Infantile giant cell hepatitis with autoimmune hemolytic anemia

Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically associated with autoimmune hemolytic anemia in the absence of any other systemic or organ-specific autoimmune comorbidity. The etiology is unknown; concomitant viral infections (as potential trigger factors) have been identified in a few patients. The pathogenesis reportedly relies upon immune-mediated/ autoimmune mechanisms. This condition should be considered in any infant developing Coombs-positive anemia; indeed, anemia usually precedes the development of hepatitis. The clinical course is usually aggressive without the appropriate immunosuppressive therapy, which may include steroids, conventional immunosuppressors (e.g., azathioprine and cyclophosphamide as first-line treatments), intravenous immunoglobulin, and biologics (rituximab). Improvements in medical management (including the availability of rituximab) have significantly reduced the mortality of this condition in the last decade.     

Refractory sideroblastic anemia secondary to autoimmune hemolytic anemia.

A 75-year-old woman was hospitalized with autoimmune hemolytic anemia. During a period of 22 months the patient had six hemolytic crises which responded to treatment with prednisone and azathioprine. During the last admission the patient presented a sideroblastic anemia with 98% of 'ring sideroblasts' in the bone marrow. This association has never, to our knowledge, been reported before. It is possible that the immunosuppression played a definite role in the development of this sideroblastic anemia.     

Grand rounds: autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AHA) may be either primary (ie, "idiopathic," one third of all patients) or secondary (ie, associated with underlying illness, two thirds of all patients). A positive Coombs antiglobulin test is the most important criterion for diagnosis of AHA, and characterization of RBC coating (as to whether it is by IgG alone, by IgG plus complement, or by complement alone) may be valuable in ruling out certain underlying illnesses as causative in selected patients. Many limitations to the antiglobulin test must be kept in mind. As routinely performed, a positive result requires greater than 500 molecules of IgG per RBC. Red blood cells from normal subjects have less than 35 molecules of IgG per RBC. Up to 2% to 5% of patients with AHA will have RBC coating in the 50 to 500 molecules per cell range and may therefore have "false"-negative antiglobulin tests. Apparent failures of strength of antiglobulin reactions to correlate with severity of in vivo RBC destruction may result from technical factors or may reflect intrinsic differences among autoantibodies (eg, IgG subclass, affinity). A likely mechanism of in vivo RBC destruction in AHA has been demonstrated in immune-mediated in vitro RBC "rosette" formation about macrophages and lymphocytes bearing specific receptors for subclasses of IgG and for subcomponents of complement. Increased avidity of macrophages for coated RBCs in response to such stimulus as infection may play an additional role. Treatment involves control of underlying disease and the judicious use of adrenal steroids, splenectomy, and immunosuppressive agents. Transfusions, while life-saving in life-threatening anemia, carry substantially increased risks in AHA patients. Their use should be strictly limited.     

Reticulocytopenia in autoimmune hemolytic anemia

1. In a series of 57 cases of autoimmune hemolytic anemia it was found that25 or 44 per cent had a relative reticulocytopenia at times of hemolytic crisis.The mortality rate in this group was significantly higher than in those whoshowed a reticulocyte response consistent with the severity of anemia. Specialsignificance is given to the high mortality rate among the patients with idiopathic AHA.

2. Four illustrative cases are presented.

3. There is a discussion of mechanisms that may be responsible for reticulocytopenia in the presence of severe anemia and erythroid hyperplasia of the marrow.

Submitted on January 23, 1956 Accepted on March 7, 1956     

Treatment of autoimmune hemolytic anemia

The appropriate therapy of autoimmune hemolytic anemia (AIHA) is dependent on the correct diagnosis and classification of this family of hemolytic disorders. Although the majority of cases are warm AIHA, there are several distinct types of cold AIHA and a number of drug-induced etiologies of AIHA, which must be investigated to determine if stopping a drug will induce a remission. In warm AIHA, corticosteroids are standard, followed by consideration of splenectomy in recalcitrant cases. If steroids and splenectomy are insufficient, other forms of immunosuppressive therapy are typically initiated. In cold AIHA, keeping the patient warm in often sufficient, but therapy directed at an underlying lympholiferative disorder may be helpful. Brisk hemolysis, inadequate responses to therapy, and worsening anemia require transfusion therapy. Although the pretransfusion workup is made difficult by the presence of the autoantibody, transfusion services can usually provide blood safe for transfusion by excluding underlying alloantibodies. When transfusion is urgently required and compatible blood cannot be located, incompatible blood may be provided as a life-saving measure. Communication between the transfusion service and the hematologist is critical to assess the risks in these settings. Hemoglobin-based oxygen carriers may provide an important bridging therapy in the future. Requests for "least incompatible" blood do not enhance transfusion safety and often result in unnecessary delays.     

Autoimmune pathogenesis and autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder in which autoantibodies are directed against an individual's own red blood cells (RBCs), leading to enhanced clearance through Fc receptor (FcR)-mediated phagocytosis. Although there is a large literature relating to clinical aspects of AIHA, relatively little work addresses how IgG autoantibodies are actually produced against RBC autoantigens. This review will first discuss the current understanding of autoimmunity in general and then focus on the knowledge of the immunopathogenic mechanisms responsible for autoantibody production in AIHA. Both human and animal studies will be discussed. Understanding theses mechanism is vital for developing antigen-specific immunotherapies to treat the disease.     

Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone

An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the β lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with β lactam antibiotics.     

Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia

Autoimmune hematologic abnormalities are not well recognized in chronic hepatitis C virus infection. We demonstrate an unusual association between primary autoimmune hemolytic anemia and chronic hepatitis C virus infection. A 69-year-old woman who had a history of hepatitis C virus-related liver cirrhosis was found to have deteriorating anemia with reticulocytosis when admitted to the hospital. Laboratory work revealed both positive direct and indirect Coombs' tests, and warm-type immunoglobulin G against surface antigens of red blood cells. After prednisolone therapy, her anemia improved dramatically. To our knowledge, this is the first reported case of chronic hepatitis C virus infection linked with autoimmune hemolytic anemia in its natural course, not related to prior interferon treatment. Our report suggests that isolated autoimmune hemolytic anemia may be one of the unusual hematologic manifestations of chronic hepatitis C virus infection.     

Danazol therapy for autoimmune hemolytic anemia

We evaluated the use of danazol in 15 patients with autoimmune hemolytic anemia of the warm antibody type. Danazol, 600 to 800 mg/d, was added to previous regimens or given initially in conjunction with high-dose prednisone treatment. Twelve patients with autoimmune hemolytic anemia associated with nonmalignant disorders or idiopathic autoimmune hemolytic anemia and 1 of 3 patients with underlying neoplasms showed a rise in hematocrit within 1 to 3 weeks. Thereafter, glucocorticoid doses were tapered to a minimum requirement or stopped. Once remission was sustained, the dose of danazol was reduced to 200 to 400 mg/d. Although levels of erythrocyte-bound IgG antibody and C3 decreased with therapy, only the decrease in C3 was statistically significant (p less than 0.05) in this limited study. Danazol was effective regardless of the severity of the disorder and success or failure of previous treatments. Danazol is valuable in the treatment of autoimmune hemolytic anemia and may be better suited than glucocorticoids for long-term management.