Friday, March 29, 2019
The Autoimmune Hemolytic Anemia Biology Essay
The autoresistant Hemolytic Anemia Biology EssayAutoimmunity is a affection in which an organism loses its ability to recognize the self and non-self antigen, which would further lead to immune repartee against its avouch booths and tissues. Diseases that results from such abnormal immune responses be termed as autoimmune diseases. autoimmune haemolytic genus Anemia (AIHA) is an autoimmune disorder in which endogenous antibodies be directed against the bolshy pipeline cells and upregulated leading to bolshy blood cell death. This review article focuses on the types of AIHA base on the classification of the antibodies and the temperature at which they argon characterizationive i.e fond(p) AIHA, chilly AIHA and mixed AIHA , based on the age of its occurance i.e adult or paediatric AIHA, bears, diagnostic techniques, diseases which whitethorn cause AIHA as a supplemental disorder, treatment and its later oneffects, current and future prospectives of its studies.Abb reviations AIHA Autoimmune haemolytic anemia, WAIHA sore autoimmune hemolytic anemia, CAIHA refrigerating autoimmune hemolytic anemia, red blood cells Red blood cells, DAT Direct antiglobin ravel.INTRODUCTIONAutoimmune hemolytic anemia (AIHA) is a disorder in which the auto-antibodies are directed against the persons own red blood cells (1). It is a relatively uncommon but non a grand disorder. It has an estimated incidence of 1 to 3 shells per 100,000 population per year (1). There are three types of AIHA based on the temperature of natural process of the autoantibodies i.e warm AIHA, ice-cold AIHA and mixed type AIHA of which warm AIHA has the most common occurance ( to a greater extent(prenominal)(prenominal) than 70%) followed by cold AIHA (about 20%) and mixed type has least occurance (2). and AIHA is classified ad on the basis of age of the patient suffering from the disorder i.e pediatric AIHA and adult AIHA. Pediatric AIHA is from the age group of 1 to 16 (o r 18) broad time and mostly has no vestigial causes (2). Adult AIHA is from 18 years and to a higher place and is mostly associated with both(prenominal) underlying primal diseases. Sometimes AIHA is cause c every last(predicate)able to administration of some doses and is called drug induced AIHA. AIHA whitethorn also be of secondary or idiopathic type. The further description of the different types of AIHA is explained below.TYPES OF AIHA base on the temperature at which the auto-antibodies are activeWarm autoimmune hemolytic anemia (WAIHA)It the most common type of AIHA. Warm auto-antibodies are normally IgG. It is called warm autoimmune hemolytic anemia because the antibodies have their peak employment at 370C. IgG effectively binds to the FC receptor of phagocytic cells. Hence the ravaging of erythrocytes takes place mostly by phagocytosis. IgG may or may not fix complement. Hemolysis of RBCs also takes place in spleen. WAIHA may be idiopathic i.e when there is no unc reated infection causation the disorder or secondary to lymphoproliferative diseases, autoimmune diseases, viral infections, immune want etc (1)(2)(3)(6).Cold autoimmune hemolytic anemia (CAIHA)Cold auto-antibodies are ordinarily IgM antibodies. Rarely IgG or IgA antibodies can act as cold auto-antibodies. It is so called because the antibodies have their peak activity at temperature ranging from 0-40 C (1)(2)(3)(6). IgM antibodies are potent classical complement roadway activators. Hence causes complement mediated lysis of RBCs.Paraxysmal cold hemoglobinurea a form of CAIHA, is ca utilise by cold active IgG hemolysin. It was unremarkably associated with some underlying diseases homogeneous syphilis, measles, mumps or other viral diseases (1)(2)(6).Mixed autoimmune hemolytic anemiaBoth warm auto-antibodies and cold auto-antibodies are indue the blood. It is more fatal than the WAIHA and CAIHA. Detection and diagnosis is also more difficult than the introductory types (1)(2) (3)(4)(6).Based on the age of the patient suffering from the disorder AIHA is classified asPediatric AIHAAffects the age group of 1-16 years, with a high incidence of occurance in the first four years of life (1). It may ad libitum resolve on its own. It shows a good response to the steroid treatment. It has a sinful onset and less morbity rate. Males are more prone to pediatric AIHA (2).Adult AIHAAffects the age group of 18 years and above. It is more much associated with the underlying lymphoproliferative, autoimmune and infectious diseases. Treatment is steroid therapy or spleenectomy. Has higher morbity rate compared to adult AIHA because of the difficulty or inability in treating the underlying disease (2).Based on the cause of its occurance, quest are the types of AIHA substitute AIHAIt is chiefly caused ascribable to some underlying diseases same bacterial, fungal or viral infections. The primary underlying diseases that may cause secondary AIHA are Sjogrens syndrome ( 10), lymphoproliferative and autoimmune diseases (2).Treatment of the secondary AIHA would also include the treatment of the underlying primary disease, for its complete remission (1).Idiopathic AIHAHas no particular underlying causes like infections or primary diseases for its occurance. Mortality rate is comparatively less than that of secondary AIHA (1).Drug induced AIHACause of occurance are drug molecules that binds to the surface of the RBC membrane, acts as non-self antigens, thus inducing the autoantibodies against the RBCs and further leads to hemolysis (2). Examples of the drugs that cause drug induced hemolytic anemia are Ibuprofen, Diclofenac, L-dopa, Procainamide (6).CAUSESIn majority of the cases AIHA is caused due to some primary underlying diseases like lymphoproliferative, autoimmune and infectious diseases (2). For example, after the M.suis infection in pigs, warm IgG autoantibodies are directed against the RBCs and destroys it. In this case actin was the active co mponent that played a vital mathematical function in inducing an autoimmune response. Actin acted as a target protein for the autoreactive antibody during the knifelike phase of the M.suis infection. The autoreactive antibody production is induced by a misguided upregulation of the of course occurring B cells specific for self antigens, appearance of previously cryptic antigens, occurance of change self antigens, tolerance to self antigens due to molecular mimicry. The autoimmune epitopes (in this case actin) on the RBCs may be due to contact with the proteolytic enzymes. Cytoskeleton of the RBCs gets modified by the attachment and invasion of the infectious cistron. Also the infectious agent causes damage to the RBCs making the hidden cytoskeletal proteins of the RBCs accessible for the circulating antibodies. due to all the above mentioned reasons the antibodies recognizes them as non-self and elicit an immune response (3).There are several other causes which may lead to AI HA other than due to a primary infections. For example higher incidence of occurance of AIHA after allogenic hematopoetic stem cell transplantation in adult patients. Further studies proved that the chances of increase of AIHA is more in patients with HSCT from unrelated donors and also that they develop chronic extensive ingraft versus host disease (GVDH). In such cases it was observed that AIHA was never the primary cause of death, rather it was due to infection of GVDH (5). In some rare cases, liver transplantation or solid organ transplantation leads to the development of AIHA (11)(14)(15).DIAGNOSISThe destruction or removal of red blood cells from the circulation ahead their normal life span of 120 days is called Hemolysis. Hemolysis manifests itself as acute or chronic anemia, reticulocytosis or jaundice. Intravascular hemolysis refers to the destruction of red blood cells in the blood with the release of contents into plasma. This is then followed by direct membrane degrad ation and cell destruction caused by automatic trauma from a damaged endothelium, complement fixation and activation on the cell surface. On the other hand, extravascular hemolysis refers to the removal and destruction of red blood cells with membrane alterations by the macrophages of the spleen and liver. The hemolysis can be categorized broadly into the following typesHEMOLYTIC ANEMIAHEREDITARY (6)ACQUIRED (6)(Due to infections (6)Microangiopathic (6)Autoimmune (6)Autoimmune (6)Alloimmune (6)Drug induced (2) (6)Paroxysmal(1)(2)(6)Mixed(1)(2)(3)(4)(6)Cold(1)(2)(3)(6)Warm(1)(2)(3)(6)Immune complex or Auto-antibody (6)Drug absorption (hapten induced) (6) hold up blood transfusion reaction (6)Acute transfusion reaction (6)Flow map 2 Broad classification of autoimmune hemolytic anemia.Since all the above said categories of hemolytic anemias have many similar symptoms and expressions, efficient diagnostic techniques should be veritable to detect the correct category of hemolytic anem ia for its appropriate treatment.DIAGNOSTIC TESTINGBasic diagnosis for hemolysis on the basis of laboratory and peripheral smear findingsHematologic testsReticulocytosis which is the normal response of the bone marrow to the peripheral loss of blood cells is an important feature of speech laboratory feature of hemolysis. Checking for the presence of reticulocytosis can be used for diagnosis of hemolysis. Review of the peripheral blood smear with an assessment for pathognomic red blood cell morphologies (spherocytes or schistocytes) along with examination of WBCs and platelets is very important for the rating of any anemia (6).Chemistry testsIncreased unconjugated bilirubin, increased lactate dehydrogenase, and decreased haptoglobin levels are characteristic feature of the distruction of RBCs and thus can be used for diagnosis of hemolysis (6).c) In addition to the above tests, urinary tests are also be performed (6)After diagnosis of the basic hemolysis, its etiology is opiniona ted by performing further diagnostic tests. This review article focuses on the diagnostic techniques specific for AIHA. Microspherocyte on a peripheral smear and controlling direct antiglobin test (DAT) is a characteristic feature of AIHA (1). The direct antiglobin test ,is also known as direct Coombs test (8). It demonstrates the presence of antibodies or complement on the surface of red blood cells which is the hallmark of autoimmune hemolysis (8). In this technique, the patients red blood cells are mixed with lapin or mouse antibodies against human IgG or C3. The test would generate a positivistic result if an agglutination reaction between the patients antibody or complement coated red blood cells by anti-IgG or C3 is observed. RBC agglutination with anti-IgG serum indicates warm AIHA and RBC agglutination with anti-C3 indicates the cold AIHA. besides further efficient and very specific diagnostic techniques should be developed to distinguish mixed AIHA and paraxysomal cold hemoglobinuria from the other types. Also the present diagnostic techniques many a times failed to give an errorless greenback between these two types of AIHA (4).The three types of drug induced anemia based on their mechanism of their mechanism of action can be find by a positive DAT and its type can be identified by the intravascular or extra-vascular hemolysis that it produces (6).TREATMENTTreatment mainly depends upon the type of AIHA i.e warm antibody type, cold antibody type, mixed antibody type or paraxysomal cold hemoglobinuria and also on the secondary or the idiopathic forms. The following are the treatment picks for AIHA. However each treatment stratergies has its own advantages and disadvavtages.Warm antibody autoimmune hemolytic anemia i) CORTICOSTEROIDSThe initial therapeutic agent used for treatment of WAIHA patients are the adrenal cortical steroids.There is a rapid onset of response. This therapy is usually maintained for 1-3 weeks, however sudden ceasation of th erapy may result in pep up relapse of hemolysis. The adverse effects of long term use of corticosteroids as a therapeutic agent would include pulmonary aspergellosis, central nervous system hemorrhage (2), osteoporosis, avascular necrosis, susceptibility to infection, abnormalities in glucose and lipid transfiguration and growth suppression in children (7).The gluocorticoids may inhibit antimicrobial activity of macrophages thus showing side effects when treated with it (2). In cases of pediatric anemia, prednisolone along with folic acid supplementation was used for therapy which showed a positive response in 81% of the patients (8).ii) SPLENECTOMYSplenectomy is mainly considered in patients who donot respond to the corticosteroid therapy. The main advantage of splenectomy is that it has a potence for a complete and long term remission. The adverse effect of spelectomy would include overwhelming postspelectomy infection (OPSI) which may result in serious morbity or mortality in a dwarfish percentage of patients after spelectomy (2)(7)(8).iii) IMMUNOSUPPRESSIVE DRUGSThis is the third therapeutic option after both corticosteroid therapy and spelectomy. Examples of the immuno-suppressive drugs would include azathioprine, cyclosporine (8), rituximab (9)(11) etc.iv) DANAZOLEIt is an attenuated androgen with good responses and comparatively lesser side effects (2)(7).v) INTRAVENOUS IMMUNOGLOBINIn patients who doesnot respond to the corticosteroids, it is used as a second line therapy. However, intravenous immunotherapy is expensive (2)(7).vi) PLASMA EXCHANGEUsed for acute reversal of severe hemolysis along with other therapeutic agents.Cold antibody autoimmune hemolytic anemiaThe simplest and the possible way for reducing the severity of CAIHA is avoidance of cold. plasma exchange showed a temporary benefit in a small percentage of patients. Any other therapeutic options involved more potential risks than probable benefits.Paroxysmal cold hemoglobinuriaIn mo st of the cases hemolysis terminates spontaneously and hence only supportive care is required. Sometimes transfusion of RBCs and corticosteroid therapy may have a positive impact on the treatment.Atmost care should be taken in case of secondary autoimmune hemolytic anemia i.e the underlying diseases like chronic lymphocytic leukemia, general lupus erytromatous, lymphomas etc should be treated for complete remission from AIHA (7).Combinational therapy was used in some cases of AIHA as secondary infection. Example, a case in which AIHA was found in association with Plasmodium vivax infection was treated with chloroquine and primaquine (for P.vivax infection), prednisolone and transfusion of least incompatible RBCs (for AIHA) (12).CONLUSIONThis review article gives a very short business relationship about autoimmunity as a disorder. It mainly focused on auto-immune hemolytic anemia which is a subset of autoimmunity. The types of AIHA, causes, diagnosis and possible treatment straterg ies were discussed. The future electron orbit of research under this topic is in finding out more efficient and specific diagnostic techniques to detect mixed and paroxysmal cold hemoglobinuria and treatment options with maximum results and minimum side-effects. Drugs like Bortizomib (13), Alemtuzumab (humanized monoclonal antibody targeting CD52 antigen) etc are still under research for the treatment of hemolytic anemia (16).