Hematology is the measurement of elements of the blood. It can be important in the early identification of physical illness or disease.
Variations in the size, shape and number of blood cells can give early insight into the general functioning of blood and the bone marrow where blood is made and clinical factors that may affect it.
The erythrocyte sedimentation rate (ESR) is an easy, inexpensive, nonspecific test that has been used for many years to help detect conditions associated with acute and chronic inflammation, including infections, cancers, and autoimmune diseases. ESR is said to be nonspecific because increased results do not tell the doctor exactly where the inflammation is in the body or what is causing it, and also because it can be affected by other conditions besides inflammation. For this reason, the ESR is typically used in conjunction with other tests.
ESR is helpful in diagnosing two specific inflammatory diseases, temporal arteritis and polymyalgia rheumatica. A high ESR is one of the main test results used to support the diagnosis. It is also used to monitor disease activity and response to therapy in both of these disease.
A peripheral blood smear is often used as a follow-up test to abnormal results on a complete blood count (CBC). It may be used to help diagnose and/or monitor numerous conditions that affect blood cell populations. At one time, a blood smear was prepared on nearly everyone who had a CBC. With the development of more sophisticated, automated blood cell counting instruments, an automated differential is routinely provided. However, if the result from an automated cell count and/or differential indicates the presence of abnormal white blood cells (WBCs), red blood cells (RBCs), and/or platelets or if there is reason to suspect that abnormal cells are present, then a blood smear will be performed. A blood smear examined by a trained eye is still the best method for definitively evaluating and identifying immature and abnormal cells.
A blood smear is often used to categorize and/or identify conditions that affect one or more types of blood cells and to monitor those undergoing treatment for these conditions. There are many diseases, disorders, and deficiencies that can affect the number and type of blood cells produced, their function, and their lifespan. Usually, only normal mature cells are released into the bloodstream, but certain circumstances can induce the bone marrow to release immature and/or abnormal cells into the circulation. When a significant number or type of abnormal cells are present, they can suggest an underlying condition and prompt the doctor to do further testing.
Malaria is an infectious disease caused by Plasmodium parasites. The parasites are spread by the bite of infected female Anopheles mosquitoes. There are four main types of Plasmodium (P) species that infect humans: Plasmodium vivax and Plasmodium ovale, which cause a relapsing form of the disease, and Plasmodium malariae and Plasmodium falciparum, which do not cause relapses. Recently, it was recognized that a fifth species that normally infects macaques, Plasmodium knowlesi, can be naturally transmitted to humans and cases have been seen in parts of Southeast Asia. Rarely, infection can be passed from a woman to her baby during pregnancy or labor and delivery (congenital infection), or transmitted through blood transfusion, organ transplant, or sharing of needles or syringes.
When a human is bitten by an infected mosquito, the parasites enter the blood stream and travel to the liver. After a person is infected, there is usually an incubation period of 7-30 days, after which the parasites enter the person's red blood cells (RBCs). They then multiply inside these cells, which rupture within 48 to 72 hours, causing many of the symptoms of malaria to develop. P. vivax and P. ovale cause relapsing disease as the parasite can stay dormant in the liver before re-entering the blood stream and causing symptoms months, and even years, after the initial infection. While any malaria infection left untreated can cause severe illness and death, infection by P. falciparum is most likely to cause life-threatening disease, as can the newly recognized P. knowlesi.
Most malaria infections and most malaria deaths occur in Africa. Malaria also exists in regions in Central and South America, parts of the Caribbean, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe and the South Pacific. Globally, the World Health Organization (WHO) estimates 3.3 billion people are at risk. In 2008, there were 247 million cases of malaria and nearly one million deaths, the majority of deaths caused by P. falciparum infections in African children.
Cases of malaria in the United States are rare; they mostly occur among those who have travelled to parts of the world where malaria infections are common (endemic).
Glucose-6-phosphate dehydrogenase (G6PD) enzyme testing is used to screen for and help diagnose G6PD deficiencies. It may be used to screen children who experienced persistent jaundice as a newborn that could not be explained by another cause. Currently, newborns are not routinely screened for G6PD deficiency, but it is one of the thirty disorders that are recommended for screening by several organizations, including the March of Dimes.
G6PD testing may also be used to help establish a diagnosis for people of any age who have had one or more unexplained episodes of hemolytic anemia, presence of jaundice, or dark urine. If the person had a recent viral or bacterial illness or was exposed to a known trigger (such as fava beans, a "sulfa" drug, or naphthalene), followed by a hemolytic episode, then G6PD deficiency may be considered.
Repeat G6PD testing may occasionally be ordered to confirm initial findings. In the most common form of G6PD deficiency seen in persons of African ancestry, the G6PD enzyme level is normal in newly produced cells but levels decrease as the red cells age. Because of this, testing is not recommended until after a hemolytic episode resolves. During the episode, a higher percentage of the older more G6PD deficient cells are typically destroyed, leaving the newer, less deficient cells to be tested, potentially masking a G6PD deficiency.
Genetic testing is not routinely done but can be ordered as follow up to an enzyme test that indicates a deficiency to determine which G6PD mutation(s) are present. So far, more than 440 G6PD gene variations have been identified and can cause enzyme activity deficiencies of varying severity depending on the mutation and on the individual person. However, only the most common G6PD mutations are identified during testing. If a specific mutation is known to be present in a family line, tests to detect that particular mutation can also be conducted.
Sickle cell tests are used to identify the presence of hemoglobin S, to evaluate the status and number of the person's RBCs and hemoglobin level, and/or to determine whether a person has one or more altered hemoglobin gene copy. The presence of other abnormal hemoglobin variants may be seen but would require additional testing to identify specifically what type.
There are almost 900 hemoglobin variants of which hemoglobin S is one. To screen for and to confirm the presence of hemoglobin S, a variety of tests have been developed. Some of these may include:
Screening may be performed on family members of an individual who has proven to have sickle cell trait/disease. It also may be done for those who were not screened at birth because universal testing was not yet implemented and who may choose to be tested if their status is not known.
For monitoring treatment:
Particularly in patients with sickle cell disease, the amount of Hb S will be measured and followed over the course of a treatment, for example, after a blood transfusion to ensure that the hemoglobin S level has been reduced.
Other tests that may be used to help evaluate someone who is suspected of having or who is known to have sickle cell trait or disease include:
Hemoglobin variants are abnormal forms of hemoglobin. Made up of heme, an iron-containing portion, and globin, amino acid chains that form a protein, hemoglobin (Hb or Hgb) molecules are found in all red blood cells. They bind oxygen in the lungs, carry the oxygen throughout the body, and release it to the body’s cells and tissues.
Normal hemoglobin types include:
Hemoglobin variants occur when genetic changes in the globin genes cause alterations in the amino acids that make up the globin protein. These changes may affect the structure of the hemoglobin, its behavior, its production rate, and/or its stability. There are four genes that code for alpha globin chains and two genes that code for the beta globin chains. (For general information on genetic testing, see The Universe of Genetic Testing.) The most common alpha-chain-related condition is alpha thalassemia. Its severity is governed by the number of genes affected. (See Thalassemia for more information.)
Beta chain hemoglobin variants are inherited in an autosomal recessive fashion. This means that the person must have two altered gene copies, one from each parent, to have a hemoglobin variant-related disease. If one normal beta gene and one abnormal beta gene are inherited, the person is heterozygous for the abnormal hemoglobin, a carrier. The abnormal gene can be passed on to any offspring, but it does not cause symptoms or health concerns in the carrier.
If two abnormal beta genes of the same type are inherited, the person is homozygous. The person would produce the associated hemoglobin variant and may have some associated symptoms and potential for complications. The severity of the condition depends on the genetic mutation and varies from person to person. A copy of the abnormal beta gene would be passed on to any offspring.
If two abnormal beta genes of different types are inherited, the person is doubly or compound heterozygous. The affected patient would typically have symptoms related to one or both of the hemoglobin variants that he or she produces. One of the abnormal beta genes would be passed on to each offspring.
Several hundred beta chain hemoglobin variants have been documented; however, only a few are common and clinically significant.
There are many other variants. Some are silent – causing no signs or symptoms – while others affect the functionality and/or stability of the hemoglobin molecule. Examples of other variants include: Hemoglobin D, Hemoglobin G, Hemoglobin J, Hemoglobin M, and Hemoglobin Constant Spring, a mutation in the alpha globin gene that results in an abnormally long alpha (α) chain and an unstable hemoglobin molecule. Additional beta chain variant examples are:
Inheritance of one beta S gene and one beta C gene results in Hemoglobin SC Disease. These individuals have a mild hemolytic anemia and moderate enlargement of the spleen. Persons with Hb SC disease may develop the same vaso-occulsive (blood vessel blocking) complications as seen in sickle cell anemia, but most cases are less severe.Sickle Cell – Hemoglobin D Disease.
Individuals with sickle cell – Hb D disease have inherited one copy of hemoglobin S and one of hemoglobin D-Los Angeles (or D-Punjab). These patients may have occasional sickle crises and moderate hemolytic anemia.Hemoglobin E – beta thalassemia.
Individuals who are doubly heterozygous for hemoglobin E and beta thalassemia have an anemia that can vary in severity, from mild (or asymptomatic) to severe.Hemoglobin E – beta thalassemia.
Hemoglobin S – beta thalassemia. Sickle cell – beta thalassemia varies in severity, depending on the beta thalassemia mutation inherited. Some mutations result in decreased beta globin production (beta+) while others completely eliminate it (beta0). Sickle cell – beta+ thalassemia tends to be less severe than sickle cell – beta0 thalassemia. Patients with sickle cell – beta0 thalassemia tend to have more irreversibly sickled cells, more frequent vaso-occlusive problems, and more severe anemia than those with sickle cell – beta+ thalassemia. It is often difficult to distinguish between sickle cell disease and sickle cell – beta0 thalassemia.
Blood typing is used to determine an individual's blood group and what type of blood or blood components the person can safely receive. It is important to ensure that there is compatibility between a person who requires a transfusion of blood or blood components and the ABO and Rh type of the unit of blood that will be transfused. A potentially fatal transfusion reaction can occur if a unit of blood containing an ABO antigen to which a person has an antibody is transfused to that person. For example, people with blood group O have both anti-A and anti-B antibodies in their blood. If a unit of blood that is group A, B, or AB is transfused to this person, the antibodies in the person's blood will react with the red cells, destroying them and causing potentially serious complications.
If an Rh-negative individual is transfused with Rh-positive blood, it is likely that the person will produce antibodies against Rh-positive blood. Although this does not cause problems for the person during the current transfusion, a future transfusion with Rh-positive blood could result in a serious transfusion reaction.
Rh typing is especially important during pregnancy because a mother and her fetus could be incompatible. If the mother is Rh-negative but the father is Rh-positive, the fetus may be positive for the Rh antigen. As a result, the mother’s body could develop antibodies against the Rh antigen. The antibodies may cross the placenta and cause destruction of the baby’s red blood cells, resulting in a condition known as hemolytic disease of the fetus and newborn. To prevent development of Rh antibodies, an Rh-negative mother is treated with an injection of Rh immune globulin during her pregnancy and again after delivery if the baby is Rh-positive. The Rh immune globulin binds to and “masks” any Rh antigen from the fetus that the mother may be exposed to during her pregnancy and delivery and prevents her from becoming sensitized and developing antibodies against the Rh antigen.
Blood typing is also used to determine the blood group of potential donors at a collection facility. Units of blood that are collected from donors are blood typed and then appropriately labeled so that they can be used for people that require a specific ABO group and Rh type.
Antibody identification is used as a follow-up test to a positive indirect antiglobulin test (IAT). The IAT is typically performed during each pregnancy to determine whether the mother has developed any red blood cell (RBC) antibodies and before RBC transfusions as part of a "type and screen" or "type and crossmatch." The antibody identification test is used to determine the RBC antigen(s) that the antibody or antibodies are directed against to determine if they are likely to be clinically significant, i.e., if they are likely to cause a transfusion reaction or hemolytic disease of the newborn (HDN). Some RBC antibodies are known to cause moderate to severe reactions while other less significant ones may cause a positive IAT but few to no symptoms or complications in the blood transfusion recipient or baby.
If one or more clinically significant RBC antibodies are identified, then donor blood that lacks the corresponding RBC antigens must be used for transfusion. When someone has a condition that requires recurrent transfusions, they are exposed to many foreign RBC antigens and may develop multiple RBC antibodies over time, making the process of finding compatible blood increasingly challenging.
An IAT and antibody identification test may be used as part of an investigation if a person has a transfusion reaction. Sometimes an RBC antibody may be present in such a small quantity that it does not cause a positive IAT during pre-transfusion blood compatibility testing. But after the blood is given to the recipient, it can trigger renewed, rapid antibody production and cause a delayed hemolytic transfusion reaction several days later.
If RBC antibodies have been identified in a pregnant woman, then the baby's condition will be monitored. Whether or not the antibodies will affect the baby's condition depends upon the antibody present, the RBC antigens that the fetus has, and when the mother's antibodies come into contact with the fetus's blood. Some antibodies can cross the placenta from mother to baby and cause HDN.
The reticulocyte count is used to help determine if the bone marrow is responding adequately to the body’s need for red blood cells (RBCs) and to help determine the cause of and classify different types of anemia. The number of reticulocytes must be compared to the number of RBCs to calculate a percentage of reticulocytes; so the test is ordered along with a RBC count. A hemoglobin and/or hematocrit are usually ordered in order to evaluate the severity of anemia.
The RBC, hemoglobin, and hematocrit are frequently ordered as part of a complete blood count (CBC). The CBC usually includes an evaluation of RBC characteristics, such as cell size, volume, and shape. Based on these results, a reticulocyte count may be ordered to further examine the RBCs. Reticulocytes can be distinguished from mature RBCs because they still contain remnant genetic material (RNA), a characteristic not found in mature RBCs. Circulating reticulocytes generally lose their RNA within one to two days, thus becoming mature RBCs