Anemia is a condition that occurs when there are too few properly functioning red bloods cells to carry oxygen throughout the body. There are many different causes of anemia. Sickle cell anemia, or sickle cell disease, is a hereditary disorder in which abnormal hemoglobin within the red blood cells interferes with their functioning and survival. Hemorrhage (HEM-or-ij) is significant bleeding that can lead to anemia. Clotting is the process that changes blood into a thick jellylike substance that stops bleeding. Hemophilia is a hereditary disorder in which the blood does not clot normally, leading to excessive bleeding and possibly hemorrhage and anemia.
It was not long before Carrie started to feel lightheaded whenever she stood up. In gym class, she had to stop and rest every five minutes. Noticing Carrie's behavior and how pale she looked, the gym teacher suspected that Carrie had iron-deficiency anemia. This type of anemia is common in teenage girls due to poor eating habits and iron loss from menstruation * . At her coach's suggestion, Carrie visited her doctor. Together they came up with a healthful diet and exercise plan to help Carrie reach an appropriate weight and keep her iron level normal.
Anemia is a condition in which the blood does not contain enough properly functioning red blood cells to carry oxygen to all the cells of the body. There are several dozen types of anemia that fall into three broad categories according to their underlying causes:
Blood contains red and white blood cells, platelets, and plasma—the yellow-tinted portion made up of water and other substances. Erythrocytes are the most abundant cells in the blood and give blood its red color. They are produced from stem cells * in the bone marrow by a process called hematopoiesis (he-ma-tow-po-EE-sis).
As erythrocytes mature in the bone marrow, they fill up with hemoglobin. Hemoglobin consists of four protein chains called globins, and four heme molecules. Heme contains iron that binds to and transports oxygen and carbon dioxide. This characteristic enables hemoglobin to absorb oxygen in the lungs, release oxygen to the cells of the body, and transport carbon dioxide from the cells back to the lungs.
Blood production is a complex process that requires communication among many parts of the body, including the bone marrow, the kidneys, and the spleen. There are many places in the process where something can go wrong. Problems with stem cells, with the production and maturation of erythrocytes, with the manufacture of hemoglobin, with spleen function, and problems caused by improper signaling between the kidney and bone marrow can all lead to anemia. A person can have anemia due to an inherited blood disorder because of an acquired blood condition, or as a side effect of a disease or condition not directly related to the blood. Sometimes anemia can be related to the ingestion of certain medications.
Infection with certain viruses, bacteria, and protozoa * can result in anemia. Deficiencies in nutrients and vitamins such as iron, folate, and Vitamin B12 as well as starvation and malnutrition are also causes of anemia.
Conditions and disorders that can cause low production of erythrocytes leading to anemia include the following:
Hemorrhage, or losing a lot of blood very quickly, can result in anemia because the body cannot make new blood as fast as it is being lost. Hemorrhages can be caused by injury, a burst blood vessel, childbirth, or surgery.
Almost as soon as blood starts to flow from a cut finger or scraped knee, tiny, clear, disk-shaped platelets begin the process of clotting, which entails turning the blood from liquid to solid to stop the flow. Platelets stick together and form a small plug at the point of bleeding. They contain an enzyme (a protein) that causes fibrinogen (fy-BRIN-o-jen), a substance in the blood, to change to fibrin (FY-brin), a hard substance that does not dissolve. The fibrin piles up, helping the platelets to block the opening and stop the blood flow. Fibrin needs other proteins in the plasma, called clotting factors, to do its job. The clotting factors are numbered I through XIII.
Some people have blood that does not clot well. Blood clots can also form in the wrong places and at the wrong time.
Hemophilia is an inherited deficiency in a blood-clotting factor that results in excessive bleeding. For hemophiliacs, losing a tooth or falling off a bicycle can be life-threatening because the bleeding does not stop.
Hemophilia A is a deficiency in clotting factor VIII. Factors I through VII function properly, but then the clotting process is interrupted and blood from a wound continues to flow. Hemophilia B is caused by a deficiency in factor IX.
Hemophilia varies in severity:
Von Willebrand's disease is a common bleeding disorder caused by a deficiency or defect in von Willebrand factor, a protein that helps the blood to clot. Liver disorders can also prevent the blood from clotting well because the liver produces some of the most important clotting factors.
Thrombophilia is the name for any of several inherited disorders in which the blood may clot excessively. Factor V Leiden is the most common form of thrombophilia. Some people with thrombophilia develop blood clots * or thrombosis.
Thrombosis is a condition in which blood clots form in the wrong places, such as in a leg vein. Clots in veins can break free and travel to the heart and lungs, where they can cause a pulmonary embolism * , or blockage, which can be fatal.
Anemia caused by nutritional deficiencies is very common in Africa and Southeast Asia. The World Health Organization estimates that about 1.62 billion people have anemia, including 47.4 percent of all preschool-age children, or approximately 293 million children. The population group with the greatest number of anemic individuals is non-pregnant women (468 million). The highest proportion of individuals affected is in Africa (48–68 percent), while the greatest number affected is in Southeast Asia (315 million). Higher incidence of anemia, particularly iron-deficiency anemia, is more likely to be noted in areas of the world where residents consume little meat in the diet.
The prevalence of anemia in the United States, Canada, and northern Europe is similar, with about 4 percent of men and 8 percent of women affected when hemogloblin * levels are used to estimate prevalence.
Iron-deficiency anemia is very common, especially in infants and teenagers who need a lot of iron to fuel their growing bodies. In addition, 30 to 50 percent of American women are at risk of anemia because of blood loss during menstruation and inadequate amounts of iron in their diets to offset these monthly losses.
In contrast, sickle cell anemia affects millions of people around the world. In some parts of Africa, up to 40 percent of the population has at least one HbS gene. In the United States, about 8 percent of the population has sickle cell disease and 2 million carry the sickle cell trait. It is particularly common in people whose ancestors came from sub-Saharan Africa, Spanish-speaking regions of the Western Hemisphere, Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece, and Italy. One in every 500 African Americans is born with the disease, and one in 12 has a sickle cell trait.
Hemophilia A occurs much more frequently than hemophilia B, with 80 to 85 percent of hemophilia cases classified as hemophilia A. One case of hemophilia B occurs in about every 25,000 to 30,000 male births while hemophilia A affects 1 in every 5,000 males. One-third of those affected with hemophilia A did not report a family history of the disease. According to 2015 estimates, there were approximately 20,000 people in the United States with hemophilia. About 60 percent of all cases of hemophilia are severe, and worldwide about 70 percent of people with hemophilia have no access to treatment.
Von Willebrand's disease is a common bleeding disorder that affects 1 to 2 percent of the U.S. population. Type I, the mildest form of the disease, accounts for 70 percent of cases. Although von Willebrand's disease occurs in both men and women, women are more likely to have symptoms because of heavy bleeding during menstruation and childbirth.
In the United States, 5 to 8 percent of people have some form of thrombophilia, and more than 600,000 Americans are affected by abnormal blood clots. Deep-vein thrombosis affects 200,000 to 400,000 Americans. Almost one-third of them have post-thrombotic syndrome, a chronic disabling condition in the affected limb. In addition, 100,000 to 200,000 Americans have pulmonary embolism, and almost one-third of them die from it.
Iron, folic acid, and vitamin B12 are all required for the bone marrow to make hemoglobin and erythrocytes. If these elements are missing from the diet or are not absorbed by the gastrointestinal tract, anemia can result.
Folate-deficiency anemia can be caused by a diet deficient in fresh fruits and vegetables that contain folic acid. It can also be caused by diseases, alcoholism, or some medications that interfere with the absorption of folate by the body.
Pernicious anemia occurs when individuals do not eat enough foods containing vitamin B12 or are unable to absorb the vitamin properly. To absorb vitamin B12, the lining of the stomach must produce hydrochloric acid and a chemical called intrinsic factor. If acid production is low or intrinsic factor is missing, the vitamin is not absorbed. People with a poor diet, bulimia * , anorexia nervosa * , diabetes, or thyroid disease, or who have had stomach surgery, stomach cancer, or a family history of pernicious anemia, are all susceptible.
Sideroblastic anemia can be an inherited disorder, but it can also be caused by alcoholism, exposure to toxins such as lead, or acquired bone marrow disorders. Thalassemia is an inherited disorder. Diamond-Blackfan anemia has an identifiable inherited genetic defect in about 25 percent of patients.
Aplastic anemia can result from destruction of blood-forming cells by cancer of the bone marrow or exposure to toxic chemicals, radiation, certain antibiotics * , or other medications. In many cases, the cause of aplastic anemia is unknown.
People with kidney diseases often develop anemia because the kidneys no longer produce enough erythropoietin in response to a decrease in red blood cells.
People who are frequently ill with infections are prone to anemia because infection slows the production of red blood cells. Anemia is very common in people with AIDS * because of several factors including high loads of the HIV virus in the bloodstream, low cell counts of normal immune system cells, and due to the negative effects of some of the medications, especially zidovudine (Retrovir), used to treat HIV on red blood cells.
In addition to inherited disorders such as sickle cell disease, there are a variety of other causes of hemolytic anemia. Erythrocytes can be destroyed too soon or too fast for the following reasons:
People with autoimmune diseases * , such as rheumatoid arthritis, can develop hemolytic anemia. In autoimmune diseases, the body's immune system does not work correctly. In addition to destroying foreign cells, such as bacteria that cause infection, the immune system attacks and destroys its own cells, including erythrocytes.
Hemorrhage is any profuse internal or external bleeding from the blood vessels. The most obvious cause of hemorrhage is trauma (injury) to a blood vessel. Hemorrhage can also be caused by aneurysms, weak spots in artery walls that are often present at birth. Over time the blood vessel wall at the site of an aneurysm balloons out and becomes thinner, making it more likely to leak and rupture.
Hypertension, or high blood pressure, is often a contributing factor in brain hemorrhage, which can cause stroke * . Uncontrolled diabetes can weaken blood vessels, especially in the eyes, resulting in a condition called retinopathy (ret-i-NOP-a-thee). Blood vessels can wear out with age. Some medications that affect blood clotting, including aspirin, can increase the likelihood of hemorrhage.
Bleeding disorders such as hemophilia can lead to hemorrhage. Hemophilia is caused by a defective gene that can be passed from mothers to sons via the X chromosome. Female carriers of the hemophilia gene have normal levels of clotting factors. Although a man with hemophilia and a woman who is a carrier can produce a daughter with hemophilia, this combination is very rare. Up to one-third of people with hemophilia have no family history of the disorder. In these cases, a mutation (a change in a gene) has produced a new hemophilia gene, which may be passed on to subsequent generations.
Mild anemia often has no symptoms. Symptoms of more severe anemia depend on various factors, including a person's age, how quickly the anemia developed, and other concurrent illnesses. Symptoms may be more obvious with a rapidly developing anemia. Moderate anemia, such as pernicious anemia that usually develops slowly over a long period of time, may have few noticeable symptoms.
Like Carrie, people with moderate to severe anemia may feel tired, weak, dizzy, and short of breath, which are symptoms caused by the body's cells not getting enough oxygen. This lack of oxygen can also cause irritability and apathy. Sometimes people with moderate to severe anemia appear pale and waxy. Other symptoms may include the following:
Babies born with thalassemia major have severe anemia during the first year of life that results in slow growth, abnormal bone development, and an enlarged liver and spleen. People with thalassemia minor may not have any symptoms.
Visible blood is the most obvious sign of hemorrhage. People with internal hemorrhaging may have no symptoms until complications develop. Symptoms of a brain hemorrhage depend on where the bleeding is occurring and can include the following:
Although hemophilia is present at birth, babies who are not circumcised (a surgical procedure to remove the foreskin of the penis) seldom experience problems until they begin to crawl. Once they start to bump into hard surfaces or fall, they begin to bleed into muscles or joints. This internal bleeding can cause joints to bruise and swell painfully.
Symptoms of von Willebrand's disease include frequent nosebleeds; a tendency to bruise easily; and prolonged bleeding during menstruation, childbirth, or following surgery.
A complete blood count (CBC) is used to test for anemia. A small sample of blood is drawn, and the numbers and volume of the different types of blood cells and the hemoglobin content of the red blood cells are measured. Some of the blood is smeared onto a slide, and the color, size, and shape of the red blood cells are observed under a microscope. Iron-deficiency anemia is characterized by small red blood cells. Folate-deficiency and pernicious anemias are characterized by large red blood cells.
Sickle cell anemia and sickle cell trait can be diagnosed by a test called hemoglobin electrophoresis (e-lek-tro-fo-REE-sis), which detects the presence of hemoglobin S and other abnormal hemoglobins.
Anemia is often caused by problems in the bone marrow where blood cells are made. Sometimes it is necessary to take a bone marrow sample to determine the cause of the anemia. A needle is inserted into the hip bone, and a sample of marrow is withdrawn and analyzed.
Even though it might be easy to determine whether a patient is anemic, finding the underlying cause can be more difficult. Anemia can be a symptom of many different diseases and disorders, and treatment depends entirely on the cause. Individual and family medical histories, symptoms, diet, illnesses, and drugs and medications are all important elements in diagnosing the cause of anemia. Treatment is specific for each type of anemia and is based on treating the underlying deficiency or disease.
Erythropoietin is sometimes administered to increase the production of red blood cells in anemia caused by cancer, AIDS, kidney disease, or rheumatoid arthritis. Other drugs are used to stimulate red blood cell production in people with some types of thalassemia or sickle cell anemia. Sometimes drugs that reduce the activity of the immune system (immunosuppressives) are used to treat hemolytic anemia caused by autoimmune disease. Occasionally, the spleen must be removed to stop the premature destruction of erythrocytes.
Aplastic anemia is sometimes treated with a bone marrow transplant from a relative with compatible cell types. It can be difficult to find a transplant donor with the right cell type.
There is no cure for sickle cell anemia. Treatment is preventive and directed at symptoms:
In addition to the symptoms and complications of anemia, people with sickle cell anemia periodically experience bouts of critical illness called crises. Sickle-shaped red blood cells clump more easily than normal red blood cells. Sickle cell crises begin suddenly when clumping of sickled red blood cells in the blood vessels obstructs the normal flow of blood, depriving tissues and organs of oxygen. The first crises usually appear in early childhood.
Crises can be brought on by respiratory infection, loss of body fluids from vomiting or diarrhea, or situations in which the body's need for oxygen is increased. They may occur for no obvious reason. A crisis can last for several days, and cause fever and sharp intense pain in the back, abdomen * , chest, arms, and legs. In infants, the hands and feet may become swollen and painful.
Crises can damage almost any part of the body, but especially the bones, kidneys, intestines, lungs, liver, spleen, and the central nervous system * , including the brain. Crises can also damage the eyes and cause stroke, convulsions * , or paralysis.
People with sickle cell anemia are more susceptible to all kinds of bacterial and fungal infections. They are more likely to experience kidney failure and liver problems. By 30 years of age, about 70 percent of people with sickle cell anemia have developed gallstones.
Sometimes anemia is caused by chronic bleeding, such as from a wound in the skin or mucous membranes inside the body (ulcer). The source of bleeding must first be found and treated. Iron supplements are often needed to help boost hemoglobin production. In severe cases, a blood transfusion is used to replenish the volume of blood in the body.
When bleeding is visible, the cause of the hemorrhage is obvious. Blood tests and spinal fluid tests can reveal evidence of brain hemorrhage. Computed tomography (CT or CAT) scanning is an important imaging technique for detecting bleeding in the brain and other tissues.
The first goal in treating a hemorrhage is to stop the bleeding. Hemorrhage caused by trauma or the tearing of blood vessels can be treated by clamping or surgically repairing the tears. Hemorrhage resulting from vessel leakage due to high blood pressure can be treated with medicines to reduce blood pressure, prevent vessel spasm, and reduce pain. Surgery may be needed to reduce the pressure of blood that has collected in the brain. Blood factors to help the blood clot may be administered to those with bleeding disorders.
If the blood loss is life-threatening, a blood transfusion is necessary. In less severe cases, the body itself can slowly bring the blood volume and hemoglobin content back to normal. In fact, people can survive the loss of two-thirds of their blood volume over a 24-hour period.
Hemophilia can be diagnosed by measuring the levels of clotting factors in the blood. DNA testing (direct analysis of the genes) can determine whether a woman carries a gene for hemophilia. Tests can be performed on fetuses to determine whether they have inherited hemophilia. Mild cases of hemophilia may not be diagnosed until adulthood, when unexplained and excessive bleeding accompanies surgery or a visit to the dentist. Likewise von Willebrand's disease often goes undiagnosed or is misdiagnosed.
Those with hemophilia are often supplied with the missing blood-clotting factor. These factors are collected, purified, and combined from the blood donations of many people. Since the mid-1990s, the factors have been produced by genetic engineering, which does not require blood donations. The clotting factors are transfused through a person's vein at a hospital, doctor's office, or by a properly trained individual at home.
People with mild cases of hemophilia may never or only rarely need transfusions. With a major injury or surgery, a person with hemophilia may need transfusions two or three times per day for days or weeks. Some people with severe hemophilia may get transfusions on a regular basis as a preventive measure.
A medication called desmopressin (DDAVP) can sometimes help release any extra stores of factor VIII in people with mild or moderate hemophilia A or von Willebrand's disease. This is a temporary treatment that may help avoid a transfusion after a minor injury.
People with hemophilia bruise easily, but skin bruises are rarely serious. Bleeding from small cuts and scrapes can usually be stopped by applying firm pressure to the area for several minutes. Deep cuts may bleed profusely and require treatment.
Joint bleeding is a serious complication of hemophilia. Prompt treatment is necessary to prevent severe pain and swelling, and joint bleeding can lead to arthritis (inflammation of the joints), deformity, and disability. Boys with hemophilia often learn to recognize joint bleeding as a tingling sensation before the pain or swelling occurs.
Bleeding into a muscle, most often the calf, thigh, or forearm, commonly occurs simultaneously with or following an injury. The resulting swelling, which can develop over several days, may create pressure inside the muscles and damage nerves and blood vessels. Symptoms include muscle tightness, pain, a change in skin temperature, and tingling or numbness. Early treatment is needed to prevent permanent immobility or paralysis.
Any type of neck or head injury can be extremely dangerous for the person with hemophilia. Neck and throat hemorrhages can obstruct breathing. Head injury, even a minor fall or bump on the head, can cause bleeding into the brain. Symptoms include irritability, headache, nausea, vomiting, double vision, and confusion.
Some people with thrombophilia or thrombosis need treatment only during pregnancy; when recovering from surgery; or when sitting for long periods of time in a car or airplane. Other people need to take anticlotting medication for their entire lives.
The long-term effect of anemia is to put stress on the heart, which must work harder to pump more blood through the body. Over time, the heart enlarges, increasing the risk of heart attack and heart failure.
Good nutrition plays a big part in preventing or treating many types of anemia. Maintaining a healthful diet requires eating foods on a daily basis that include the following:
Many people with sickle cell anemia go through long periods of remission * during which they may feel relatively well, engage in most normal activities, and are free of crises. Other people experience pain on a daily basis, and some are hospitalized with crises several times per year.
In the United States, babies are tested for hemoglobin S as part of routine newborn screening regardless of ethnic background. Prenatal testing, or testing of the fetus while the mother is still pregnant, is also available. Before this screening became commonplace, many babies with sickle cell anemia died from infections in infancy. The use of preventive antibiotics significantly reduced this infant mortality. Children with sickle cell anemia receive a complete set of immunizations.
Daily folic acid may stimulate new red blood cell production. Fluid intake is important to prevent the dehydration of cells that increases their sickling. Lifestyle habits that can help sickle cell patients stay healthy and have fewer crises include:
Prospective parents who might be carrying the HbS gene may choose to be tested and receive genetic counseling before having children.
As soon as a child is diagnosed with hemophilia, parents should try to prevent or reduce occurrences of bleeding. The children should have soft toys without sharp corners and padded clothing, particularly at the elbows and knees, while learning to walk. Children should be immunized, but the injections should be given under the skin rather than into the muscle to prevent hemorrhage. Children should clean their teeth regularly and visit the dentist to prevent tooth decay and gum disease * , which can lead to bleeding episodes.
Hemophilia is usually not fatal, and people often live long and active lives with the disorder. Activities such as swimming, walking, and bicycling can help build up muscles that support the joints. Contact sports such as football or wrestling, however, are prohibited because of the high risk of head or neck injury. People with hemophilia should never take aspirin because it increases the tendency to bleed and interferes with clotting.
See also AIDS and HIV Infection • Autoimmune Disorders: Overview • Bruises • Bulimia Nervosa and Binge Eating Disorder • Chronic Illness • Dietary Deficiencies • Eating Disorders: Overview • Embolism • Fainting (Syncope) • Genetic Diseases: Overview • Hemoglobinopathies • Hypertension • Intracranial Bleeding • Malnutrition • Nosebleeds • Seizures • Sickle Cell Anemia • Stroke • Thalassemia
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Mann, Sabrina A. Broken Blood: A Reflection of Loss and Hope in the Hemophilia Community. Self-published, 2015.
Walker, Kristin. My Daughter's Journey with Sickle Cell Disease. New York: Heavenly Minded Productions, 2014.
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* menstruation (men-stroo-AYshun) is the discharge of the blood-enriched lining of the uterus. Menstruation normally occurs in females who are physically mature enough to bear children. Most girls have their first period between the age of 9 and 16 years. Menstruation ceases during pregnancy and after menopause. Because it usually occurs at about four-week intervals, it is often called the monthly period.
* genes are chemicals inherited from both parents that help determine physical characteristics, such as whether a person has brown hair or blue eyes, or in this case, normal or abnormal hemoglobin.
* stem cell an unspecialized cell that gives rise to differentiated cells.
* protozoa (PRO toe zO ah) are a group of microscopic, singlecelled organisms capable of causing infection in humans.
* blood clots are thickenings of the blood into a jellylike substance that helps stop bleeding. Clotting of the blood within a blood vessel can lead to blockage of blood flow.
* pulmonary embolism is a blockage of the pulmonary artery or one of its branches that is frequently caused by thrombosis, or formation of a blood clot, in the lower extremities.
* hemoglobin (heme O GLO bun) is the protein responsible for carrying oxygen molecules in the blood.
* bulimia (bu-LEE-me-a) is an eating disorder in which a person has episodes of out-of-control overeating, or binges, and then tries to make up for them by making themselves vomit, by taking laxatives, or by exercising to excess to avoid gaining weight.
* anorexia nervosa (an-o-REKse- a ner-VO-sa) is an emotional disorder characterized by dread of gaining weight, leading to selfstarvation and dangerous loss of weight and malnutrition.
* antibiotics (an-tie-by-AH-tiks) are drugs that kill or slow the growth of bacteria.
* AIDS or acquired immunodeficiency (ih-MYOO-no-dih- FIH-shen-see) syndrome is an infection that severely weakens the immune system; it is caused by the human immunodeficiency virus (HIV).
* autoimmune diseases (awtoh- ih-MYOON) are diseases in which the body's immune system attacks some of the body's own normal tissues and cells.
* stroke is a brain-damaging event usually caused by interference with blood flow to the brain. A stroke may occur when a blood vessel supplying the brain becomes clogged or bursts, depriving brain tissue of oxygen. As a result, nerve cells in the affected area of the brain, and the specific body parts they control, do not properly function.
* dehydration (dee-hi-DRAY-shun) is a condition in which the body is depleted of water, usually caused by excessive and unre-placed loss of body fluids, such as through sweating, vomiting, or diarrhea.
* blood transfusion is the process of giving blood (or certain cells or chemicals found in the blood) to a person who needs it due to illness or blood loss.
* abdomen (AB-do-men), commonly called the belly, is the portion of the body between the thorax (THOR-aks) and the pelvis.
* central nervous system (SEN-trul NER-vus SIS-tem) is the part of the nervous system that includes the brain and spinal cord.
* convulsions (kon-VUL-shuns), also called seizures, are involuntary muscle contractions caused by electrical discharges within the brain and are usually accompanied by changes in consciousness.
* remission is an easing of a disease or its symptoms for a prolonged period.
* gum disease is an infection caused by bacteria that affect the tissues surrounding and supporting the teeth.