Autoimmune hemolytic anemia
Encyclopedia
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells
(RBCs) cause the RBCs to burst (lyse), leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens
, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion) AIHA is a relatively rare condition affecting 1–3 people per 100,000 per year .
The terminology used in this disease is somewhat ambiguous. Although MeSH
uses the term "autoimmune hemolytic anemia", some sources prefer the term "immunohemolytic anemia" so that drug reactions can be included in this category.. The National Cancer Institute
considers "immunohemolytic anemia", "autoimmune hemolytic anemia", and "immune complex hemolytic anemia" to all be synonyms..
or cold autoimmune hemolytic anemia which includes cold agglutinin disease, and paroxysmal cold hemoglobinuria
. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each of these has a different underlying cause, management and prognosis making classification important when handling a patient with AIHA.
(the two terms being used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. 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. chronic lymphocytic leukemia
, lymphoma
) and other autoimmune disorders (e.g. systemic lupus erythematosis, rheumatoid arthritis
, scleroderma
, ulcerative colitis
). Less common causes of warm-type AIHA include neoplasms other than lymphoid and infection. Secondary cold type AIHA is also primarily caused by lymphoproliferative disorders but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis and other respiratory infections. Less commonly it can be caused by concomitant autoimmune disorders.
Drug induced AIHA is also a rare cause of the disease. It 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 RBC and acts as an antigen. Antibodies are produced against the RBC and lead 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) can either form the membrane attack complex (MAC) or can bind the antibody stimulating phagocytosis by macrophages
(C3b). This is one type of "penicillin allergy".
. IgG and IgM
are the main classes of antibody which cause the disease. Depending on which is involved the pathology
will differ. As IgG is poor at activating complement
but effectively binds the Fc receptor
(FcR) of phagocytic cells, AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the classical complement pathway
, thus, AIHA involving IgM is characterized by complement mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). IgG AIHA generally takes place in the spleen
, while IgM AIHA takes place in Kupffer cells – phagocytic cells of the liver
. Phagocytic AIHA is termed extravascular while complement mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG or IgM mediated.
There is no single autoantibody which can be pinned down in AIHA. In order to determine the autoantibody or autoantibodies present in a patient, the Coombs test
is performed – also known as the antiglobulin test. There are two types of Coombs test – direct and indirect – more commonly the direct test is used (direct antiglobulin test – DAT). Classification of the antibodies is based on their activity at different temperatures and their aetiology. 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 autoantibody, if both are present the disease is termed "mixed-type" AIHA.
When DAT is performed the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with antisera
to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with IgA
, IgM or a combination of these three antibody classes and complement. Cold type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. Mixed warm and cold AIHA generally shows a positive reaction to IgG and complement, sometimes IgG alone and sometimes complement alone. Mixed type can, like the others, present unusually with positive reactions to other antisera.
, thalassemia
, sickle-cell disease
, etc. Clinical history is also important to elucidate any underlying illness or medications which may have led to the disease.
Following this, laboratory investigations are carried out to determine the etiology of the disease. A positive DAT test has poor specificity for AIHA (having many differential diagnoses), therefore supplemental serological testing is required to ascertain the cause of the positive reaction. Hemolysis must also be demonstrated in the lab. The typical tests used for this are a CBC with peripheral smear, bilirubin, LDH (in particular with isoenzyme 1), haptoglobin and urine hemoglobin.
Evidence for hemolysis
Specific investigations
Warm type AIHA is usually a more insidious disease, not treatable by simply removing the underlying cause. First line therapy for this is usually with corticosteroids
such as prednisolone
. Following this, other immunosuppressants are considered such as rituximab
, danazol
, cyclophosphamide
, azathioprine
or cyclosporine.
Cold agglutinin disease is treated by avoiding the cold or sometimes with rituximab. Removal of the underlying cause is also important
Paroxysmal cold hematuria is treated by removing the underlying cause such as infection.
in patients with acquired hemolytic anemia. In 1930 Lederer and Brill described cases of acute hemolysis
with rapid onset of anemia and rapid recovery after transfusion therapy. These hemolytic episodes were thought to be due to infectious agents. A clear distinction between congenital and acquired hemolytic anemia was not drawn, however, until Dameshek and Schwartz in 1938 and in 1940 demonstrated the presence of abnormal hemolysins in the sera of patients with acquired hemolytic anemia
and postulated an immune mechanism
.
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 importantly 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 antibody." C. Moreschlit had used the same method in 1908 in a goat antirabbit-red-cell system. The test was historically 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.
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 life-span of the red cell. Immune hemolytic states are those hemolytic states, 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.
with serious developmental consequences. The aim of therapy may sometimes be to lower the use of steroids in the control of the disease. In this case, splenectomy
may be considered as well as other immunosuppressive drugs. Infection is a serious concern in patients on long-term immunosuppressant therapy, especially in the very young (<2 years).
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
(RBCs) cause the RBCs to burst (lyse), leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion) AIHA is a relatively rare condition affecting 1–3 people per 100,000 per year .
The terminology used in this disease is somewhat ambiguous. Although MeSH
Medical Subject Headings
Medical Subject Headings is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it can also serve as a thesaurus that facilitates searching...
uses the term "autoimmune hemolytic anemia", some sources prefer the term "immunohemolytic anemia" so that drug reactions can be included in this category.. The National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
considers "immunohemolytic anemia", "autoimmune hemolytic anemia", and "immune complex hemolytic anemia" to all be synonyms..
Classification
AIHA is classified as either warm autoimmune hemolytic anemiaWarm autoimmune hemolytic anemia
Warm Antibody Autoimmune Hemolytic Anemia 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.-Pathophysiology:...
or cold autoimmune hemolytic anemia which includes cold agglutinin disease, and paroxysmal cold hemoglobinuria
Paroxysmal cold hemoglobinuria
Paroxysmal cold hemoglobinuria is a disease of humans that is characterized by the sudden presence of hemoglobin in the urine , typically after exposure to cold temperatures....
. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each of these has a different underlying cause, management and prognosis making classification important when handling a patient with AIHA.
Causes
The causes of AIHA are poorly understood. The disease may be primary or secondary to another underlying illness. The primary illness is idiopathicIdiopathic
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...
(the two terms being used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. 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. chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-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...
, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
) and other autoimmune disorders (e.g. systemic lupus erythematosis, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid 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...
, scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
). Less common causes of warm-type AIHA include neoplasms other than lymphoid and infection. Secondary cold type AIHA is also primarily caused by lymphoproliferative disorders but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis and other respiratory infections. Less commonly it can be caused by concomitant autoimmune disorders.
Drug induced AIHA is also a rare cause of the disease. It can be caused by a number of drugs including α-methyldopa
Methyldopa
Methyldopa is an alpha-adrenergic agonist psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents...
and penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
. This is a type II immune response
Type II hypersensitivity
In type II hypersensitivity the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces...
in which the drug binds to macromolecules
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
on the surface of the RBC and acts as an antigen. Antibodies are produced against the RBC and lead 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) can either form the membrane attack complex (MAC) or can bind the antibody stimulating phagocytosis by macrophages
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
(C3b). This is one type of "penicillin allergy".
Pathophysiology
AIHA can be caused by a number of different autoantibodiesAutoantibody
An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...
. IgG and IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
are the main classes of antibody which cause the disease. Depending on which is involved the pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
will differ. As IgG is poor at activating complement
Complement
In many different fields, the complement of X is something that together with X makes a complete whole—something that supplies what X lacks.Complement may refer to:...
but effectively binds the Fc receptor
Fc receptor
An Fc receptor is a protein found on the surface of certain cells - including natural killer cells, macrophages, neutrophils, and mast cells - that contribute to the protective functions of the immune system....
(FcR) of phagocytic cells, AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the classical complement pathway
Classical complement pathway
The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...
, thus, AIHA involving IgM is characterized by complement mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). IgG AIHA generally takes place 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...
, while IgM AIHA takes place in Kupffer cells – phagocytic cells of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Phagocytic AIHA is termed extravascular while complement mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG or IgM mediated.
There is no single autoantibody which can be pinned down in AIHA. In order to determine the autoantibody or autoantibodies present in a patient, the Coombs test
Coombs test
Coombs test refers to two clinical blood tests used in immunohematology and immunology...
is performed – also known as the antiglobulin test. There are two types of Coombs test – direct and indirect – more commonly the direct test is used (direct antiglobulin test – DAT). Classification of the antibodies is based on their activity at different temperatures and their aetiology. 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 autoantibody, if both are present the disease is termed "mixed-type" AIHA.
When DAT is performed the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with antisera
Antiserum
Antiserum is blood serum containing polyclonal antibodies. Antiserum is used to pass on passive immunity to many diseases. Passive antibody transfusion from a previous human survivor is the only known effective treatment for Ebola infection .The most common use of antiserum in humans is as...
to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with 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....
, IgM or a combination of these three antibody classes and complement. Cold type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. Mixed warm and cold AIHA generally shows a positive reaction to IgG and complement, sometimes IgG alone and sometimes complement alone. Mixed type can, like the others, present unusually with positive reactions to other antisera.
Diagnosis
Diagnosis is made by first ruling out other causes of hemolytic anemia such as G6PDGlucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
, thalassemia
Thalassemia
Thalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
, sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
, etc. Clinical history is also important to elucidate any underlying illness or medications which may have led to the disease.
Following this, laboratory investigations are carried out to determine the etiology of the disease. A positive DAT test has poor specificity for AIHA (having many differential diagnoses), therefore supplemental serological testing is required to ascertain the cause of the positive reaction. Hemolysis must also be demonstrated in the lab. The typical tests used for this are a CBC with peripheral smear, bilirubin, LDH (in particular with isoenzyme 1), haptoglobin and urine hemoglobin.
Evidence for hemolysis
- Increased red cell breakdown
- Elevated serum bilirubinBilirubinBilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
(unconjugated) - Excess urinary urobilinogenUrobilinogenUrobilinogen is a colourless product of bilirubin reduction. It is formed in the intestines by bacterial action. Some urobilinogen is reabsorbed, taken up into the circulation and excreted by the kidney. This constitutes the normal "enterohepatic urobilinogen cycle".Increased amounts of bilirubin...
- Reduced plasma haptoglobinHaptoglobinHaptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...
- Raised serum lactic dehydrogenase (LDH)
- HemosiderinuriaHemosiderinuriaHemosiderinuria , "brown urine", occurs with chronic intravascular hemolysis, in which hemoglobin is released from RBCs into the bloodstream in excess of the binding capacity of haptoglobin. The excess hemoglobin is filtered by the kidney and reabsorbed in the proximal tubule, where the iron...
- methemalbuminemia
- Elevated serum bilirubin
- Increased red cell production:
- ReticulocytosisReticulocytosisReticulocytosis is a condition where there is an increase in reticulocytes, immature red blood cell.It is commonly seen in Anemia. They are seen on blood films when the bone marrow is highly active in an attempt to replace red blood cell loss such as in haemolytic anaemia, haemorrhage.-External...
- Erythroid hyperplasia of the bone marrow
- Reticulocytosis
Specific investigations
- Positive direct Coombs testCoombs testCoombs test refers to two clinical blood tests used in immunohematology and immunology...
Treatment
Much literature exists regarding the treatment of AIHA. Efficacy of treatment depends on the correct diagnosis of either warm or cold-type AIHA.Warm type AIHA is usually a more insidious disease, not treatable by simply removing the underlying cause. First line therapy for this is usually with corticosteroids
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
such as prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
. Following this, other immunosuppressants are considered such as 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...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, 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.
Cold agglutinin disease is treated by avoiding the cold or sometimes with rituximab. Removal of the underlying cause is also important
Paroxysmal cold hematuria is treated by removing the underlying cause such as infection.
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 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 that a serum factor was responsible for hemolysis in paroxysmal cold hemoglobinuria. French investigators led by Chauffard stressed the importance of red-cell autoagglutinationAutoagglutination
Autoagglutination represents clumping of an individual's red blood cells by his or her own serum due to the RBCs being coated on their surface by antibodies....
in patients with acquired hemolytic anemia. In 1930 Lederer and Brill described cases of acute hemolysis
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...
with rapid onset of anemia and rapid recovery after transfusion therapy. These hemolytic episodes were thought to be due to infectious agents. A clear distinction between congenital and acquired hemolytic anemia was not drawn, however, until Dameshek and Schwartz in 1938 and in 1940 demonstrated the presence of abnormal hemolysins in the sera of patients with acquired hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
and postulated an immune mechanism
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
.
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 importantly 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 antibody." C. Moreschlit had used the same method in 1908 in a goat antirabbit-red-cell system. The test was historically 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.
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 life-span of the red cell. Immune hemolytic states are those hemolytic states, 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.
In Children
AIHA in children generally 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 chronic course, requiring long term immunosuppressionImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
with serious developmental consequences. The aim of therapy may sometimes be to lower the use of steroids in the control of the disease. In this case, splenectomy
Splenectomy
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...
may be considered as well as other immunosuppressive drugs. Infection is a serious concern in patients on long-term immunosuppressant therapy, especially in the very young (<2 years).
See also
- HematologyHematologyHematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
- Hemolytic anemiaHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
- List of circulatory system conditions
- List of hematologic conditions
External links
- Case report of Autoimmune Hemolytic Anemia with typical laboratory findings. Clinical Cases and Images.