الفهرس 
ErythropoiesisOnly 14 pages are availabe for public view
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Abstract
AIHA is an acquired immunologic disease in which the patient’s RBCs are selectively attacked and destroyed by autoantibodies produced by the patient’s own immune system. These patients generally display the common symptoms of anemia as weakness, pallor, fatigue, and jaundice. Less obvious is that frequent occurrence of mild splenomegaly. Peak incidence is among pre-school aged children. It is more common among adolescent female patients.
AIHA is classified into warm type, cold agglutinin syndrome, mixed type AIHA, paroxysmal cold hemoglobinuria, and drug induced AIHA. Characteristics of the autoantibodies are responsible for the various clinical entities. As a result, diagnosis is based on the clinical presentation and a serologic work up.
AIHA is most often idiopathic and it may be secondary to malignancies, autoimmune disorders, transfusion reaction, viral infection and drug usage.
In idiopathic AIHA, hemolytic anemia, anemia is the only clinical finding and no underlying systemic disease is observed that could explain the presence of autoantibodies. Secondary AIHA occurs associating a systemic disease, and the hemolytic anemia is just one manifestation of that disease.
Patients usually pre¬sent with symptoms of anemia, hemolysis and manifestations of the underlying disease. The degree of hemolysis depends on the characteristics of the bound antibody, i.e. its quantity, specificity, thermal aptitude and ability to fix complement and bind tissue macrophages.
The diagnosis of AIHA requires evidence of anemia, haemolysis and demonstration of autoantibodies attached to the patient’s RBCs (i.e., a positive DAT).
Typical patients exhibit anemia, reticulocytosis, spherocytosis and/or red cell agglutination and polychromasia on the blood film. Increased indirect serum bilirubin, urinary urobilinogen, serum LDH and low haptoglobin are also positive in AIHA.
The most important immunological test that can be done is the direct and antiglobulin test (DAT). Positive DAT is the corner stone of diagnosis in AIHA. The DAT is used to detect antibody or complement attached to RBCs. It involves red cell wash followed by incubation with AHG. The AHG reagent must contain antibodies against IgG and C3d complement component. Broad spectrum AHG reagents may contain Abs against other serum proteins that can bind nonspecifically to RBCs. Positive DAT includes a variety of causes such as the presence of auto-Abs in immune mediated hemolytic anemia or alloantibodies after incompatible blood transfusion. Also, non specific adsorption of proteins such as in patients with myeloma or hyper gammaglobulinemia may result in false positive DAT.
Negative DAT in a patient with clinical picture of AIHA could be due to low level of Abs on RBC surface or low sensitivity of DAT. About 7% of cases may be presented with negative DAT on repeated testing, so other laboratory tests must be used for detection of RBC-bound IgG with negative DAT which include; radio-immunoassay, enzyme linked antiglobulin test, complement fixation antiglobulin consumption assay, flowcytometry, direct polybrene test, direct polyethylene glycol test, preparation of concentrated elute from the RBCs, a monocyte monolayer assay and ELISA. About 34% of patients with AIHA and negative DAT would be positive by at least one of these methods. However, no one test was optimal and a battery of tests seems to be the most efficient approach.
However, false negative DAT may be due several technical errors including; improper red cell wash, excessive agitation at the reading step and the use of improper antisera.
A more detailed characterization of the Ig class involved in the AIHI regarding its specificity and complement involvement in hemolytic process are also important in guiding the diagnosis and management of individual patients
Also it is important to analyze the type and degree of erythrocyte damage during different periods of AIHA and examine their density and deformability which are helpful in the program of diagnosis and treatment.
The most common complications of AIHA are thrombo-embolim which may lead to pulmonary emboli, infection, cardiovascular collapse, deep vein thrombosis and splenic infarcts. So the proper diagnosis and treatment is necessary.
Strategies for the treatment of AIHA anemia include; immune suppressive therapy, treatment of the underlying condition, elimination of drugs or other causes and blood transfusion.
Patients with symptomatic AIHA require transfusion of RBCs. Finding compatible units for patients with broad specificity warm autoagglutinins is virtually impossible. “Least compatible” units may be selected for transfusion. Restrictive transfusion practice in WAIHA is recommended. Adequate pre-transfusion testing is required before transfusion. Plasma pheresis can be done for fulminate cases of AIHA with rapidly progressing disturbance of consciousness
Most patients with AIHA respond well to prednisone or prednisone and splenectomy which may provide long term remission. Intravenous immunoglobulin, immunosuppressive drugs and danazol have been effective in refractory cases and for patients who are poor candidates for surgery.
Cytotoxic drugs such as cyclophosphamide have been used to treat refractory cases of AIHA in an attempt to suppress auto-Ab synthesis. Mono-clonal Abs such as ritoximab (antiCD20) may also be used in this respect.
Other recent therapies include other monoclonal antibodies and anti IL-10 and anti IL-6.
In conclusion, AIHA is a clinical condition that results in anemia which may be acute and even life threatening. So, proper diagnosis and management is essential. Discrimination between various types and identification of the underlying cause is mandatory for planning proper therapeutic strategy.