Warm autoimmune hemolytic anemia
Encyclopedia
Warm Antibody Autoimmune Hemolytic Anemia (AIHA) is the most common of the autoimmune hemolytic
diseases. About half of the cases are idiopathic
, with the other half attributable to a predisposing condition or medications being taken.
involved in warm antibody AIHA is IgG, though sometimes IgA
is found. The IgG antibodies attach to a red blood cell, leaving their FC portion exposed. The FC region is recognized and grabbed onto by FC receptors found on monocytes and macrophages in the spleen
. These cells will pick off portions of the red cell membrane, almost like they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes. Spherocytes are not as flexible as normal RBCs, and will be singled-out for destruction in the red pulp of the spleen as well as other portions of the reticuloendothelial system. The red blood cells trapped in the spleen cause the spleen to enlarge, leading to the splenomegaly
often seen in these patients.
There are two models for this: the hapten
model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin
and cephalosporins, will bind to certain proteins on the red cell membrane and act as haptens. Antibodies are created against the protein-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence.
It is possible for it to occur in an immunocompromised patient.
, increased mean corpuscular volume (MCV, due to the presence of a large number of young erythrocytes), and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.
, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.
should be considered.
If refractory to both these therapies, other options include rituximab
, danazol
, cyclosphosphamide, azathioprine
, or cyclosporine.
High dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1–4 weeks), and the therapy is very expensive.
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
diseases. About half of the cases are idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
, with the other half attributable to a predisposing condition or medications being taken.
Pathophysiology
The most common antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
involved in warm antibody AIHA is IgG, though sometimes IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
is found. The IgG antibodies attach to a red blood cell, leaving their FC portion exposed. The FC region is recognized and grabbed onto by FC receptors found on monocytes and macrophages in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
. These cells will pick off portions of the red cell membrane, almost like they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes. Spherocytes are not as flexible as normal RBCs, and will be singled-out for destruction in the red pulp of the spleen as well as other portions of the reticuloendothelial system. The red blood cells trapped in the spleen cause the spleen to enlarge, leading to the splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
often seen in these patients.
There are two models for this: the hapten
Hapten
A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself...
model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
and cephalosporins, will bind to certain proteins on the red cell membrane and act as haptens. Antibodies are created against the protein-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence.
It is possible for it to occur in an immunocompromised patient.
Causes
AIHA may be:- Idiopathic, that is, without any known cause
- Secondary to another disease, such as systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
or rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
or a malignancy, such as chronic lymphocytic leukemiaChronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
(CLL) - Associated with receiving a drug
Clinical findings
Laboratory findings include severe anemiaAnemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, increased mean corpuscular volume (MCV, due to the presence of a large number of young erythrocytes), and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.
Diagnosis
Diagnosis is made by a positive direct Coombs testCoombs test
Coombs test refers to two clinical blood tests used in immunohematology and immunology...
, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.
Treatment
Corticosteroids and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial medical treatment consists of prednisone. If ineffective, splenectomySplenectomy
A splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
should be considered.
If refractory to both these therapies, other options include rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, danazol
Danazol
Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. It was approved by the U.S. Food and Drug Administration as the...
, cyclosphosphamide, azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, or cyclosporine.
High dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1–4 weeks), and the therapy is very expensive.
External links
- Case report of warm-antibody autoimmune hemolytic anemia with typical laboratory findings. Clinical Cases and Images.