Cause Of Autoimmune Hemolytic Anemia Research Articles

Autoimmune Hemolytic Anemia in Treatment-Naïve Chronic Hepatitis C Infection

Purpose: Hepatitis C Virus (HCV) is a blood borne pathogen that infects the liver and is associated with great morbidity. Chronic HCV infection can lead to cirrhosis, hepatocellular carcinoma, and ultimately liver failure. Less commonly known extrahepatic manifestations of HCV exist as numerous studies have been published demonstrating Autoimmune Hemolytic Anemia (AIHA) in chronic Hepatitis C patients receiving Ribavarin or Interferon. On the contrary, there is minimal literature demonstrating AIHA in treatment-naive chronic hepatitis. Case Presentation: A 53-year-old man with chronic Hepatitis C infection presented with 7 days of sharp right upper quadrant abdominal pain complicated by rapidly increasing abdominal girth, nausea, vomiting, weakness, fever and jaundice. His HCV course was complicated by cirrhosis, esophageal varices, portal hypertensive gastropathy and spontaneous bacterial peritonitis. Physical examination: Jaundiced sleepy male with normal vital signs. Scleral icterus, distended abdomen tender to palpation in the right upper quadrant, gynecomastia, diffuse spider angiomata on anterior chest, and +2 bilateral pitting edema up to the knees. No asterixis, palmar erythema, or caput medusae. Laboratory data: WBC 5700/UL, Hemoglobin 8.3 g/dl, MCV 112.4, platelets 47,000/UL. Indirect bilirubin of 14.3 mg/dl was worrisome for hemolytic anemia. Reticulocyte count 9.6% and direct Coomb's test antibody positive. Peripheral smear showed increased spherocytes, polychromasia, and thrombocytopenia consistent with AIHA. Workup: Etiologies of AIHA include malignancy, SLE, Ribavarin and Interferon. MRI and CT abdomen with contrast illustrated cirrhosis, but did not depict neoplastic lesions or lymphadenopathy. Chest CT and x-ray demonstrated no neoplasms, mediastinal or axillary lymphadenopathy, and no changes of the bony thorax consistent with a cancerous process. Bone marrow biopsy demonstrated erythroid hyperplasia with cell lines. No tumor or lymphoma was noted. Thus, malignancy was ruled out as an etiology of AIHA. SLE was subsequently ruled out with a negative ANA panel, and iatrogenic etiology was non-contributory as the patient had never received Ribavarin or Interferon. Conclusion: We present a rare case of AIHA infection where conceivably all etiologies of AIHA were thoroughly ruled out - demonstrating HCV as a unique and novel cause of AIHA. This is of great interest in idiopathic AIHA, as physicians we can look to HCV as an underlying source of AIHA. More recently, HCV is becoming an epidemic in the United States. Thus, unprecedented medical conditions associated with HCV are of great interest.

Implication of oxidative stress as a cause of autoimmune hemolytic anemia in NZB mice

We have recently shown that deficiency of the superoxide dismutase 1 gene (SOD1) causes anemia and autoimmune responses against red blood cells (RBCs) and that transgenic expression of human SOD1 in erythroid cells rescues them. Because these phenotypes observed in SOD1-deficient mice are similar to autoimmune hemolytic anemia (AIHA), a causal connection between reactive oxygen species (ROS) and AIHA was examined using an AIHA-prone New Zealand Black (NZB) mouse. ROS levels in RBCs were high in young NZB mice, compared to control New Zealand White (NZW) mice, and increased during aging. Methemoglobin and lipid peroxidation products were elevated during aging, consistent with the elevated oxidative stress in RBCs of NZB mice. Severity of anemia and levels of intracellular ROS were positively correlated. Levels of antibodies against 4-hydroxynonenal and acrolein were also elevated in NZB mice. Transgenic expression of human SOD1 protein in RBCs of NZB mice suppressed ROS in RBCs and decreased the death rate. When RBCs from C57BL/6 mice were injected weekly into the same strain of mice, production of anti-RBC antibody was observed only in mice that had been injected with oxidized RBCs. Thus, oxidation-mediated autoantibody production may be a more general mechanism for AIHA and related autoimmune diseases.

Case Report: Hemolytic Anemia During Pegylated IFN-α2b 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.

Autoimmune hemolytic anemia.

Rh and ABO incompatibilities, drug reactions, and lupus are a few of the many causes of autoimmune hemolytic anemia. Among the determinants of autoimmunity involved are the class of the antibody, the biochemical composition of the antigen, the distribution of the antigen on the erythrocyte membrane, and the effector cells and molecules that are mobilized.

過去３年間における対象別赤血球抗体のひん度

Anti-erythrocyte antibodies were detected in 56 (0.99%) of 5619 patients with various diseases and most of them contained anti-Lewis, Rh and P1 antibodies.The antibodies were detected in 14 (5.3%) of 264 pregnant women and most of them contained anti-RhD and E antibodies. Moreover, the antibodies were detected in 33 (0.22%) of 14, 900 healthy blood donors, and most of them contained anti-Lewis and P1 antibodies.The other antibodies seemed to be natural antibodies of type IgM in all healthy blood donors expect three cases, of whom one had a history of blood transfusion and the other two had a history of pregnancy. Most of patients with unidentified antibodies were positive for direct Coombs test but in patients with negative direct Coombs test, the antigen-antibody reaction occurred at low temperature zone by using saline and 22% albumin methods.These results suggested that such methods as detecting anti-RhD, E Lewis and P1 antibodies should be used in the identification of anti-erythrocyte antibodies.Moreover, autoimmune hemolytic anemia (AIHA) characterised by positive direct Coombs test developed in a patient with severe epilepsy who had been administered a large amount of anti-epilepsy agents for long term. It was appeared that the cause of AIHA was due to phenitoin (Aleviatin) following clinical course. In case like this patient, all chemicals should be immediately discontinied and other drugs being different structures should be used property, also, hematological and immunological examination should be done.