Hemolysis is the premature destruction of erythrocytes.

A hemolytic anemia will develop if bone marrow activity cannot compensate for the erythrocyte loss. The severity of the anemia depends on whether the onset of hemolysis is gradual or abrupt and on the extent of erythrocyte destruction. Mild hemolysis can be asymptomatic while the anemia in severe hemolysis can be life threatening and cause angina and cardiopulmonary decompensation. The clinical presentation also reflects the underlying cause for hemolysis. For example, sickle cell anemia (see the image below) is associated with painful occlusive crises. (See Clinical.)

Peripheral blood smear with sickled cells at 1000X magnification. Image courtesy of Ulrich Woermann, MD. There are multiple causes for hemolytic anemia, and the clinical presentation can differ depending on the etiology. An array of laboratory tests are available for detecting hemolysis, and specialized tests may be indicated to diagnose the cause for hemolysis (see Workup). There are differences in the management of various types of hemolytic anemias (see Treatment).

Pathophysiology
Hemolysis can be due to hereditary and acquired disorders. The etiology of premature erythrocyte destruction is diverse and can be due to conditions such as intrinsic membrane defects, abnormal hemoglobins, erythrocyte enzymatic defects, immune destruction of erythrocytes, mechanical injury, and hypersplenism. Hemolysis may be an extravascular or an intravascular phenomenon. Autoimmune hemolytic anemia and hereditary spherocytosis are examples of extravascular hemolysis because the red blood cells are destroyed in the spleen and other reticuloendothelial tissues.[1] Intravascular hemolysis occurs in hemolytic anemia due to prosthetic cardiac valves, G-6-PD deficiency, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, following transfusion of ABO incompatible blood, and paroxysmal nocturnal hemoglobinuria (PNH). Hemolysis may also be intramedullary when fragile RBC precursors are destroyed in the bone marrow prior to release into the circulation. Intramedullary hemolysis occurs in pernicious anemia and thalassemia major.

Hemolysis is associated with a release of RBC lactate dehydrogenase (LDH). Hemoglobin released from damaged RBC leads to an increase in indirect bilirubin and urobilinogen. A patient with mild hemolysis may have normal hemoglobin levels if increased RBC production matches the rate of RBC destruction. However, patients with mild hemolysis may develop marked anemia if their bone marrow erythrocyte production is transiently shut off by viral (parvovirus B-19) or other infections. This scenario would be an aplastic crisis since the bone marrow can no longer compensate for ongoing hemolysis. Skull and skeletal deformities can occur in childhood due to a marked increase in hematopoiesis and resultant bone marrow expansion in disorders such as thalassemia The various types of hemolytic anemia have been documented.[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14] Only the more commonly encountered hemolytic disorders are discussed in this article. Hereditary disorders include erythrocyte membrane, enzymatic defects, and hemoglobin abnormalities. Hereditary disorders include the following:

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency Hereditary spherocytosis Sickle cell anemia

Acquired causes of hemolysis include immune disorders, toxic chemicals and drugs,[3, 8, 15] antiviral agents (eg, ribavirin[16] ) physical damage, and infections.[17] Autoimmune hemolytic anemia (AIHA) can be due to warm or cold autoantibody types; and rarely, mixed types.[18, 19, 20] Most warm autoantibodies belong to the immunoglobulin IgG class. These antibodies can be detected by a direct Coombs test, which also is known as a direct antiglobulin test (DAT). AIHA may occur after allogeneic hematopoietic stem cell transplantation. The 3-year cumulative incidence in this population has been reported at 4.44%.[21] Microangiopathic hemolytic anemia is found in patients with defective prosthetic cardiac valves, disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP).[22, 23] Fragmented erythrocytes (schistocytes) are seen in microangiopathic hemolytic anemias.[4] In PNH, hemolysis is due to intravascular complement-mediated destruction of erythrocytes.

Prognosis
The prognosis for patients with hemolytic anemia depends on the underlying cause.

Overall, mortality rates are low in hemolytic anemias. However, the risk is greater in older patients and patients with cardiovascular impairment. Morbidity depends on the etiology of the hemolysis and the underlying disorder such as sickle cell anemia or malaria Autoimmune hemolytic anemia is a group of disorders characterized by a malfunction of the immune system that produces autoantibodies, which attack red blood cells as if they were substances foreign to the body.

Some people have no symptoms, and other people are tired, short of breath, and pale. Severe disease may cause jaundice or abdominal discomfort and fullness. Blood tests are used to detect anemia and determine the cause of the autoimmune reaction. Some people need corticosteroids or drugs that suppress the immune system.

Autoimmune hemolytic anemia is an uncommon group of disorders that can occur at any age. These disorders affect women more often than men. About half of the time, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic autoimmune hemolytic anemia). Autoimmune hemolytic anemia can also be caused by or occur with another disorder, such as systemic lupus erythematosus (lupus), and rarely it follows the use of certain drugs, such as penicillin. Destruction of red blood cells by autoantibodies may occur suddenly, or it may develop gradually. In some people, the destruction may stop after a period of time. In other people, red blood cell destruction persists and becomes chronic. There are two main types of autoimmune hemolytic anemia: warm antibody hemolytic anemia and cold antibody hemolytic anemia. In the warm antibody type, the autoantibodies attach to and destroy red blood cells at temperatures equal to or in excess of normal body temperature. In the cold antibody type, the autoantibodies become most active and attack red blood cells only at temperatures well below normal body temperature. Symptoms Some people with autoimmune hemolytic anemia may have no symptoms, especially when the destruction of red blood cells is mild and develops gradually. Others have symptoms similar to those that occur with other types of anemia, especially when the destruction is more severe or rapid. When severe or rapid destruction of red blood cells occurs, mild jaundice may also develop. When destruction persists for a few months or longer, the spleen may enlarge, resulting in a sense of abdominal fullness and, occasionally, discomfort. When the cause of autoimmune hemolytic anemia is another disease, symptoms of the underlying disorder, such as swollen and tender lymph nodes and fever, may dominate.

Diagnosis Once doctors diagnose anemia, increased destruction of red blood cells is suspected when a blood test shows an increase in the number of red blood cells that are immature (reticulocytes). Alternatively, a blood test may show an increased amount of a substance called bilirubin and a decreased amount of a protein called haptoglobin. Autoimmune hemolytic anemia as the cause is confirmed when blood tests detect increased amounts of certain antibodies, either attached to red blood cells (direct antiglobulin or direct Coombs' test) or in the liquid portion of the blood (indirect antiglobulin or indirect Coombs' test). Other tests sometimes help determine the cause of the autoimmune reaction that is destroying red blood cells. Treatment If symptoms are mild or if destruction of red blood cells seems to be slowing on its own, no treatment is needed. If red blood cell destruction is increasing, a corticosteroid such as prednisone is usually the first choice for treatment. High doses are used at first, followed by a gradual reduction of the dose over many weeks or months. When people do not respond to corticosteroids or when the corticosteroid causes intolerable side effects, surgery to remove the spleen (splenectomy) is often the next treatment. The spleen is removed because it is one of the places where antibody-coated red blood cells are destroyed. When destruction of red blood cells persists after removal of the spleen or when surgery cannot be done, immunosuppressive drugs, such as cyclophosphamideSome Trade Names LYOPHILIZED CYTOXAN or azathioprineSome Trade Names IMURAN , are used. When red blood cell destruction is severe, blood transfusions are sometimes needed, but they do not treat the cause of the anemia and provide only temporary relief.