Hemolytic anemia is a rare form of anemia in which red blood cells (erythrocytes) are destroyed and removed from the bloodstream before their usual lifespan is up. Healthy red blood cells usually live about 120 days (4 months) in the bloodstream before the body removes them. In hemolytic anemia, the body breaks down and removes red blood cells faster than it can replace them. (The breakdown of red blood cells is called hemolysis).

 

Anemia

The term "anemia" means that the number of red blood cells in a person's blood is less than normal or the red blood cells don't contain enough hemoglobin. Hemoglobin is an iron-rich protein in red blood cells that gives blood its red color. Anemia is also known as having a "low blood count."

 

The most common symptom of anemia is fatigue (tiredness). Fatigue develops because the tissues of the body don't receive enough oxygen. The hemoglobin in red blood cells picks up oxygen in the lungs and circulates it to the tissues of the body. If there aren't enough red blood cells, or not enough hemoglobin in the red blood cells, the blood can't carry enough oxygen to the rest of the body.

 

Red blood cells also are called RBCs or erythrocytes. Normal red blood cells are all about the same size and look like tiny doughnuts without holes in the center. Normal red blood cells have an average lifespan of 120 days, after which they die and are removed from the bloodstream. The iron in the hemoglobin is recycled to make new red blood cells. The marrow inside the large bones of the body continually produces new red blood cells to replace the ones that have died.

 

The blood also contains two other types of cells: white blood cells (leukocytes) and platelets. White blood cells help fight infection. Platelets help blood to clot. In some kinds of anemia, there are low amounts of all three types of blood cells.

 

There are three main causes of anemia: blood loss, lower than normal levels of red blood cell production, or higher than normal rates of red blood cell destruction. More than one of these factors can combine to cause anemia.

 

Hemolytic anemia

Hemolytic anemia is due to increased hemolysis (destruction) of red blood cells. The bone marrow increases production of red blood cells to replace the hemolyzed blood cells, but it can't produce them fast enough to meet the body's needs.

 

In some types of hemolytic anemia, the body makes abnormal red blood cells that break down and hemolyze on their own. In other types of hemolytic anemia, the body's immune system, infections, certain drugs, or other agents attack normal red blood cells, causing them to hemolyze. The hemolysis can occur in the bloodstream or in an organ called the spleen.

 

The two main types of hemolytic anemia are inherited and acquired. In inherited hemolytic anemia, the condition is passed from parent to child. In acquired hemolytic anemia, the person develops the condition from some other cause. Hemolytic anemia can begin rapidly or come on gradually and can range from mild to severe.

 

Outlook

Hemolytic anemia can often be successfully treated or controlled. The course of hemolytic anemia depends on the cause and the severity of the anemia. Mild hemolytic anemia may need no treatment at all. Severe hemolytic anemia can be life threatening if it's not treated.

 

If you have an inherited form of hemolytic anemia, it's a lifelong condition that requires ongoing treatment. If your anemia is caused by an infection or use of a particular medicine, the anemia may go away when the infection is treated or when the medicine is stopped.

 

Types of hemolytic anemia

There are many types of hemolytic anemia. Some types are inherited, which means a person is born with them. Other types are acquired, which means they develop in response to some other disease or factor.

 

Inherited types

In the inherited hemolytic anemias, one or more of the genes that control the production of red blood cells are defective, causing the bone marrow to make abnormal cells. The red blood cell abnormality can involve the cell membrane (the outer covering of the cell), the chemistry inside the cell, or the production of abnormal types or amounts of hemoglobin. The abnormal cells may be fragile and break down (hemolyze) on their own while circulating in the bloodstream. Also, the body's immune system may recognize that the red blood cells are abnormal, and an organ called the spleen may remove the cells from the bloodstream.

Sickle cell anemia

In sickle cell anemia, the body makes an abnormal type of hemoglobin. This hemoglobin causes the red blood cells to take on an abnormal shape. Instead of their normal shape (a doughnut without a hole) the red blood cells can turn into a sickle (crescent) shape. Sickle cells die and are removed from the bloodstream prematurely. In the United States, sickle cell anemia occurs most often in African Americans. There also are other types of abnormal hemoglobin that can cause hemolysis.

Thalassemia

The thalassemias are a group of anemias in which the body doesn't make enough of certain types of hemoglobin. This leads to abnormal red blood cells that die and are removed from the body prematurely. Thalassemia is most common among people of Mediterranean, African, or Southeast Asian descent.

Hereditary spherocytosis

In hereditary spherocytosis, an abnormality of the surface membrane of red blood cells causes them to take on a spherical (ball) shape. The abnormally shaped blood cells have a short lifespan. Hereditary spherocytosis is the most common cause of hemolytic anemia among people whose ancestors come from Northern Europe.

Hereditary elliptocytosis (ovalocytosis)

Hereditary elliptocytosis is another condition involving the cell membrane. It's also known as hereditary ovalocytosis. In this condition, the red blood cells are elliptic (oval) in shape and not as flexible as normal red blood cells. These abnormal red blood cells also have a short lifespan.

Glucose-6-phosphate dehydrogenase deficiency

In glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), the red blood cells are missing an important enzyme called G6PD. G6PD is part of the normal chemistry inside red blood cells. In G6PD deficiency, if red blood cells come into contact with certain substances in the bloodstream, the missing enzyme causes the cells to rupture and die prematurely. The hemolysis can be triggered by the person taking sulfa or antimalaria medicines, eating fava beans, or having an infection. G6PD deficiency mostly affects males of African or Mediterranean descent. It affects about 1 in 10 African American males.

Pyruvate kinase deficiency

Pyruvate kinase also is an enzyme-deficiency hemolytic anemia in which the missing enzyme is called pyruvate kinase. Not having enough of this enzyme causes red blood cells to break down easily. This disorder is more common among the Amish than other groups.

 

Acquired types

In acquired types of hemolytic anemia, the red blood cells may be normal, but some other disease or factor causes the body to destroy the red blood cells and remove them from the bloodstream. The destruction of the red blood cells can occur in the bloodstream or, more commonly, in the spleen.

Immune hemolytic anemia

In immune hemolytic anemia, the body's immune system destroys the body's red blood cells. There are three main types of immune hemolytic anemia: autoimmune, alloimmune, and drug-induced.

 

Autoimmune hemolytic anemia. In autoimmune hemolytic anemia (AIHA), a person's immune system mistakenly produces antibodies directed against the person's own red blood cells. One-half of all cases of hemolytic anemia are AIHA. The cause of AIHA is unknown. It may come on very quickly and become serious. It's most common in people over age 40.

 

Having certain diseases or infections can make a person more likely to develop AIHA. These include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and other blood cancers; Epstein-Barr virus (which causes infectious mononucleosis); cytomegalovirus (a virus that infects cells); mycoplasma pneumonia (a lung infection); hepatitis; and human immunodeficiency virus (HIV).

 

In some types of AIHA, the antibodies produced by the body are called warm antibodies. This means they are active (that is, they destroy red blood cells) at warm temperatures, such as body temperature. In other types of AIHA, the body produces "cold-reactive antibodies," which means they become active when exposed to colder temperatures. Cold-reactive antibodies can become active when the body (typically the hands or feet) is exposed to temperatures of less than 32–50°F (0–10°C). Warm antibody AIHA is more common than cold-reactive antibody AIHA.

 

Alloimmune hemolytic anemia. In alloimmune hemolytic anemia, antibodies are produced against the red blood cells a person receives in a blood transfusion. If the blood type used for the transfusion is different than the recipient's blood type, the recipient's immune system can develop antibodies that attack and destroy the transfused blood cells.

 

Alloimmune antibodies also can develop as a result of the mixing of blood between a pregnant woman and her baby at delivery. If the mother's blood type is Rh-negative and the baby's is Rh-positive, the mother can produce antibodies against the baby's blood type. If a mother develops anti-Rh antibodies as a result of one pregnancy, they can cross the placenta during the next pregnancy and harm the fetus. To prevent this, a medicine called RhoGam can be given at the time of delivery to block the mother's body from developing antibodies against the baby's blood type.

 

Drug-induced hemolytic anemia. Certain drugs can cause a reaction that develops into hemolytic anemia. These drugs include high doses of penicillin and related drugs, acetaminophen, quinine and other drugs to treat malaria, anti-inflammatory drugs, and levodopa.

Mechanical hemolytic anemias

Physical damage to red blood cell membranes can result from microangiopathic changes in small blood vessels. An artificial heart valve or other device used in blood vessels also can damage red blood cell membranes. Damage can occur with a heart-lung bypass machine during open-heart surgery. Damage also can occur with preeclampsia or eclampsia (elevated blood pressure and protein in the urine after the 20th week of pregnancy). Blood cell damage may occur in the limbs while participating in marathons or other strenuous activities.

Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder in which the red blood cells are abnormal due to a lack of certain proteins. The body destroys these cells more rapidly than normal. The destruction may occur continuously at a low level and flare up at times (paroxysmal). People with PNH are at increased risk for blood clots in the veins and low levels of white blood cells and platelets.

Other causes of damage to red blood cells

Infections and other agents can invade and damage red blood cells. Malaria and "blackwater fever," tick-borne diseases, snake venom, and toxic chemicals can attack and destroy red blood cells, causing hemolytic anemia.

 

Causes

There are many different types of hemolytic anemia. The immediate cause of hemolytic anemia is the early destruction (hemolysis) of red blood cells. The factors that cause early hemolysis can be inherited or acquired. Sometimes, the cause of early hemolysis is not known.

 

Causes of inherited hemolytic anemia

In inherited hemolytic anemias, there is a problem with the genes that control the production of red blood cells. People with an inherited hemolytic anemia received a defective red blood cell gene from one (or both) of their parents. Different types of defective genes account for the different types of inherited hemolytic anemias. In each of the types of inherited hemolytic anemia, the body produces abnormal red blood cells. The red blood cell abnormality can involve the cell membrane (the outer covering of the cell), the chemistry inside the cell, or the production of abnormal hemoglobin.

 

Causes of acquired hemolytic anemia

In acquired types of hemolytic anemia, the body produces normal red blood cells, but some disease or other factor destroys the cells prematurely. The destruction of red blood cells can be caused by an immune disorder, infection, reaction to a medicine, or reaction to a transfusion. The early destruction of cells usually occurs in the spleen or the bloodstream. The spleen is an organ in the upper left part of the abdomen that helps remove abnormal blood cells from the bloodstream.

 

Who is at risk

Hemolytic anemia can affect people of all ages and both genders. Most types of hemolytic anemia are equally common in men and women and can develop at any age. Autoimmune hemolytic anemia is slightly more likely in women over age 40. Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is more common among males. People of all races can develop hemolytic anemia. Some types of hemolytic anemia are more likely to occur in certain populations than others.

 

In the United States, sickle cell anemia, one of the most common forms of hemolytic anemia, occurs primarily among African Americans. G6PD deficiency affects males of African or Mediterranean descent. About 1 in 10 African American men have G6PD deficiency.

 

Signs and symptoms

Signs and symptoms of hemolytic anemia depend on the type of anemia and its severity. People with mild hemolytic anemia often have no symptoms. However, if the anemia is severe, the symptoms increase and become more serious. Many of the signs and symptoms of hemolytic anemia apply to all anemias.

 

Signs and symptoms of anemia

The most common symptom of all types of anemia, including hemolytic anemia, is fatigue (tiredness). Fatigue is caused by having too few red blood cells to carry oxygen to the body. This lack of oxygen in the body can cause you to feel weak or dizzy, have a headache, feel short of breath, or even pass out when changing position (for example, standing up).

 

Since the heart must work harder to circulate the reduced amount of oxygen in the blood, signs and symptoms of anemia may also include a fast or irregular heartbeat or a heart murmur.

 

People with anemia may have pale skin, tongue, gums, and nail beds due to the low levels of hemoglobin.

 

Signs and symptoms of hemolytic anemia

The signs and symptoms associated with hemolytic anemia include:

Jaundice. This is a yellowish discoloration of the skin and eyes. When red blood cells die, they release their hemoglobin into the bloodstream. The hemoglobin is broken down by the body into a compound called bilirubin, which gives the skin and eyes the yellowish color seen in jaundice. It also causes the urine to be dark yellow or brown

Pain in the upper abdomen due to gallstones or an enlarged liver. If you have high levels of bilirubin and cholesterol (from the breakdown of red blood cells), they can form into stones in the gallbladder, which can become painful.

Leg ulcers and pain. In people with sickle cell anemia, the abnormal cells can clog small blood vessels, blocking blood flow. This can cause leg sores and pain in different parts of the body.

A severe reaction to blood transfusion. Signs and symptoms of a transfusion reaction include fever, chills, low blood pressure, and shock (a life-threatening condition that occurs when the body isn't getting enough blood flow).

 

Diagnosis

Hemolytic anemia is diagnosed using a combination of medical and family history, physical exam, and diagnostic tests.

 

Specialists involved

Primary care doctors, such as a family doctor or pediatrician, may be involved in diagnosing and treating hemolytic anemia. Other kinds of doctors involved include:

A hematologist (blood disease specialist)

A cardiologist (heart specialist)

 

Doctors and clinics that specialize in treating inherited blood disorders, such as sickle cell anemia and thalassemia, may be involved. If you have an inherited form of hemolytic anemia, you may want to consult a genetics counselor.

 

Medical and family history

To determine the cause and severity of hemolytic anemia, your doctor may ask detailed questions about your symptoms, personal medical history, and your family medical history. You may be asked whether you or anyone in your family has had problems with anemia in the past. Your doctor will want to know what illnesses or conditions you have had recently and what medicines you take.

 

You also may be asked whether you have been exposed to any drugs or chemicals or have an artificial heart valve or device that could damage red blood cells.

 

Physical exam

Your doctor will perform a physical exam to determine how severe the anemia is and to check for possible causes. This exam may include:

Checking for jaundice (yellowish skin and eyes)

Listening to your heart for a rapid or abnormal heartbeat

Listening for rapid or uneven breathing

Feeling your abdomen to check the size of your liver and spleen

Performing a pelvic and rectal exam to check for internal bleeding

 

Diagnostic tests and procedures

Your doctor may perform a number of tests, including the following:

 

Blood tests

 

Complete blood count. Usually, the first test used to diagnose anemia is a complete blood count (CBC). The CBC tells a number of things about a person's blood, including:

The hemoglobin level. Hemoglobin is the iron-rich protein in red blood cells that carries oxygen through the body. The normal range of hemoglobin levels for the general population is 11-15 g/dL. A low hemoglobin level means a person has anemia.

The hematocrit level. The hematocrit level measures how much of the blood is made up of red blood cells. The normal range for hematocrit levels for the general population is 32-43%. A low hematocrit level is another sign of anemia.

 

The normal range of these levels may be different in certain racial and ethnic populations. Your doctor can explain your individual test results.

 

The CBC also checks:

The number of red blood cells. Too few red blood cells means a person has anemia. A low number of red blood cells is usually seen with either a low hemoglobin or a low hematocrit level, or both.

Red blood cell size. The mean cell volume measures the average size (volume) of red blood cells. Red blood cells can be normal sized, smaller, or larger, depending on the type of anemia.

The number of white blood cells. White blood cells are involved in fighting infection

The number of platelets. Platelets are small cells that are involved in blood clotting.

 

Additional blood tests. If the CBC results confirm you have anemia, your doctor may order additional blood tests to determine the type and cause of the anemia. Some of the tests that can be used in the diagnosis of hemolytic anemia include:

Reticulocyte count. Reticulocytes are young red blood cells. The reticulocyte count measures the rate at which the bone marrow is producing new red blood cells. Typically in hemolytic anemia, the reticulocyte count is higher than normal because the bone marrow is working overtime to replace the destroyed red blood cells.

Peripheral smear. This test involves looking at the blood cells through a microscope. Some types of hemolytic anemia involve abnormally shaped red blood cells, which can be seen through a microscope.

Coombs' test. The Coombs' test measures the presence of antibodies directed against red blood cells.

Haptoglobin, bilirubin, and liver function tests. When red blood cells break down, they release their hemoglobin into the bloodstream. The hemoglobin combines with a chemical called haptoglobin. A low level of haptoglobin in the bloodstream is an indication of hemolytic anemia. Bilirubin comes from the breakdown of hemoglobin. High levels of bilirubin cause jaundice, a yellowish discoloration to the skin and eyes. High levels of bilirubin in the blood occur with the hemolysis of red blood cells, and also with some liver and gallbladder diseases. Liver function tests help to determine whether high bilirubin levels are from hemolytic anemia or liver/gallbladder disease.

Hemoglobin electrophoresis. This test detects abnormal hemoglobin, which is the cause of some types of hemolytic anemia.

Testing for paroxysmal nocturnal hemoglobinuria (PNH). In PNH, the red blood cells are missing certain proteins. The test for PNH looks for red blood cells that are missing these proteins.

Osmotic fragility test. This test looks for abnormally fragile red blood cells, which are seen in hereditary spherocytosis.

Testing for glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency. This test, called a rapid fluorescent spot test, detects evidence of G6PD enzyme activity in a sample of blood.

 

Bone marrow tests

In some cases, the doctor may want to examine the cells of the bone marrow under a microscope. A sample of bone marrow can be obtained with either a bone marrow biopsy or aspiration. A bone marrow biopsy is a minor surgical procedure to remove a small amount of bone marrow tissue. For a bone marrow aspiration, your doctor removes a small amount of bone marrow fluid through a needle.

Tests for other causes of anemia

Because anemia has many causes, the doctor may order tests for conditions such as:

Kidney failure

Lead poisoning

Low levels of vitamins, including vitamin B12, vitamin C, and folate

Iron deficiency

 

Treatment

 

Goals of treatment

The goals of treating hemolytic anemia are to reduce or stop the hemolysis of red blood cells, to increase the red blood cell count to normal levels, and to treat the underlying cause.

 

The treatment you receive will depend on the type, cause, and severity of the hemolytic anemia you have. Your age, overall health, and medical history also will be considered. If you have an inherited form of hemolytic anemia, it's a lifelong condition that may require ongoing treatment. If you have an acquired hemolytic anemia, the anemia may go away if the underlying cause can be found and corrected.

 

Who needs treatment

Severe hemolytic anemia usually requires ongoing treatment and can be life threatening if left untreated. A person with mild hemolytic anemia may not need treatment as long as the condition doesn't get worse.

 

Types of treatment

Treatments for hemolytic anemia include blood transfusion, medicines, lifestyle changes, plasmapheresis (treatment to remove antibodies from red blood cells), surgery, and bone marrow or stem cell transplant.

 

Blood transfusions

Blood transfusions are used to treat severe or life-threatening anemia. Transfusions are given through a vein and require careful matching of donated blood with the recipient's blood. The transfused blood must be compatible with the recipient's blood type (for example, type A, Rh-negative). People who receive blood transfusions on a regular basis must be monitored and treated for a buildup of too much iron in the body.

 

Medicines

Some types of hemolytic anemia, particularly autoimmune hemolytic anemia (AIHA), can be improved with medicines. Corticosteroid medicines, such as prednisone, can be used to suppress the immune response against red blood cells. If there is no response to corticosteroids, other drugs that suppress the immune system, such as azathioprine, cyclophosphamide, or danazol, may be prescribed.

 

Intravenous (IV) gamma globulin may also be given to suppress antibody formation if the person does not respond to corticosteroids. Rituximab is being tried experimentally for AIHA. This drug reduces hemolysis by suppressing the immune system cells that produce the antibodies against red blood cells. An experimental medicine called eculizumab is being studied as a treatment for paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab is an antibody directed against part of the immune system that is involved in PNH.

 

Plasmapheresis

Plasmapheresis removes antibodies from red blood cells. It may help if other treatments for immune hemolytic anemia don't work.

 

Surgery

In some cases of hemolytic anemia, it's necessary to surgically remove the spleen. The spleen is an organ in the upper left part of the abdomen that helps remove abnormal red blood cells from the bloodstream. The spleen also can contribute to some types of hemolytic anemia. An enlarged or diseased spleen removes more red blood cells than normal, causing anemia. Removal of the spleen may be necessary to stop or reduce high rates of red blood cell destruction.

 

Bone marrow or stem cell transplant

Hemolytic anemia that results from the failure of bone marrow to make normal red blood cells (such as in thalassemia) is sometimes treated with bone marrow or stem cell transplants. Donor marrow is usually taken from a large bone, such as the pelvis. Marrow is given by transfusion through a vein. Stem cells for a transplant can be from matched umbilical cord blood, from bone marrow donated by a family member, or from a matched but unrelated donor. Stem cells in bone marrow develop into mature blood cells.

 

Lifestyle changes

For people with AIHA with cold-reactive antibodies, avoiding exposure to cold temperatures can help prevent hemolysis of their red blood cells. It's especially important to protect the fingers, toes, and ears from the cold. Typical ways to protect from cold include:

Wear gloves or mittens when taking food out of the refrigerator or freezer.

Wear a hat, scarf, and a coat with snug cuffs during cold weather.

Turn down air conditioning or dress warmly while in an air conditioned space.

Warm up the car before driving in cold weather.

 

People born with glucose-6-phosphate dehydrogenase deficiency can prevent the development of anemia by avoiding substances that can trigger hemolysis, such as fava beans and certain medicines.

 

Prevention

Hemolytic anemia can't be prevented in people who are born with the genes for inherited types of hemolytic anemia. One exception is glucose-6-phosphate dehydrogenase (G6PD) deficiency. A person born with G6PD deficiency can prevent the development of anemia by avoiding substances, such as fava beans and certain medicines, which can trigger hemolysis.

 

Transfusion reactions, which can cause hemolytic anemia, can be prevented by ensuring a match of the blood types between the donor and recipient. When a pregnant woman has Rh-negative type blood and her fetus has Rh-positive type blood, a medicine called RhoGam given at the time of delivery can block the mother's body from developing antibodies against the baby's blood type.

 

Living with hemolytic anemia

The course of hemolytic anemia depends on the cause and the severity of the anemia. Mild hemolytic anemia may need no treatment at all. If you have an inherited form of hemolytic anemia, it is a lifelong condition that may require ongoing treatment. If the anemia is caused by a medicine or infection, the anemia may go away when the medicine is stopped or the infection is cured.

 

Ongoing health care needs

If you have hemolytic anemia, taking care of your overall health is important. See your doctor regularly for checkups and follow your treatment plan. Get a flu shot every year, and ask your doctor about the vaccine to prevent pneumoccal pneumonia.

 

Be sure to get plenty of rest. Stay away from cold temperatures if you have cold-reactive antibody autoimmune hemolytic anemia. During cold weather, wear a hat, scarf, and a warm coat. When taking cold food out of the refrigerator or freezer, wear gloves. Turn down air conditioning or dress warmly while in an air conditioned space, and warm up the car before driving in cold weather.

 

If you have glucose-6-phosphate dehydrogenase deficiency, avoid taking sulfa or antimalaria medicines and eating fava beans. You should also take precautions to avoid infections.

 

Recommended physical activity

Discuss with your doctor the safest types and amounts of physical activity for you. You may need to avoid certain sports or activities that could worsen your condition or lead to complications.

 

Protection from infection

Your doctor also may discuss ways to reduce your chance of getting an infection. These include staying away from people who are ill and avoiding crowds. Washing your hands thoroughly several times a day and caring for your teeth and gums can reduce the risk of infection.

 

For parents of children with hemolytic anemia

Parents of children with hemolytic anemia usually want to learn as much as possible about the illness from the team treating their child. You can be an active partner in caring for your child by speaking with the health care provider team about treatment, diet, and level of physical activity. Learn to watch for signs of worsening anemia or possible complications so you can contact your child's doctor.

 

It's a good idea for parents to educate their family members, friends, and child's classmates about the illness. You also can inform your child's teachers or other caregivers so they know about any necessary limitations or restrictions. Family members, friends, teachers, and caregivers can provide a network of support to help your child cope with his or her anemia.

 

Allow teenagers to have input in decisions about their care. This encourages them to take an active role in their health care. Help them understand about lifestyle restrictions and their medical needs so they can better cope with having anemia.