A case of autoimmune hemolytic anemia associated with an ovarian teratoma

Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect antiglobulin tests were all positive. The abdominal computed tomography scan revealed a huge left ovarian mass, and this indicated a teratoma. She was refractory to corticosteroid therapy; however, after surgical resection of the ovarian mass, the hemoglobin level and the reticulocyte count were gradually normalized. The mass was well encapsulated and contained hair and teeth. She was diagnosed as having autoimmune hemolytic anemia associated with an ovarian teratoma. To the best of our knowledge, this is the first such a case to be reported in Korea.     

Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A

Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.     

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.     

Multiple nodular and patchy shadows in chest radiograph in a patient with autoimmune hemolytic anemia associated with chronic thyroiditis]

A 65-year-old woman was admitted because of dyspnea and persistent cough. Her chest radiograph and CT films revealed multiple nodular and patchy shadows in bilateral lungs, indicating bronchiolitis obliterans organizing pneumonia (BOOP)-like shadows. Autoimmune hemolytic anemia was diagnosed because peripheral blood cell analysis revealed anemia (hemoglobin, 5.5 g/dl) with increased reticulocytes (253/1000), and positive direct and indirect Coomb's tests. In addition, decreased diffusion capacity and mild hypoxemia (PaO2, 71 Torr) were recognized. Bronchoalveolar lavage fluid (BALF) showed the increased number of total cells and lymphocytes, and a decreased CD4(helper)/CD8(suppressor) ratio (= 0.65). Histopathological features of transbronchial lung biopsy showed an infiltration of lymphocytes in the alveolar walls and spaces, and thickening of the alveolar walls. A discrepancy was apparent among roentgenogram, histopathological findings and BALF results. Open lung biopsy had not been performed because of severe hemolytic anemia and lack of informed consent. In addition, the patient suffered from chronic thyroiditis with positive thyroid autoantibody. After oral administration of prednisolone, both pulmonary shadows and anemia improved. We concluded that autoimmune hemolytic anemia may be associated with steroid-sensitive interstitial lung lesions in some cases. Further immunologic studies are necessary to elucidate the relationship between autoimmune hemolytic anemia and interstitial lung shadows.     

Accompanying hemolysis in lymphoproliferative diseases

149 patients with non Hodgkin lymphomas (NHL) were observed at the III. Medical Department of the Hanusch Hospital during 1972--1978. 15 out of 106 patients with low malignant NHL had autoimmune hemolytic anemia (AHA). None of the patients with high malignant NHL showed evidence of hemolysis. In 10 cases AHA was diagnosed together with the lymphoproliferative disease. In 4 cases diagnosis of AHA and NHL was established at the same time and in only 1 patient diagnosis of AHA preceded the lymphatic disease. All patients had distinct signs of hemolysis with moderate to severe anemia. 4 patients with immunocytic lymphomas had IgM paraproteins and an elevation of gamma-globulins, all other patients had mild to severe hypogammaglobulinemia. Therapy in all cases consisted of corticosteroids and cytostatics (Chlorambucil, Cyclophosphamide). In none of our cases splenectomy was performed. AHA seems to be a bad prognostic factor in patients with chronic lymphocytic leukemia. Survival time in patients with chronic lymphocytic leukemia and AHA was 18 months shorter than in all other patients suffering from chronic lymphocytic leukemia.     

Evidence in favor of a role of idiotypic network in autoimmune hemolytic anemia induction: theoretical and experimental studies

Formation dynamics of antibodies to rat erythrocytes (REs) and auto-antibodies to mouse erythrocytes were studied in an experimental model of autoimmune hemolytic anemia (AHA) in mice. The experimental conditions of AHA were simulated in a mathematical model of an immune network. It was found that maximal production of auto-antibodies and antibodies to REs do not synchronize. Antiserum, obtained at the peak of auto-antibodies formation, competed with REs for bounding with antibodies. This represents proof that auto-antibodies to erythrocytes and antibodies to REs are an idiotype-anti-idiotypic pair. In the autoimmune reaction, the autoreactive clone, being anti-idiotypic, responded earlier than the clone reacting to the injected antigen. Comparison of autoimmune reaction kinetics in the mathematical model of an immune network with experimental dynamics of AHA shows them to be similar. So activation of the autoreactive clone to erythrocytes during experimental AHA in mice is mediated by idiotype-anti-idiotypic interactions with the clone reacting to REs.     

Autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AHA) is characterized by the production of Coombs' antibodies, which are responsible for the destruction of red blood cells (RBCs). Analysis of both monoclonal anti-RBC autoantibodies derived from autoimmune New Zealand black mice and transgenic mice expressing a pathogenic IgM anti-RBC autoantibody has considerably improved our understanding of the B-cell responses involved in AHA, although our knowledge of T-cell immunity in AHA is still limited. The identification of the major T-cell epitope in the context of MHC class II molecules would be of paramount importance in helping to elucidate the cellular and molecular basis central to the development of AHA.     

Autoimmune hemolytic anemia in Philadelphia positive chronic myeloid leukemia with t(7;14) anomaly after 5 years of interferon alpha treatment

A 41-year-old woman, Philadelphia positive chronic myeloid leukemia patient, had progressive decline in hemoglobin levels. She had been receiving interferon alpha treatment for five years. Autoimmune hemolytic anemia was diagnosed. Subsequent bone marrow examination revealed translocation t(7;14). She was placed on prednisone treatment. The patient responded to prednisone as treatment for the hemolytic process. The result of a direct Coombs' test remained positive. The patient died shortly after the diagnosis of autoimmune hemolytic anemia. Autoimmune hemolytic anemia should be considered in the evaluation of chronic myeloid leukemia patients with a sudden decrease in hemoglobin levels.     

Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.     

Autoimmune hemolytic anemia associated with postirradiation malignant stromal tumor (leiomyosarcoma) of the jejunum

We describe a patient who presented with autoimmune hemolytic anemia and small bowel obstruction secondary to a malignant stromal tumor (leiomyosarcoma) of the jejunum, 25 years postchemotherapy and radiation treatment for stage IIA Hodgkin's disease. The patient was treated with corticosteroid therapy and surgical resection of the jejunal tumor. We conclude that autoimmune hemolytic anemia may be an unusual presentation for postirradiation sarcoma.     

Cold agglutinin disease after chicken pox. An uncommon complication of a common disease.

Chicken pox, although common, is rarely associated with autoimmune hemolytic anemia. Reported here is the case of an 8-year-old boy who was found to have cold agglutinin disease and severe anemia several days after he contracted chicken pox. The cold agglutinin appeared to be a polyclonal immunoglobulin M antibody with anti-Pr specificity. To our knowledge, this is the fifth reported case of autoimmune hemolytic anemia and the second reported case of cold agglutinin disease with anti-Pr specificity to be associated with chicken pox.     

Autoimmune hemolytic anemia in Gaucher's disease

Summary A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed.     

Macroglobulinemia Waldenstr?m complicated by autoimmune hemolytic anemia, meningeal sign and femoral lysis.

A necropsied case of macroglobulinemia Waldenstr?m with unusual complications was presented; the patient was found to have autoimmune hemolytic anemia, first. During the course of its treatment, he developed monoclonal immunoglobulin M in serum together with lytic osseous lesion in both femurs, and died of meningeal involvement by tumor cells. Clinically, he had hepatosplenomegaly and generalized lymphadenopathy. The macroglobulin was kappa type of light chain, ultracentrifugation showed sharp spike of 21S in 18.6%, and myelogram revealed increased lymphocytoid series of 29.6%. It was proved that autoantibody causing autoimmune hemolytic anemia was composed of IgG and macroglobulin itself had no activity as an anti-red cell antibody. An emphasis was made that autoimmune hemolytic anemia followed by macroglobulinemia is based on the state of immunodeficiency of this patient.     

Severe hemolytic anemia due to auto anti-N

Auto anti-N is infrequently encountered and, in most reported cases, does not cause clinical hemolysis. This case reports an auto anti-N associated with severe hemolytic anemia (Hb=2.7 g/dL) in a 6-year-old Caucasian girl with a history of vomiting, fever, and abdominal pain. Upon admission, she was found to have a metabolic acidosis, secondary to her severe anemia, with abnormal liver function tests. As in three other case reports, the autoimmune hemolytic anemia resolved, with disappearance of the auto anti-N, after corticosteroid therapy.     

Autoimmune hemolytic anemia as a manifestation of T-suppressor-cell deficiency

This report describes two children in whom autoimmune hemolytic anemia was the initial clinical manifestation of an underlying T-cell deficiency. Further investigation revealed a profound deficiency of T suppressor cells in both children as detected by monoclonal T-cell antibody (OKT8) and/or functional assays. In vitro incubation of their lymphocytes with cultured thymus epithelium or thymic factors induced T suppressor cells. In vivo treatment with cultured thymus epithelium or calf thymosin fraction 5 resulted in increased T-suppressor-cell numbers and/or function in both and possibly decreased hemolytic activity in one. These results suggest that the autoimmune process in some patients with autoimmune hemolytic anemia is associated with T-suppressor-cell deficiency and that in vivo therapy with agents that modulate T-cell function may be of therapeutic value.     

Bilateral congenitally bicuspid aortic and pulmonic valves: a rare entity

We present a case of a 70-year-old man who presented to hospital with autoimmune hemolytic anemia, who was found, incidentally, at postmortem, to have bilateral bicuspid aortic and pulmonic valves.     

Clinical correlation of positive direct antiglobulin tests in patients with sickle cell disease

Serologic findings of immune-mediated hemolytic anemia (autoimmune hemolytic anemia and cold agglutinin disease) are not infrequent in patients with sickle cell disease and can he clinically significant. Features of sickle cell disease that may affect the emergence and intensity of immune-mediated hemolysis include the antigenic stimulation of chronic red blood cell (RBC) transfusions, increased autoantibody production, RBC membrane defects, and functional asplenism. We describe two patients with sickle cell disease and serologic findings of autoimmune hemolytic anemia, but only one had increased RBC destruction attributed to the autoantibody. That patient's RBCs had IgG and complement on the surface, while those of the other patient had IgG without complement. Functional asplenism may diminish the role of an IgG autoantibody that does not hind complement, since RBCs coated with complement are removed by the liver. Therefore, complement-binding autoantibodies may have particular significance in immune-mediated hemolysis in patients with sickle cell disease.     

MACROGLOBULINEMIA WALDENSTRUM COMPLICATED BY AUTOIMMUNE HEMOLYTIC ANEMIA, MENINGEAL SIGN AND FEMORAL LYSIS

A necropsied case of macroglobulinemia Waldenström with unusual complications was presented; the patient was found to have autoimmune hemolytic anemia, first. During the course of its treatment, he developed monoclonal immunoglobulin M in serum together with lytic osseous lesion in both femurs, and died of meningeal involvement by tumor cells. Clinically, he had hepatosplenomegaly and generalized lymphadenopathy. The macroglobulin was kappa type of light chain, ultracentrifugation showed a sharp spike of 21S in 18.6%, and myelogram revealed increased lymphocytoid series of 29.6%. It was proved that autoantibody causing autoimmue hemolytic anemia was composed of IgG and macroglobulin itself had no activity as an anti-red cell antibody. An emphasis was made that autoimmune hemolytic anemia followed by macroglobulinemia is based on the state of immunodeficiency of this patient.     

A pilot study of eicosapentaenoic acid therapy for ribavirin-related anemia in patients with chronic hepatitis C

One of the major side effects of ribavirin/interferon alpha combination therapy for chronic hepatitis C is hemolytic anemia. One of the causes of hemolytic anemia is considered to be decreasing deformability of erythrocytes resulting from the accumulation of phosphorylated ribavirin in erythrocytes. The administration of eicosapentaenoic acid (EPA), which has a wide variety of pharmacological actions, increases the deformability of erythrocytes. We conducted an uncontrolled pilot study of EPA therapy for patients with ribavirin-related anemia. Six patients with chronic hepatitis C, who had developed anemia while receiving combination therapy, were treated with an oral ethyl ester of EPA (1800 mg/day) for two months. The hemoglobin level of all six patients increased following EPA therapy. The mean hemoglobin level significantly increased from 10.8 g/dl to 11.4 g/dl one month after therapy was initiated (P<0.05), and this level was obtained again one month later (11.5 g/dl). None of the patients developed an adverse reaction. These findings suggest that EPA has a beneficial effect in patients with ribavirin-related anemia. Further study is required to confirm our results.     

Morphological changes in the thymus in experimental autoimmune hemolytic anemia

Morphological changes in the mouse thymus in the experimental autoimmune hemolytic anemia were correlated with the results of the study of the immune status. The epithelial component of the thymus was more involved in the response to the experimental autoimmune hemolytic anemia during the whole experiment; this allows one to assume that just this component predetermines the character of this autoimmune process.