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.     

Corticosteroid treatment of pure red cell aplasia in a patient with hepatitis A

Secondary pure red cell aplasia (PRCA), as an extrahepatic manifestation of hepatitis A virus infection, has been reported on rare occasions. We report herein an unusual case of hepatitis A complicated by PRCA. In addition, we reviewed nine cases reported in the English literature. Our case of nonfulminant hepatitis A complicated by PRCA and hemolytic anemia was successfully treated with initial transfusion and corticosteroid therapy for 18 weeks. The patient's hematologic abnormalities and liver function tests re-normalized completely. We review clinical features and effective therapeutic strategies for this disease entity.     

Acute Parvovirus B19 Infection Leading to Severe Aplastic Anemia in a Previously Healthy Adult Female

Human Parvovirus B19 has been linked to a variety of diseases. One of the most common complications is transient aplastic crisis in patients with chronic hemolytic anemia. Very few case reports have implicated this virus as a putative etiology behind hepatitis and severe aplastic anemia in immuno competent individuals. We report a case of severe aplastic anemia in a previously healthy adult female due to acute parvovirus B19 infection. Laboratory examination showed pancytopenia in peripheral blood and severe hypoplastic bone marrow on biopsy. Serological analysis (ELISA) revealed acute Parvovirus B19 infection. In the face of unavailable HLA matched bone marrow donor, immuno-supressive therapy was contemplated, but could not be given because of financial constraints. Pancytopenia persists till date, 4 months after the diagnosis, with the patient requiring repeated packed red cell and irradiated platelet transfusions. Thus, acute infection with this virus must be considered a cause of acquired aplastic anemia even in individuals without underlying disease.     

Aplastic anemia and non-A, non-B hepatitis

Severe aplastic anemia is a rare but important complication of hepatitis. The agent(s) responsible for the hepatitis in these cases have not been well defined. Sixteen patient with hepatitis-associated aplastic anemia were studied for evidence of recent infection with hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and Toxoplasma. Results were compared with data from 10 randomly selected patients with aplastic anemia unassociated with hepatitis. Of the 16 patients, recent acute hepatitis A infection could be excluded in at least 14 patients. Hepatitis B surface antigen (HBsAg) was present in only one patient. A diagnosis of recent hepatitis B infection could not be excluded with confidence in two others. Tests for cytomegalovirus, Epstein-Barr virus, and Toxoplasma gave negative results. No patient with aplasia unassociated with hepatitis had evidence of recent hepatitis A infection, and the frequency of hepatitis B antibodies in this group was indistinguishable from that in patients with hepatitis. These data indicate that most cases of hepatitis that preceded aplastic anemia were not caused by hepatitis A virus or hepatitis B virus; non-A, non-B agents were probably involved in at least 13 of the 16 cases studied.     

Novel cytomorphology of the giant proerythroblasts of parvovirus B19 infection

The morphology of the giant proerythroblasts (GPE) in air-dried and Wright-Giemsa-stained smears of bone marrow in 16 patients with pure red cell aplasia (PRCA) caused by parvovirus B19 infection is described. B19 infection was diagnosed by the presence of the virus or viral DNA and/or IgM antibodies. Twelve patients had chronic hemolytic anemia and aplastic crisis and 4 patients had AIDS with chronic PRCA. In patients with chronic hemolytic anemia and aplastic crisis, GPE were not detectable in bone marrow biopsies that showed any degree of recovery of erythropoiesis. The GPE morphology was quite variable. The early (basophilic) GPE measured 25 to 35 μm in diameter, had a narrow rim of intensely blue and often vacuolated cytoplasm with pseudopodia, round nuclei with compact uncondensed chromatin, and an indistinct and inclusion-like purple-colored tinctorial change. The “intermediate” and “late” GPE measured 25 to 45 μm in diameter and showed cytoplasmic swelling, gradual loss of cytoplasmic basophilia, and fraying of the cytoplasm with focal rupture; the nuclei showed an increase in volume, a highly uncondensed and coarse sieve-like chromatin, and 1 to 3 prominent, pale to moderate purple inclusion-like nucleoli or inclusions. Bare nuclei similar in size and chromatin pattern to those of the GPE were present in proximity to the GPE and may have arisen from the GPE by dissolution of the cytoplasm. The glassy intranuclear inclusions with central clearing, the so-called lantern cells described in formalin-fixed tissues of patients with B19 infection, were absent in all cases. These findings suggest that direct toxic cell injury rather than apoptosis may be involved in the pathogenesis of erythroid aplasia in B19 infection. Am. J. Hematol. 58:95–99, 1998. © 1998 Wiley-Liss, Inc.     

Autoimmune hemolytic anemia in treatment-naïve chronic hepatitis C infection

Extrahepatic immunologic abnormalities have been shown to occur in patients with chronic hepatitis C virus (HCV) infection. Induction of autoimmune hemolytic anemia has been reported, either during or after interferon treatment of HCV infection. I report a 48-year-old patient with HCV infection who developed Coombs-positive autoimmune hemolytic anemia in the absence of treatment with interferon, with a review of the available literature. Other potential etiologies of autoimmune hemolytic anemia were ruled out. Prednisone therapy was instituted because of the severity of the fall in the hemoglobin. There was resolution of the hemolytic anemia and the prednisone was tapered gradually. No deterioration of the underlying HCV liver disease was evident even though an increase in HCV viremia was noted. Coombs-positive autoimmune hemolytic anemia can occur as an extrahepatic immunologic abnormality in treatment-na?ve patients with chronic HCV infection.     

Aplastic crisis caused by B19 virus in a child during induction therapy for acute lymphoblastic leukemia

A child undergoing induction therapy for acute lymphoblastic leukemia suffered an aplastic crisis associated with B19 virus infection. Good response to the antiblastic therapy led to a burst in erythropoiesis favoring high viral replication, which was responsible for strong erythroblastic inhibition and severe viremia. The patient's B19 antibody response became evident very late, probably because of the antiblastic effect of the therapy; nevertheless, recovery was complete in little more than a week, favored by B19 IgG transfusion with a red blood cell concentrate. This report suggests that immunosuppressed subjects, as well as those suffering from hemolytic anemia must also be considered "at risk" for aplastic crisis due to B19 infection.     

Primary Sjögren syndrome complicated by autoimmune hemolytic anemia and pure red cell aplasia

Patients with primary Sj?gren syndrome frequently present hematologic abnormalities, consisting mainly of immune cytopenias. Pure red cell aplasia is a very rare complication of primary Sj?gren syndrome. This is the first report in the literature describing the development of pure red cell aplasia combined with autoimmune hemolytic anemia in a 74-year-old woman with primary Sj?gren syndrome. In our patient, despite administration of diverse therapeutic schemes, such as corticosteroids, immunomodulating agents (intravenous immune globulin), immunosuppressive drugs (cyclophosphamide), and novel treatment options (monoclonal antibody directed against the CD20 antigen), no response was achieved. The present case suggests that the possibility of comorbid connective tissue disease should be a diagnostic consideration in patients with acquired pure red cell aplasia and autoimmune hemolytic anemia. Although most of the hematologic abnormalities that occur in primary Sj?gren syndrome are not clinically significant, serious and difficult-to-treat hematologic complications may also occur.     

Severe aplastic anemia associated with human parvovirus B19 infection in a patient without underlying disease

 Human parvovirus B19 (B19 virus) infection is known to induce aplastic crisis in patients with hemolytic anemia. In healthy subjects, B19 infection may sometimes cause mild pancytopenia, but these changes are transient and recovery is spontaneous. We report the first case of aplastic anemia in a previously healthy boy without any underlying diseases, following asymptomatic infection with the B19 virus. Laboratory examination initially showed thrombocytopenia, mild leukopenia in the peripheral blood, and severe hypoplastic bone marrow. Since pancytopenia developed and worsened progressively, immunosuppressive therapy was given, resulting in a complete remission. Despite the lack of an infectious prodrome, serological and histological analysis revealed an underlying infection with the B19 virus. Thus, B19 virus infection must be considered one of the causes of aplastic anemia in patients without underlying hemolytic anemia and an apparent episode of the viral infection. Received: August 28, 1998 / Accepted: November 18, 1998     

Remission of severe aplastic anemia associated with hepatitis B virus infection after viral clearance: potential role of lamivudine

Although viral hepatitis infection is known to be associated with aplastic anemia, a causal link between viral hepatitis and aplastic anemia has not been convincingly demonstrated. A case of hepatitis B-associated severe aplastic anemia is described which only partially responded to conventional immunosuppressive treatment but went into complete clinical remission after clearance of the hepatitis B virus. Disappearance of the hepatitis B virus occurred during lamivudine treatment and coincided with immune activation secondary to discontinuation of immunosuppressive therapy. This case was somewhat atypical in that a history of acute hepatitis preceding the aplastic anemia was absent. The observation made in this case report supports a cause-effect relationship between hepatitis B virus infection and aplastic anemia.     

Pure red cell aplasia associated with autoimmune hepatitis successfully treated with cyclosporine A

A 47-year-old female with a 17-year history of autoimmune hepatitis had been treated with prednisolone, azathioprine, and ursodeoxycholic acid. Although her alanine aminotransferase level occasionally showed mild abnormality, the prednisolone dose could not be increased because she had developed cataract during the course of her illness. In May 2012, she developed severe normochromic normocytic anemia without hemorrhage, and azathioprine was discontinued because it was suspected of being the cause. However, anemia recurred frequently even after discontinuation, necessitating repeated blood transfusions. Bone marrow analysis revealed selective erythroblastopenia, thus leading to a diagnosis of pure red cell aplasia. Cyclosporine A was administered, which led to a dramatic recovery from anemia, and stabilized her alanine aminotransferase levels. Furthermore, the prednisolone dose could be gradually tapered. Pure red cell aplasia associated with autoimmune hepatitis is extremely rare. The present case shows that patients with autoimmune hepatitis refractory to the standard treatment regimen and those with concomitant pure red cell aplasia may be treated with cyclosporine A.     

Carbamazepine-Induced Hemolytic and Aplastic Crises Associated with Reduced Glutathione Peroxidase Activity of Erythrocytes

Although pure red cell aplasia is a well-known side effect of carbamazepine treatment, intravascular hemolytic anemia is rare. We describe a 5-year-old boy who developed concurrent intravascular hemolytic anemia and erythroblastopenia, probably due to carbamazepine. Carbamazepine treatment was subsequently discontinued, and the patient was treated with red blood cell transfusions, haptoglobin, and methylprednisolone. His hematologic abnormalities were almost fully recovered within 2 weeks. Examination of the patient's and mother's erythrocyte enzyme activities revealed mildly decreased erythrocyte glutathione peroxidase (GSH-Px) activity. We speculate that patients with reduced GSH-Px activity are at a high risk of developing carbamazepine-induced hemolytic crisis and/or aplastic crisis.     

Successful Treatment with Cyclosporine and High-Dose Gamma Immunoglobulin for Persistent Parvovirus b19 Infection in a Patient with Refractory Autoimmune Hemolytic Anemia

We describe a patient with persistent pure red cell aplasia due to human parvovirus B19 (HPVB19) infection during immunosuppressive therapy for refractory autoimmune hemolytic anemia (AIHA). The patient had been given corticosteroid (CS) and/or azathioprine for AIHA. During the course of treatment, reticulocyte count and hemoglobin levels decreased suddenly. Bone marrow aspirate showed erythroid lineage-specific aplasia with a few giant proerythroblasts, suggesting the presence of HPVB19 infection. The diagnosis of aplastic crisis due to HPVB19 infection was based on positive test results by polymerase chain reaction for HPVB19 immunoglobulin M (IgM) antibody and B19 DNA. Although splenectomy followed by administration of high-dose gamma globulin (HDIG) and plasma exchange were performed, the crisis and hemolysis recurred. Aplastic crises occurred several times when the B19 IgG result became negative and the CD4+ lymphocyte count was less than 300/microL. The patient showed complete recovery from anemia after CS was switched to cyclosporin A (CsA) and intermittent administration of HDIG. The result for B19 IgG antibody was continuously positive, and the DNA result became negative after these treatments. The results in this case indicated that concomitant administration of CsA and intermittent administration of HDIG can lead to cure of chronic anemia due to HPVB19 infection in patients with refractory AIHA.     

Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation

Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed.     

Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians

Chronic hepatitis C virus (HCV) viremia has been known to provoke a plethora of autoimmune syndromes referred to as extrahepatic manifestations of chronic HCV infection. Aim of the current study was to assess the prevalence of rheumatologic manifestations among Egyptians with hepatitis C infection and its’ association with cryoglobulin profile. The current research represents a cross-sectional study where patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute over a period of 1 year were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antibody positive patients were all excluded from the research. Laboratory investigations as well as serological assay including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Three hundred and six patients having chronic HCV infection were interviewed in this research. The overall estimated prevalence of rheumatologic manifestations in the current research was 16.39%, chronic fatigue syndrome 9.5%, sicca symptoms 8.8%, arthralgia 6.5%, fibromyalgia 1.9%, myalgia 1.3%, arthritis 0.7%, cryoglobulinemic vasculitis 0.7%, autoimmune hemolytic anemia 0.7%, thrombocytopenia 0.7%. Xerophthalmia was significantly present in male population (p = 0.04), whereas fibromyalgia, cryoglobulinemic vasculitis, arthritis, and autoimmune hemolytic anemia were significantly present in female population under study (p < 0.05). In chronic HCV genotype 4 infection, the prevalence of rheumatologic manifestations was 16.3% with chronic fatigue syndrome and sicca sysmptoms being the most common with no significant correlation to the degree of elevation of liver disease or viral load.     

Pure red blood cell aplasia complicating chronic lymphatic leukemia

While the occurrence of autoimmune disorders such as hemolytic anemia and thrombocytopenia in chronic lymphatic leukemia (CLL) is well recognized, pure red blood cell aplasia (PRCA) complicating CLL is uncommon and intriguing. This is a report of the clinical course of a patient with B cell CLL who developed PRCA unresponsive to immunosuppressive therapy responsive to subsequent treatment with oxymethalone resulting in complete remission of PRCA.     

应用流式细胞仪检测自身免疫性溶血性贫血的临床观察

目的：提高自身免疫性溶血性贫血(AIHA)的诊断率。方法：对正常人及AIHA患者的红细胞经单克隆抗体标记后，采用Coulter Elite流式细胞仪技术测定并观察红细胞膜表面标记不同免疫物成分的百分数。结果：正常人少数红细胞膜表面附有免疫物；直接抗人球蛋白试验(Coombs试验)阳性的AIHA患者，其阳性凝集反应程度与红细胞膜表面标记免疫物的百分数呈正比例关系；Coombs试验阴性的AIHA患者，其红细胞膜表面标记免疫物百分数明显低于Coombs试验阳性者，但高于正常人；Coombs试验阴性而怀疑为AIHA患者，其红细胞膜表面标记免疫物的百分数有很大的差异。结论：采用流式细胞仪技术测定红细胞膜表面标记不同免疫成分百分数，灵敏度高，特异性强，可明显提高AIHA的诊断率和鉴别率。     

Definition and management of anemia in patients infected with hepatitis C virus.

Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C.     

Aplastic crisis due to human B19 parvovirus infection in red cell pyrimidine-5'-nucleotidase deficiency

Two siblings with chronic hemolytic anemia due to red cell pyrimidine-5'-nucleotidase (P-5'-N) deficiency, presented within a few days of each other with a febrile illness and pancytopenia. The cause of the aplastic crisis was an acute infection with human B19 parvovirus (B19 HPV) as proven by immunoelectron microscopy and DNA hybridization. This is the first report on the association of B19-HPV-related aplastic crisis with P-5'-N deficiency.     

HEPATITIS-ASSOCIATED APLASTIC ANEMIA AND ACUTE PARVOVIRUS B19 INFECTION: A REPORT OF TWO CASES AND A REVIEW OF THE LITERATURE

Hepatitis-associated aplastic anemia is rare in general, but occurs in up to 28% of patients receiving liver transplantation for fulminant non-A, non-B hepatitis. Cases are commonly young men with mild hepatitis but severe aplastic anemia. Although cases have been reported in association with hepatitis A, B, and C, most appear to be due to a non-A-B-C virus. We report two cases of acute hepatitis subsequently complicated by marrow hypoplasia in patients with acute parvovirus B19 infection. Hepatic manifestations of parvovirus B19 infection range from liver chemistry abnormalities to fulminant hepatic failure and aplastic anemia. Our cases demonstrate a less severe form of hepatitis-associated aplastic anemia, and together with other data, suggest that parvovirus B19 is at least one cause of hepatitis-associated aplastic anemia, and may be a heretofore underrecognized hepatotrophic virus.