormally high levels of erythropoietin, a hormone that stimulates production of red blood cells.
Polycythemia vera, the bone marrow produces red cells and other blood cells at an excessively high rate.
Evaluation of red blood cell indices help determine the cause of anemia.
If the MCV is low, the anemia is termed microcytic, while anemia with a high MCV is called macrocytic anemia.
Anemia with a low MCHC is called hypochromic anemia.
If anemia is present but the red blood cell indices are normal, the anemia is considered normochromic and normocytic.
Elevation of the MCHC above the upper reference value is rare, mainly occurring in conditions such as spherocytosis, sickle cell disease and hemoglobin C disease.
An elevated MCHC can also be a false result from conditions like red blood cell agglutination (which causes a false decrease in the red blood cell count, elevating the MCHC) or highly elevated amounts of lipids in the blood (which causes a false increase in the hemoglobin result).
Microcytic anemia is typically associated with iron deficiency, thalassemia, and anemia of chronic disease, while macrocytic anemia is associated with alcoholism, folate and B12 deficiency, use of some drugs, and some bone marrow diseases.
Acute blood loss, hemolytic anemia, bone marrow disorders, and various chronic diseases can result in anemia with a normocytic blood picture.
The MCV is relatively stable over time compared to other CBC parameters, so a large change in MCV may indicate that the sample was drawn from the wrong patient.
A low RDW has no clinical significance, but an elevated RDW represents increased variation in red blood cell size, a condition known as anisocytosis.
The RDW is highly elevated at birth and gradually decreases until approximately six months of age.
Anisocytosis is common in nutritional anemias such as iron deficiency anemia and anemia due to vitamin B12 or folate deficiency, while people with thalassemia may have a normal RDW.
The CBC results suggests further investigation for anemia, such as a ferritin test to confirm the presence of iron deficiency, or hemoglobin electrophoresis to diagnose a hemoglobinopathy such as thalassemia or sickle cell disease.
A high white blood cell count, which is called leukocytosis, often occurs in infections, inflammation, and states of physiologic stress.
It can also be caused by diseases that involve abnormal production of blood cells, such as myeloproliferative and lymphoproliferative disorders.
A decreased white blood cell count, termed leukopenia, can lead to an increased risk of acquiring infections, and occurs in treatments like chemotherapy and radiation therapy and many conditions that inhibit the production of blood cells.
Sepsis is associated with both leukocytosis and leukopenia.
The total white blood cell count is usually reported in cells per microlitre of blood (/μL) or 109 cells per litre (× 109/L).
In the white blood cell differential, the different types of white blood cells are identified and counted.
The results are reported as a percentage and as an absolute number per unit volume.
Five types of white blood cells—neutrophils, lymphocytes, monocytes, eosinophils, and basophils—are typically measured.
Precursors of neutrophils; specifically, promyelocytes, myelocytes and metamyelocytes may be seen and reported.
Differential results are useful in diagnosing and monitoring many medical conditions.
An elevated neutrophil count (neutrophilia) is associated with bacterial infection, inflammation, and myeloproliferative disorders, while a decreased count (neutropenia) may occur in individuals who are undergoing chemotherapy or taking certain drugs, or who have diseases affecting the bone marrow.
Neutropenia can also be caused by some congenital disorders and may occur transiently after viral or bacterial infections in children.
People with severe neutropenia and clinical signs of infection are treated with antibiotics to prevent potentially life-threatening disease.
An increased number of band neutrophils—young neutrophils that lack segmented nuclei—or immature granulocytes is termed left shift and occurs in sepsis and some blood disorders, but is normal in pregnancy.
An elevated lymphocyte count (lymphocytosis) is associated with viral infection and lymphoproliferative disorders like chronic lymphocytic leukemia.
Elevated monocyte counts (monocytosis) are associated with chronic inflammatory states;
The eosinophil count is often increased (eosinophilia) in parasitic infections and allergic conditions.
An increased number of basophils, termed basophilia, can occur in myeloproliferative disorders like chronic myeloid leukemia and polycythemia vera.
The presence of some types of abnormal cells, such as blast cells or lymphocytes with neoplastic features, is suggestive of a hematologic malignancy.
Platelets play an essential role in clotting.
When the wall of a blood vessel is damaged, platelets adhere to the exposed endothelial surface at the site of injury and plug the gap.
Simultaneously there is activation of the coagulation cascade resulting in the formation of fibrin, which reinforces the platelet plug to create a stable clot.
A low platelet count, (thrombocytopenia), may cause bleeding if severe.
Thrombocytopenia can occur in patients undergoing treatments that suppress the bone marrow, such as chemotherapy or radiation therapy, or taking certain drugs, such as heparin, that can induce the immune system to destroy platelets.
Thrombocytopenia is a feature of many blood disorders, like acute leukemia and aplastic anemia, as well as some autoimmune diseases.
Thrombocytosis, a high platelet count, may occur in states of inflammation or trauma, as well as in iron deficiency
Platelet count may reach exceptionally high levels in people with essential thrombocythemia.
The platelet count can be reported in units of cells per microlitre of blood (/μL), 103 cells per microlitre (× 103/μL), or 109 cells per litre (× 109/L).
The mean platelet volume (MPV) measures the average size of platelets in femtolitres.
The mean platelet volume (MPV) aid in determining the cause of thrombocytopenia.
An elevated MPV may occur when young platelets are released into the bloodstream to compensate for increased destruction of platelets, while decreased production of platelets due to dysfunction of the bone marrow can result in a low MPV.
The MPV is also useful for differentiating between congenital diseases that cause thrombocytopenia.
Reticulocyte count
Red blood cells stained with new methylene blue: the cells containing dark blue structures are reticulocytes.
Reticulocytes are immature red blood cells, which, unlike the mature cells, contain RNA.
A reticulocyte count is sometimes is, usually to investigate the cause of an anemia or evaluate the response to treatment.
Anemia with a high reticulocyte count can indicate that the bone marrow is producing red blood cells at a higher rate to compensate for blood loss or hemolysis.
Anemia with a low reticulocyte count may suggest that the person has a condition that reduces the body’s ability to produce red blood cells.
With nutritional anemia, nutrient supplementation results in an increase in the reticulocyte count indicating a response to the treatment by producing more red blood cells.
Hematology analyzers perform reticulocyte counts by staining red blood cells with a dye that binds to RNA and measuring the number of reticulocytes through light scattering or fluorescence analysis.
The reticulocyte countbtest can be performed manually by staining the blood with new methylene blue and counting the percentage of red blood cells containing RNA under the microscope.
The reticulocyte count is expressed as an absolute number or as a percentage of red blood cells.
Some instruments measure the average amount of hemoglobin in each reticulocyte; an indicator of iron deficiency in people who have conditions that interfere with standard tests.
The immature reticulocyte fraction (IRF) is a measurement produced by some analyzers which quantifies the maturity of reticulocytes: cells that are less mature contain more RNA and thus produce a stronger fluorescent signal.
Such information can be useful in diagnosing anemias and evaluating red blood cell production following anemia treatment or bone marrow transplantation.
During their formation in bone marrow, and in the liver and spleen in fetuses, red blood cells contain a cell nucleus, which is usually absent in the mature cells that circulate in the bloodstream.
Nucleated red blood cells are normal in newborn babies, but when detected in children and adults, they indicate an increased demand for red blood cells, which can be caused by bleeding, some cancers and anemia.
High numbers of nucleated red cells can cause a falsely high white cell count.
Analyzers that use myeloperoxidase staining to produce differential counts can measure white blood cells’ expression of the enzyme, which is altered in various disorders.
The complete blood count is interpreted by comparing the reference ranges, which represent the results found in 95% of apparently healthy people.
On average, adult females have lower hemoglobin, hematocrit, and red blood cell count values than males; the difference lessens, but is still present, after menopause.
CBC results for children and newborn babies differ from those of adults.
Newborns’ hemoglobin, hematocrit, and red blood cell count are extremely high to compensate for low oxygen levels in the womb and the high proportion of fetal hemoglobin, which is less effective at delivering oxygen to tissues than mature forms of hemoglobin, inside their red blood cells.
Newborns’ MCV is also increased, and the white blood cell count is elevated with a preponderance of neutrophils.
The red blood cell count and related values begin to decline shortly after birth, reaching their lowest point at about two months of age and increasing thereafter.
The red blood cells of older infants and children are smaller, with a lower MCH, than those of adults.
In the pediatric white blood cell differential, lymphocytes often outnumber neutrophils, while in adults neutrophils predominate.
People living at higher altitudes have higher hemoglobin, hematocrit, and RBC results, and people of African heritage have lower white blood cell counts on average.
Some medical conditions or problems with the blood sample may produce inaccurate results:
Clotted blood is unsuitable for testing, because the platelet count will be falsely decreased and other results may be abnormal.
Samples stored at room temperature for several hours may give falsely high readings for MCV AS red blood cells swell as they absorb water from the plasma; and platelet and white blood cell differential results may be inaccurate in aged specimens, as the cells degrade over time.
Samples drawn from individuals with very high levels of bilirubin or lipids in may show falsely high readings for hemoglobin, because these substances change the color and opacity of the sample, which interferes with hemoglobin measurement.
Some patients produce an antibody that causes their platelets to form clumps when their blood is drawn into tubes containing EDTA, the anticoagulant typically used to collect CBC samples.
Another antibody-mediated abnormality is red blood cell agglutination, red blood cells clumping together because of antibodies bound to the cell surface.
Such red blood cell aggregates are counted as single cells by the analyzer, leading to a markedly decreased red blood cell count and hematocrit, and markedly elevated MCV and MCHC.
These antibodies may be only active at room temperature (cold agglutinins), and the agglutination can be reversed by heating the sample to 37 °C (99 °F).
Samples from people with warm autoimmune hemolytic anemia may exhibit red cell agglutination that does not resolve on warming.
Flow cytometry devices shot beams of light at cells in specific wavelengths and measured the resulting absorbance, fluorescence or light scatter, collecting information about the cells’ features and allowing cellular contents such as DNA to be quantified.
Platelets are technically not cells: they are cell fragments, formed from the cytoplasm of megakaryocytes in the bone marrow.
In its broadest sense, the term flow cytometry refers to any measurement of the properties of individual cells in a fluid stream,[49][50] and in this respect, all hematology analyzers (except those using digital image processing) are flow cytometers. However, the term
Flow cytometry is commonly used in reference to light scattering and fluorescence methods, especially those involving the identification of cells using labelled antibodies that bind to cell surface markers (immunophenotyping).
The Mentzer index, which compares the MCV to the RBC count, can be used to distinguish between iron deficiency anemia and thalassemia.