Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person’s own red blood cells (RBCs) cause them to burst (lyse), leading to. Autoimmune hemolytic anemia (AIHA) is an uncommon disorder characterized by hemolysis mediated by autoantibodies directed against. Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either.
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Autoimmune hemolytic anemia AIHA is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder.
Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test DAT still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way.
Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients.
However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood.
Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services. IHA is classified as either autoimmune, alloimmune or drug induced based on the antigenic stimulus responsible for the immune response.
Usually these autoantibodies are directed against high incidence antigens.
Anemia Hemolitik Autoimun
But, often they exhibit reactivity against allogenic red cells. The peak incidence snemia between 60 and 70 years of age and the frequency of the disorder is usually more in females than in males.
The male to female ratio is In contrast, alloimmune hemolytic anemia requires exposure to allogenic red cells, the sources being pregnancy, blood product transfusion and transplantation.
The resulting alloantibodies show no reactivity towards autologous red cells. Drug-induced antibodies can recognize either intrinsic red cell antigens or red cell-bound drugs.
Antibodies that avalah with intrinsic red cell antigens are serologically indistinguishable from autoantibodies, whereas antibodies that react against red cell-bound drug require the drug for hemolysis.
The pathogenesis hfmolitik IHA ultimately overlaps for these three classifications. The degree of hemolysis depends on characteristic of the bound antibody as well as the target antigen. Zutoimun antibodies are relatively poor activators of the classical complement pathway, but are easily recognized by the phagocytic cells.
On the other hand, IgM antibodies readily activate the classical complement pathway and produce cytolysis. First described by Coombs et al. Serological characterization of autoantibody helps to differentiate various types of AIHA and gives a better assessment to the clinician regarding the likely course of disease and the form of treatment to be given.
Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances
IgG subclass determination will depict more hemolotik the prognosis of the disease. Determination of the specificity of the autoantibody correlates the serum antibody with the antibody eluted from patient’s red cells.
The determination of thermal amplitude of the causative autoantibody correlates with the severity of the episodes of hemolysis in patients with AIHA following their exposure to warm or cold. Thirdly, when the rate of in vivo red cell destruction is greater than the rate of marrow compensation anemia develops.
Immune hemolysis in vivo begins with opsonization of red cells by autoantibody. It was observed by Sokol et al. A varying affinity of IgG subclass for Fc receptor has been noticed by Sokol et al. Multiple IgG coating red cells are one of the major causes of hemolysis. The more the molecules of IgG, the more the activation of complement, the more is the red cell destruction. Cases of Aadlah generally are classified according to the characteristic hdmolitik reactivity of the red cell autoantibody [ Table 1 ].
Occasionally patients have a combination of warm and cold autoantibodies. It was observed by Petz and Garratty in and Sokol et al. Lymphoproliferative disorders such as chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma and Waldenstorm’s macroglobulinemia adalag the leading causes of secondary cases. Cold-reactive autoantibodies cause two distinct clinical entities: The typical case of an infectious etiology involves mycoplasmal pneumonia or infectious mononucleosis in an anemiz or young adult.
Some of the patients with warm AIHA also possess a cold agglutinin. Drugs can produce hemolysis by both immune and non-immune mechanisms. Historically, alpha methyldopa and high dose penicillin were responsible for the majority of cases of drug-induced IHA. Typically patients insidiously develop anemic symptoms such as weakness, dizziness, fatigue and dyspnea anemka exertion; hemoligik less specific symptoms include fever, bleeding, coughing, abdominal pain and weight loss.
Patients with primary or secondary cold AIHA have a mild, chronic hemolytic anemia producing pallor and fatigue, however there is exacerbation of the condition in a cold environment.
Episodes of acute hemolysis with hemoglobinemia and hemoglobinuria are more common in the winter months.
Patients also present with acrocyanosis during the exacerbations. Some patients experience Raynaud’s phenomenon and rarely the red cell agglutination becomes significant enough to produce vascular occlusions with resulting necrosis.
Patients with mixed-type AIHA have a chronic course interrupted by severe exacerbations, which can result in severe anemia at times. These exacerbations do not appear to be associated with cold exposure and do not result in acrocyanosis or Raynaud’s phenomenon. In an Indian study, Das et al. All patients presented with symptoms of anemia; however, in secondary AIHA the symptoms of underlying disorders were predominant. Three of the 43 patients complained of passing dark urine [ Table 2 ].
Since the pathophysiology of CAS typically involves IgM autoantibodies and complement, patients almost exclusively have positive DAT with anti-C3 and polyspecific reagents and a negative result with anti-IgG.
The IgM autoantibodies dissociate from the red cells subsequent to C3 binding and hence are generally not detected in vitro.
Pathological cold autoantibodies are characterized by large thermal amplitude or a high titer, with thermal amplitude as the better predictor of hemolysis. In addition pathologic cold autoantobodies generally have a titer of greater than 1: PCH is caused by a biphasic IgG autoantibody Donath-Landsteiner antibody that fixes complement at low temperature but ultimately dissociates at a higher temperature.
As a result, the DAT is positive with anti-C3, but it is generally negative with anti IgG unless performed at colder temperatures. Mixed type AIHA produce difficulties with the antibody screening and cross matching due to its association with a number of underlying causes.
The red cell eluate typically indicates panreactive warm IgG autoantibody. The cold autoantibody usually exhibits specificity against I antigen, but reactivity against i has also been reported. Drug-induced AIHA is serologically indistinguishable from warm AIHA; a presumptive diagnosis can be made only if the patient responds to withdrawal of the drug.
The treatment of warm AIHA generally depends upon the severity of the hemolysis, though folic acid supplementation is recommended for all. If the bone marrow can compensate, then the patient can continue to be monitored. However, once anemia develops, glucocorticoids are the first-line treatment. Other therapies such as plasmapheresis, IVIG, danazol have been tried with variable success. Treatment for CAS is dependent on its etiology and severity.
With primary CAS, most patients only have mild anemia. Therefore, avoidance of cold exposure is the primary therapy which necessitates moving to a warmer climate in some patients. Generally extravascular hemolysis in CAS occurs in the liver, so splenectomy has only benefited those patients with IgG cold agglutinins.
For secondary CAS, treating the underlying disease is the main stay of treatment.
Autoimmune hemolytic anemia
Most wnemia of PCH are self-limited. Treatment is usually symptomatic and also includes keeping the patient warm. Patients generally respond to steroids and immunosuppressive agents and splenectomy has been successfully employed.
To optimize the recovery, the underlying diseases have to be treated as well. Usually within several days of discontinuing the drug, this type of AIHA gets resolved, occasionally adala may be required for complete resolution. RBC transfusion if needed should be given, however, these red cells autlimun be hemolyzed at a similar rate as the endogenous red cells particularly when donor unit is cross-match incompatible.
Although RBC transfusion is not a contraindication in AIHA, however its use should be limited to cases of life-threatening anemia or a high risk of cardiac or cerebrovascular ischemic events. The serologic work-up is made complicated by the panagglutinating warm autoantibodies that often mask the existing alloantibodies thus rendering cross-match incompatible.
If the patient has not been recently transfused and does not have a high titer autoantibody, autoadsorption techniques can eliminate the confounding autoantibody and andmia the risk. When transfusion is needed then the heemolitik incompatible unit should be issued and the infusion should be slow and carefully monitored.
Donor RBCs are destroyed at the same rate as autologous RBCs unless the autoantibodies exhibit specificity, in which case antigen-negative units should be transfused if available. In CAS, red cell transfusions are only indicated when there is a life-threatening anemia causing crisis.
Least incompatible units may have to be transfused to manage such patients. Most of the cold autoantibodies are directed against I antigen and I antigen negative donor units are extremely rare, so red cell transfusion may potentiate hemolysis.
Hemolysis can also be accelerated by complement present in the exogenous donor plasma; so washed red cell transfusion may reduce such risk. P antigen positive blood can be beneficial when a blood warmer is employed. In context to Indian scenario Das et al opined hmeolitik decision to transfuse in AIHA should be based on the clinical condition of the patient.
No critical patient should be denied blood transfusion due to serological incompatibility. Twenty four of their 59 patients received blood transfusion with mean 2. The main determinants of blood transfusion were the deranged hematological and biochemical hemolytic markers and all transfusions were uneventful. Mean number of alloadsorptions for complete autoantibody removal using PEG was 1. Garratty in also found that washing the patient’s red cells with ice cold saline, preferably in a refrigerated centrifuge, helps to keep low-affinity IgG bound hemolitk the RBCs.
Each has its own advantages autoiumn disadvantages. The manual method has the disadvantage that it is least auyoimun for detection of red cell bound Ig. Moreover, it requires meticulous washing of red cells, which can be cumbersome. The CAT is easy to perform as it avoids washing phase and is more sensitive zutoimun In an elaborate study conducted by Das et al.
Therefore, it can be concluded that AIHA is not uncommon and requires advanced, efficient immunohematological and transfusion support.