Warm Antibody Autoimmune Hemolytic Anemia (AIHA) is the most common of the autoimmune
hemolyticHemolysis —from the Greek Hemo-, Greek meaning blood, -lysis, meaning to break open—is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
diseases. About half of the cases are
idiopathicIdiopathic 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."...
, with the other half attributable to a predisposing condition or medications being taken.
The most common
antibodyAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
involved in warm antibody AIHA is IgG, though sometimes
IgAIga or IGA may stand for:-Places :* Iga, a city in Mie Prefecture, Honshū island, Japan** Iga Ueno Castle, a castle located in the above city...
is found. The IgG antibodies attach to a red blood cell, leaving their F
C portion exposed.
Warm Antibody Autoimmune Hemolytic Anemia (AIHA) is the most common of the autoimmune
hemolyticHemolysis —from the Greek Hemo-, Greek meaning blood, -lysis, meaning to break open—is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
diseases. About half of the cases are
idiopathicIdiopathic 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."...
, with the other half attributable to a predisposing condition or medications being taken.
Pathophysiology
The most common
antibodyAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
involved in warm antibody AIHA is IgG, though sometimes
IgAIga or IGA may stand for:-Places :* Iga, a city in Mie Prefecture, Honshū island, Japan** Iga Ueno Castle, a castle located in the above city...
is found. The IgG antibodies attach to a red blood cell, leaving their F
C portion exposed. The F
C region is recognized and grabbed onto by F
C receptors found on monocytes and macrophages in the
spleenThe 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, holds a reserve in case of hemorrhagic shock, especially in...
. 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.
The cause of the autoantibody formation is unknown, but the mechanism for drug-induced destruction is better understood. There are two models for this: the
haptenA 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
penicillinPenicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections...
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.
Clinical findings
Laboratory findings include severe
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
, 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 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,
splenectomyA splenectomy is a procedure that involves the removal of the spleen by operative means.-Indications:Indications of splenectomy can be divided into general and specific indications. For general indications, they include the following:-Procedure:...
should be considered.
If refractory to both these therapies, other options include
rituximabRituximab, 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...
,
danazolDanazol 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,
azathioprineAzathioprine is a drug that suppresses the immune system.Azathioprine is used in organ transplantation and autoimmune disease. Some of the autoimmune diseases are rheumatoid arthritis, pemphigus, Inflammatory Bowel Disease , multiple sclerosis, autoimmune hepatitis and restrictive lung...
, 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.
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