Autoimmune hemolytic anemia
Autoimmune hemolytic anemia | |
---|---|
Other names | Autoimmune haemolytic anaemia |
Specialty | Hematology |
Autoimmune hemolytic anemia (AIHA) occurs when
The terminology used in this disease is somewhat ambiguous. Although MeSH uses the term "autoimmune hemolytic anemia",[6] some sources prefer the term "immunohemolytic anemia" so drug reactions can be included in this category.[7][8] The National Cancer Institute considers "immunohemolytic anemia", "autoimmune hemolytic anemia", and "immune complex hemolytic anemia" to all be synonyms.[9]
Signs and symptoms
Symptoms of AIHA may be due to the underlying anemia; including shortness of breath or
Causes
The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness is
Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g.,
Drug-induced AIHA, though rare, can be caused by a number of drugs, including α-methyldopa and penicillin. This is a type II immune response in which the drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g., neutrophils), while other components of the system (C6, C7, C8, C9) either can form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by macrophages (C3b). This is one type of "penicillin allergy".[citation needed]
In about half of cases, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic or primary). This condition can also be caused by or occur with another disorder (secondary) or rarely, occur following the use of certain drugs (such as
Secondary causes of autoimmune hemolytic anemia include:[14]
- Autoimmune diseases, such as lupus
- Chronic lymphocytic leukemia
- blood cancers
- Epstein-Barr virus
- Cytomegalovirus
- Mycoplasma pneumonia
- Hepatitis
- HIV[14]
Pathophysiology
AIHA can be caused by a number of different classes of antibody, with
AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the Coombs test, also known as the antiglobulin test, is performed. There are two types of Coombs tests, direct and indirect; more commonly, the direct antiglobulin test (DAT) is used. Classification of the antibodies is based on their activity at different temperatures and their etiology. Antibodies with high activity at physiological temperature (approximately 37 °C) are termed warm autoantibodies. Cold autoantibodies act best at temperatures of 0–4 °C. Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state. Usually, the antibody becomes active when it reaches the limbs, at which point it opsonizes RBCs. When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of autoantibodies; if both are present, the disease is termed "mixed-type" AIHA.[citation needed]
When DAT is performed, the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with
Diagnosis
Diagnosis is made by first ruling out other causes of hemolytic anemia, such as
Laboratory investigations are carried out to determine the etiology of the disease. Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a
A
Classification
AIHA can be classified as
- Autoimmune hemolytic anemia
Evidence for hemolysis
The following findings may be present:[20][21][full citation needed]
- Increased red cell breakdown
- Elevated serum bilirubin (unconjugated)
- Excess urinary urobilinogen
- Reduced plasma haptoglobin
- Raised serum lactic dehydrogenase(LDH)
- Hemosiderinuria
- Methemalbuminemia
- Spherocytosis
- Increased red cell production:
- Reticulocytosis
- Erythroid hyperplasia of the bone marrow
- Specific investigations
- Positive direct Coombs test
Treatment
Steroids are the first line treatment in warm AIHA; with oral prednisone achieving an 80% initial response rate, with a 30-40% sustained remission rate at 1 year.
Steroids are not indicated in the treatment of cold agglutinin disease due to low response rates.[4] Cases of cold agglutinin disease with mild anemia with limited and compensated hemolysis can be monitored with adjunct supportive care (such as avoidance of cold exposure or thermal protection to prevent against hemolysis).[4] Rituximab is used to treat pathogenic B-cell clones in cold agglutinin disease with response rates of 45-60%.[4] Relapses are common upon discontinuation of rituximab, but the medication can be restarted to achieve subsequent remission.[4] Rituximab can be combined with bendamustine to achieve a 71% overall and 40% complete response rate with an increased response seen with prolonged therapy (with a time to best response at a median of 30 months) due to the drugs' effect on long lived plasma cells.[4] Splenectomy is less efficacious in cold agglutinin disease.[22]
Special considerations are required when treating people with AIHA using blood transfusion. In cold agglutinin disease; the patient and the extremity should be kept warm during transfusion to prevent agglutination and hemolysis of the donor and patient red blood cells.[4] In warm AIHA; cross-matching of blood will show incompatibility so it is recommended to perform a bedside in vivo compatibility test prior to infusion.[4] Erythropoietin (EPO) has been shown to increase hemoglobin levels in cold and warm AIHA.[4]
History
"Blood-induced icterus" produced by the release of massive amounts of a coloring material from blood cells followed by the formation of bile was recognized and described by Vanlair and Voltaire Masius' in 1871. About 20 years later, Hayem distinguished between congenital hemolytic anemia and an acquired type of infectious icterus associated with chronic splenomegaly. In 1904, Donath and Landsteiner suggested a serum factor was responsible for hemolysis in paroxysmal cold hemoglobinuria. French investigators led by Chauffard stressed the importance of red-cell
During the past three decades, studies defining red-cell blood groups and serum antibodies have produced diagnostic methods that have laid the basis for immunologic concepts relevant to many of the acquired hemolytic states. Of these developments, the antiglobulin test described by Coombs, Mourant, and Race in 1945 has proved to be one of the more important, useful tools now available for the detection of immune hemolytic states. This technique demonstrated that a rabbit antibody against human globulin would induce agglutination of human red cells "coated with an incomplete variety of rhesus antibodies". C. Moreschlit had used the same method in 1908 in a goat antirabbit-red-cell system. The test was premature and was forgotten. In 1946, Boorman, Dodd, and Loutit applied the direct antiglobulin test to a variety of hemolytic anemias, and laid the foundation for the clear distinction of autoimmune from congenital hemolytic anemia.[citation needed]
A hemolytic state exists whenever the red cell survival time is shortened from the normal average of 120 days. Hemolytic anemia is the hemolytic state in which anemia is present, and bone marrow function is inferentially unable to compensate for the shortened lifespan of the red cell. Immune hemolytic states are those, both anemic and nonanemic, which involve immune mechanisms consisting of antigen-antibody reactions. These reactions may result from unrelated antigen-antibody complexes that fix to an innocent-bystander erythrocyte, or from related antigen-antibody combinations in which the host red cell or some part of its structure is or has become antigenic. The latter type of antigen-antibody reaction may be termed "autoimmune", and hemolytic anemias so produced are autoimmune hemolytic anemias.[2]
In children
In general, AIHA in children has a good prognosis and is self-limiting. However, if it presents within the first two years of life or in the teenage years, the disease often follows a more
See also
- Hematology
- Hemolytic anemia
- List of circulatory system conditions
- List of hematologic conditions
- Splenomegaly
References
- ^ Shoenfield, Y; et al. (2008). Diagnostic Criteria in Autoimmune Disease. Humana Press.
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- ^ Autoimmune+hemolytic+anemia at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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- ^ "Definition of immunohemolytic anemia". NCI Dictionary of Cancer Terms. Archived from the original on 15 January 2009. Retrieved 2009-02-07.
- ^ "Autoimmune hemolytic anemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov.
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- ^ a b c "Autoimmune hemolytic anemia". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2014-02-24. Retrieved 2019-05-28. This article incorporates text from this source, which is in the public domain.
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- ^ Kumar P, Clark M (2005). Clinical Medicine (6th ed.). Elsevier Saunders. p. 437.
- ^ "Autoimmune Hemolytic Anemia". The Lecturio Medical Concept Library. Retrieved 3 July 2021.
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