Anemia

Hemolytic Anemias

Rarely, anemia is due to problems that cause the red blood cells (RBCs) to die or be destroyed prematurely. Normally, red cells live in the blood for about 4 months. In hemolytic anemia, this time is shortened, sometimes to only a few days. The bone marrow is not able to produce new RBCs quickly enough to replace those that have been destroyed, leading to a decreased number of RBCs in the blood, which in turn leads to a diminished capacity to supply oxygen to tissues throughout the body. This results in the typical symptoms of anemia including:

• weakness and/or fatigue
• lack of energy

Depending on the cause, different forms of hemolytic anemia can be chronic, developing and lasting over a long period or lifetime, or may be acutesigns and symptoms. The various forms can have a wide range of signs and symptoms. See the discussions of the various types below for more on this.

The different causes of hemolytic anemia fall into two main categories:

• Inherited forms in which a gene or genes are passed from one generation to the next that result in abnormal RBCs or hemoglobin
• Acquired forms in which some factor other than inherited results in the early destruction of RBCs

Inherited Hemolytic Anemia
Two of the most common causes of inherited hemolytic anemia are sickle cell anemia and thalassemia:

Sickle cell anemia can cause minor difficulties as the “trait” (when you carry one mutated gene from one of your parents), but severe clinical problems as the “disease” (when you carry two mutated genes, one from each of your parents). The red blood cells are misshapen, unstable (leading to hemolysis) and can block blood vessels, causing pain and anemia. Screening is usually done on newborns – particularly those of African descent. Sometimes screening is done prenatally on a sample of amniotic fluid. Follow-up tests for hemoglobin variants may be performed to confirm a diagnosis. Treatment is usually based on the type, frequency and severity of symptoms.

Thalassemia is a hereditary abnormality of hemoglobin production and results in small red blood cells that resemble those seen in iron deficiency. In its most severe form, the red cells have a shortened life span. In milder forms, anemia is usually mild or absent, and the disease may be detected by finding small blood cells on a routine CBC. This genetic disease is found frequently in people of Mediterranean, African, and Asian heritage. The defect in production may involve one of two components of hemoglobin called the alpha and beta protein chains. The disease is defined as alpha thalassemia or beta thalassemia accordingly. The "beta minor" form (sometimes called beta thal trait, as with sickle cell) occurs when a person inherits half normal genes and half beta thalassemia genes. It causes a mild anemia and no symptoms. The "beta major" form (due to inheriting two beta thalassemia genes and also called Cooley’s anemia) is more severe and may result in growth problems, jaundice, and severe anemia.

Other less common types of inherited forms of hemolytic anemia include:

• Hereditary spherocytosis—results in abnormally shaped RBCs that may be seen on a blood smear
• Hereditary elliptocytosis—another cause of abnormally shaped RBCs seen on a blood smear
• Glucose-6-phospate dehydrogenase (G6PD) deficiency—G6PD is an enzyme that is necessary for RBC survival. Its deficiency may be diagnosed with a test for its activity.
• Pyruvate kinase deficiency—Pyruvate kinase is another enzyme important for RBC survival and its deficiency may also be diagnosed with a test for its activity.

Laboratory Tests
Since some of these inherited forms may have mild symptoms, they may first be detected on a routine CBC and blood smear, which can reveal various abnormal results that give clues as to the cause. Follow-up tests are then usually performed to make a diagnosis. Some of these include:

• Tests for hemoglobin variants such as hemoglobin electrophoresis
• DNA analysis—not routinely done but can be used to help diagnose hemoglobin variants, thalassemia, and to determine carrier status.
• G6PD test—to detect deficiency in this enzyme
• Osmotic fragility test—detects RBCs that are more fragile than normal, which may be found in hereditary spherocytosis.

These genetic disorders cannot be cured but often the symptoms resulting from the anemia may be alleviated with treatment as necessary.

Acquired Hemolytic Anemia
Some of the conditions or factors involved in acquired forms of hemolytic anemia include:

• Autoimmune disorders—a condition in which the body produces antibodies against its own red blood cells. It is not understood why this may happen.
• Transfusion reaction—result of blood donor-recipient incompatibility. This occurs very rarely but when it does, it can have some serious complications. For more on this, see the Blood Banking article.
• Mother-baby blood group incompatibility—may result in hemolytic disease of the newborn.
• Drugs—certain drugs such as penicillin can trigger the body to produce antibodies directed against RBCs or cause the direct destruction of RBCs.
• Physical destruction of RBCs by, for example, an artificial heart valve or cardiac bypass machine used during open-heart surgery
• Paroxysmal Nocturnal Hemoglobinurina (PNH)—a rare condition in which the different types of blood cells including RBCs, WBCs and platelets are abnormal. Because the RBCs are defective, they are destroyed by the body earlier than the normal lifespan. As the name suggests, people with this disorder can have acute, recurring episodes in which many RBCs are destroyed. This disease occurs due to a change or mutation in a gene called PIGA in the stem cells that make blood. Though it is a genetic disorder, it is not passed from one generation to the next (it is not an inherited condition). Patients will often pass dark urine due to the hemoglobin released by destroyed RBCs being cleared from the body by the kidneys. This is most noticeable first thing in the morning when urine is most concentrated. Episodes are thought to be brought on when the body is under stress during illnesses or after physical exertion. For more on this, see the Genetic Home Reference webpage.

These types of hemolytic anemias are often first identified by signs and symptoms, during physical examination, and by medical history. A medical history can reveal, for example, a recent transfusion, treatment with penicillin, or cardiac surgery. A CBC and/or blood smear may show various abnormal results. Depending on those findings, additional follow-up tests may be performed. Some of these may include:

• Tests for autoantibodies for suspected autoimmune disorders
• Direct antiglobulin test (DAT) in the case of transfusion reaction, mother-baby blood type incompatibility, or autoimmune hemolytic anemia
• Haptoglobin
• Reticulocyte count

Treatments for hemolytic anemia are as varied as the causes. However, the goals are the same: to treat the underlying cause of the anemia, to decrease or stop the destruction of RBCs, and to increase the RBC count and/or hemoglobin level to alleviate symptoms. This may involve, for example:

• Drugs used to decrease production of autoantibodies that destroy RBCs
• Blood transfusions to increase the number of healthy RBCs
• Bone marrow transplant—to increase production of normal RBCs
• Avoiding triggers that cause the anemia such as the cold in some forms of autoimmune hemolytic anemia or fava beans for those with G6PD deficiency.