Clinical Characteristics and Treatment Outcomes of Patients With Autoimmune Hemolytic Anemia

Hemolysis is the premature destruction of erythrocytes. A hemolytic anemia will develop if bone marrow activity cannot compensate for the erythrocyte loss. The severity of the anemia depends on whether the onset of hemolysis is gradual or abrupt and on the extent of erythrocyte destruction Hemolysis can be due to hereditary and acquired disorders. Acquired causes of hemolysis include immune disorders, Toxic chemicals and drugs, Antiviral agents and Physical damage .

Autoimmune hemolytic anemia (AIHA) exhibits two important characteristics: shortened red blood cell (RBC) survival and presence of autoantibodies directed toward autologous RBCs, usually demonstrated by a positive direct antiglobulin (Coombs) test (DAT). AIHA is classified by the temperature at which autoantibodies bind optimally to RBCs. In warm antibody AIHA, which constitutes about 80-90% of adult cases, hemolysis is mediated by antibodies which bind to RBCs at 37 °C (98.6 °F. In cryopathic hemolytic syndromes, cold-reactive autoantibodies exhibit affinity for RBCs optimally at temperatures below body temperature. In adults, most of the cold-reactive antibodies are agglutinins of the immunoglobulin M (IgM) isotype. In children, cold hemolysins (generally IgG) are most common. Unusual patients with mixed AIHA exhibit both cold-reactive and warm-reactive autoantibodies .

Each of these types of AIHA may be sub-classified based on the presence or absence of underlying diseases. In the absence of an underlying disease, the AIHA is termed primary or idiopathic. When AIHA occurs as a manifestation or complication of another disease, the term secondary AIHA is used. Chronic lymphocytic leukemia (CLL) and lymphomas account for about half of all secondary AIHA cases. Systemic lupus erythematosus (SLE) and other autoimmune diseases also account for a large number of secondary AIHA cases. Certain drugs also mediate immune injury to RBCs. Three mechanisms are recognized and two of these involve elements of autoimmunity, in which autoantibodies recognize and bind to specific RBC epitopes in concert with drugs or their metabolites or in which the autoantibody binds to RBC epitopes without the presence of drug

Diagnosis The signs and symptoms of AIHA are nonspecific and common to all types of anemia . The primary symptoms include exertional dyspnea, dyspnea at rest, varying degrees of fatigue, and signs and symptoms of the hyperdynamic state, such as bounding pulses, palpitations…etc

The laboratory findings of drug-induced AIHA may resemble those of warm antibody AIHA or a cryopathic hemolytic syndrome, depending on the mechanism of the autoantibody induction and the target antigen. A high index of suspicion on the part of the clinician and discussions with blood bank personnel can usually reveal the role of the drug.

complete blood count Peripheral blood smear : This test can detect an anemia, pancytopenia, and infections. Along with the differential count, a complete blood count can help diagnose hematologic malignancies and other hematological disorders. The platelet count usually is normal in most hemolytic anemias.

An increased reticulocyte count represents increased RBC production and is a criterion for hemolysis but is not specific for hemolysis. Thrombocytopenia associated with positive direct coombs test occur in evans syndrome .

Serum lactate dehydrogenase (LDH) study : Serum LDH elevation is a criterion for hemolysis, but is not specific

Serum haptoglobin : A low serum haptoglobin level is a criterion for moderate-to-severe hemolysis.

Indirect bilirubin : Unconjugated bilirubin is a criterion for hemolysis, but it is not specific , the level of indirect bilirubin usually is less than 3 mg/dL.

Direct antiglobulin test (DAT):

The DAT result is usually positive in autoimmune hemolytic anemia (AIHA), but it may occasionally be negative in this disorder. DAT-negative AIHAs have been reviewed. From 5-10% of all AIHAs are DAT negative. The polybrene test can detect DAT-negative AIHA.

Treatment all of the drugs used in the treatment of AIHA are largely or partly directed against the patient's natural immune system, which may, in turn, extensively derail the immune system due to treatment. .The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In coronary artery disease , rituximab is now recommended as first-line treatment