Autoimmune hemolytic anemia

BASIC INFORMATION
Autoimmune hemolytic anemia is anemia secondary to premature destruction of red blood cells caused by the binding of autoantibodies and/or complement to red blood cells. Alloimmune hemolytic anemia occurs following blood transfusions due to transfusion of incompatible blood, to immunization by multiple previous transfusions, or during pregnancy, usually by Rhesus immunization of the mother. In autoimmune hemolysis, an unstable balance between cell destruction and regeneration is often present, which may worsen rapidly, leading to severe anemia and death.

EPIDEMIOLOGY & DEMOGRAPHICS
Autoimmune hemolytic anemia is most common in women <50 yr.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
Suspicion of an immune hemolytic process may arise from a routine blood count, if a fraction of microcytic hyperchromic erythrocytes is present. These cells appear as microspherocytes in the blood smear. Especially with IgM autoantibodies, erythrocyte agglutination is visible in the blood smear. So-called cold agglutinins, which usually are of the IgM type, may also cause acral necroses (Fig. 3.5). In this situation antierythrocytic antibodies must be sought using the Coombs test. If it is positive, then a diagnosis of autoimmune hemolytic anemia is established.
• Pallor
• Tachycardia
• Hepatomegaly, splenomegaly

Fig. 3.5 Necrotic spots on the fingers in a 61-year-old woman with cold agglutinin disease.

ETIOLOGY
Autoimmune hemolytic anemia is often secondary, therefore an underlying cause should be sought. A medical history and physical investigation aimed at the diseases mentioned in Tab. 3.7 should be performed. In addition, a bone marrow examination to exclude a lymphoma or multiple myeloma, serologic tests for lupus erythematosus, and radiologic examinations searching for enlarged lymph nodes and splenomegaly should be performed. A self-limiting, though severe, autoimmune hemolysis with cold-acting IgM antibodies may occur after infections with Mycoplasma pneumoniae or Epstein-Barr virus (mononucleosis). Drugs that have been repeatedly described as provoking an autoimmune hemolytic anemia are: a- methyldopa, penicillin, cephalosporins, tetracycline, tolbutamide, chinidin, and stibophen. For a number of other medications, case reports have been published with variably convincing evidence of causality.
• Warm antibody mediated: IgG (often idiopathic or associated with leukemia, lymphoma, thymoma, myeloma, viral infections, and collagen-vascular disease)
• Cold antibody mediated: IgM and complement in majority of cases (often idiopathic, at times associated with infections, lymphoma, or cold agglutinin disease)
• Drug induced: three major mechanisms:
1. Antibody directed against Rh complex (e.g., methyldopa)
2. Antibody directed against RBC-drug complex (hapten-induced, e.g., penicillin)
3. Antibody directed against complex formed by drug and plasma proteins; the drug-plasma protein-antibody complex causes destruction of RBCs (innocent by-stander, e.g., quinidine).
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Hemolytic anemia caused by membrane defects (paroxysmal nocturnal hemoglobinuria, spur-cell anemia, Wilson’s disease)
• Non-immune mediated (microangiopathic hemolytic anemia, hypersplenism, cardiac valve prosthesis, giant cavernous hemangiomas, march hemoglobinuria, physical agents, infections, heavy metals, certain drugs [nitrofurantoin, sulfonamides])
WORKUP
Evaluation consists primarily of laboratory evaluation to confirm hemolysis and to exclude other causes of the anemia.
LABORATORY TESTS
• Initial laboratory tests: CBC (anemia), reticulocyte count (elevated), liver function studies (elevated indirect bilirubin, LDH), evaluation of peripheral smear, Coombs’ test (positive direct Coombs’ test indicates presence of antibodies or complement on the surface of RBC, positive indirect Coombs’ test implies presence of anti-RBC

Table 3.7 Causes of secondary autoimmune hemolytic anemia

antibodies freely circulating in the patient’s serum), haptoglobin level (decreased)
• IgG antibody and IgM antibody
• Hepatitis serology, ANA
IMAGING STUDIES
• Chest x-ray
• CT scan of chest and abdomen to rule out lymphoma should also be considered
TREATMENT
NONPHARMACOLOGIC THERAPY
• Discontinuation of any potentially offensive drugs
• Plasmapheresis-exchange transfusion for severe life-threatening cases only
• Avoid cold exposure in patients with cold antibody
ACUTE GENERAL Rx
• Prednisone 1 to 2 mg/kg/day in divided doses initially
• Splenectomy in patients responding inadequately to corticosteroids when RBC sequestration studies indicate splenic sequestration
• Immunosuppressive drugs and/or immunoglobulins only after both corticosteroids and splenectomy (unless surgery is contraindicated) have failed to produce an adequate remission
• Danazol, usually used in conjunction with corticosteroids (may be useful in warm antibody autoimmune hemolytic anemia)
DISPOSITION
Prognosis is generally good unless anemia is associated with underlying disorder with a poor prognosis (e.g., leukemia, myeloma).