Severe Aplastic Anaemia following Hepatitis A

Doménech, Pedro; Palomeque, A.; Martínez-Gutiérrez, A; Viñolas, Núria; Vela, Enrique; Jimenez, R. Malfeito

doi:10.1159/000206061

Cited by 28 publications

(13 citation statements)

References 11 publications

(18 reference statements)

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“…Hemolysis may be autoimmune in nature, associated with antibodies to triosephosphate isomerase (208,209), and can be severe (156,244). Other hematologic abnormalities include aplastic anemia (73), autoimmune thrombocytopenic purpura (47), and pure red cell aplasia (221).…”

Section: Extrahepatic Manifestationsmentioning

confidence: 99%

Hepatitis A: Old and New

2001

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The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated

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Section: Extrahepatic Manifestationsmentioning

confidence: 99%

Hepatitis A: Old and New

2001

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“…Additionally, rare fatal courses of AA with serological evidence of HAV being the responsible agent have been reported (7). Previous data addressing the influence of HAV on in vitro hematopoiesis demonstrated virus-induced suppression of the myelomonocytic lineage as well as infection of a subpopulation of stromal cells that were morphologically characterized as fibroblasts and/or MAC (4,17).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, increased MO numbers in the nonadherent fraction of HAV-challenged LTBMCs are indicative of the disturbance of MO adherence. These findings suggest that HAV infection leads to a disorder of the mononuclear phagocytic system which may contribute to functional abnormalities of the bone marrow stroma.Infections with hepatitis A virus (HAV) are associated with perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of aplastic anemia (AA) (5,7,9). The clinical syndrome of AA, which may also be caused by exposure to drugs, radiation, chemicals, or other hepatotropic viruses, is characterized by bone marrow hypocellularity and peripheral blood pancytopenia.…”

mentioning

confidence: 99%

“…Infections with hepatitis A virus (HAV) are associated with perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of aplastic anemia (AA) (5,7,9). The clinical syndrome of AA, which may also be caused by exposure to drugs, radiation, chemicals, or other hepatotropic viruses, is characterized by bone marrow hypocellularity and peripheral blood pancytopenia.…”

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confidence: 99%

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Hepatitis A Virus Suppresses Monocyte-to-Macrophage Maturation In Vitro

Wünschmann

Becker

Vallbracht

2002

J Virol

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To analyze the pathogenetic mechanism of hematopoietic dysregulation associated with hepatitis A virus (HAV) infections, we studied the influence of HAV on monocyte (MO)-to-macrophage (MAC) maturation in vitro. Exposure of peripheral blood-derived mononuclear cells (MNC) to HAV led to diminished adherence of MO to plastic. Furthermore, HAV inhibited the ability of peripheral blood MO to differentiate toward MAC. Freshly isolated and 14-day-old MO cultures demonstrated reduced differentiation and decreased phagocytic capacity after challenge with HAV. Viral replication in MO/MAC cultures was confirmed by titration of infectious virus. We also determined the influence of HAV on the MO/MAC population in human long-term bone marrow cultures (LTBMCs). Inoculation of bone marrow MNC with HAV suppressed the establishment of an adherent stromal layer containing a reduced number of MAC. Furthermore, increased MO numbers in the nonadherent fraction of HAV-challenged LTBMCs are indicative of the disturbance of MO adherence. These findings suggest that HAV infection leads to a disorder of the mononuclear phagocytic system which may contribute to functional abnormalities of the bone marrow stroma.Infections with hepatitis A virus (HAV) are associated with perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of aplastic anemia (AA) (5,7,9). The clinical syndrome of AA, which may also be caused by exposure to drugs, radiation, chemicals, or other hepatotropic viruses, is characterized by bone marrow hypocellularity and peripheral blood pancytopenia. The pathogenesis of AA associated with viral hepatitis is not well understood, although a variety of hematopoietic and immunoregulatory defects have been described, including direct infection of bone marrow progenitor cells and impairment of stromal function (6,11,14).The bone marrow stroma represents a heterogeneous cell pool, consisting of fibroblasts, endothelial cells, adipocytes, and macrophages (MAC). Growth and differentiation of the hematopoietic cell population is dependent on its close association with stromal cells, which produce regulatory cytokines necessary to control hematopoiesis. In previous studies with human long-term bone marrow cultures (LTBMCs), HAVinduced inhibition of hematopoiesis was demonstrated by granulocyte-macrophage colony formation assays, and sequential determination of virus titers in the supernatant provided evidence for HAV replication in LTBMCs (3, 4, 17). However, our knowledge about which cell types of the heterogeneous stromal cell population are permissive for HAV is limited. Whereas the HAV infection of fibroblasts is well characterized (16), very little is known about the interaction of HAV with MAC, endothelial cells, or adipocytes. In this study, we focused on the interaction of HAV with peripheral blood monocytes (MO) and MAC, using primary cultures of MO and LTBMCs. MATERIALS AND METHODS Virus.The virus used in this study was HAV strain GBM adapted to human fibroblasts.Cell isolation. Mononuc...

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“…However, hepatitis A rarely causes pancytopenia except in the recovery phase of the disease. 20 Ehrlichiosis has been found with increasing frequency in the northeastern United States. It is transmitted by ticks, and up to 20% of patients are unaware of a tick bite.…”

mentioning

confidence: 99%