Microangiopathic Haemolytic Anaemia: The Possible Role of Vascular Lesions in Pathogenesis

Brain, M. C.; Dacie, J. V.; Hourihane, D. O’B.

doi:10.1111/j.1365-2141.1962.tb06541.x

Cited by 497 publications

(170 citation statements)

References 18 publications

(8 reference statements)

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“…Classical HUS presents typically a few days after the onset of an acute diarrheal "prodromal" illness which is often bloody and shows remarkable similarities clinicopathologically (156) and radiologically (5,88,159,170) (86), the prodrome is nondiarrheal and may consist of upper or lower respiratory tract symptoms, fever, and vomiting. The other much less common types of HUS include a childhood form that is inherited (75) and adult forms that occur in association with pregnancy (29,172), oral contraceptive use (13,87), malignant hypertension (11,105), and various chronic illnesses (42,51).…”

Section: Hemorrhagic Colitismentioning

confidence: 99%

Infection by verocytotoxin-producing Escherichia coli

1989

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Verocytotoxin (VT)-producing Escherichia coli (VTEC) are a newly recognized group of enteric pathogens which are increasingly being recognized as common causes of diarrhea in some geographic settings. Outbreak studies indicate that most patients with VTEC infection develop mild uncomplicated diarrhea. However, a significant risk of two serious and potentially life-threatening complications, hemorrhagic colitis and the hemolytic uremic syndrome, makes VTEC infection a public health problem of serious concern. The main reservoirs of VTEC appear to be the intestinal tracts of animals, and foods of animal (especially bovine) origin are probably the principal sources for human infection. The term VT refers to a family of subunit exotoxins with high biological activity. Individual VTEC strains elaborate one or both of at least two serologically distinct, bacteriophage-mediated VTs (VT1 and VT2) which are closely related to Shiga toxin and are thus also referred to as Shiga-like toxins. The holotoxins bind to cells, via their B subunits, to a specific receptor which is probably the glycolipid, globotriosyl ceramide (Gb3). Binding is followed by internalization of the A subunit, which, after it is proteolytically nicked and reduced to the A1 fragment, inhibits protein synthesis in mammalian cells by inactivating 60S ribosomal subunits through selective structural modification of 28S ribosomal ribonucleic acid. The mechanism of VTEC diarrhea is still controversial, and the relative roles of locally acting VT and "attaching and effacing adherence" of VTEC to the mucosa have yet to be resolved. There is increasing evidence that hemolytic uremic syndrome and possibly hemorrhagic colitis result from the systemic action of VT on vascular endothelial cells. The role of antitoxic immunity in preventing the systemic complications of VTEC infection is being explored. Antibiotics appear to be contraindicated in the treatment of VTEC infection. The most common VTEC serotype associated with human disease is O157:H7, but over 50 different VT-positive O:H serotypes have now been identified. The best strategies for diagnosing human VTEC infection include testing for the presence of free VT in fecal filtrates and examining fecal cultures for VTEC by means of deoxyribonucleic acid probes that specify genes encoding VT1 and VT2. Both methods are currently confined to specialized laboratories and await commercial development for wider use. In the meantime, most laboratories should continue to screen for the most common human VTEC serotype, O157:H7, using a sorbitol-containing MacConkey medium.

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Section: Hemorrhagic Colitismentioning

confidence: 99%

Infection by verocytotoxin-producing Escherichia coli

1989

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“…Subsequently other ;authors (Dacie, Mollison, Richardson, Selwyn, and Shapiro, 1953;Allison, 1957;Aherne, 1957;Shumway and Miller, 1957;Lock and Dormandy, 1961) described similar cells and other bizarre types of poikilocyte in cases with renal failure of varied cause, but often in association wifh haemolytic anaemia and thrombocytopenia occurring in childhood. Brain, Dacie, and Hourihane (1962) have suggested that the common pathogenesis is not uraemia per se, but disease in small blood vessels, and have suggested the term 'micro-angiopathic haemolytic anaemia' for the condition. The abnormal red cells described by Brain et al included red cell fragments and various contracted and distorted microcytes of which triangular and helmet-shaped forms were common, plus crenated cells.…”

Section: Discussionmentioning

confidence: 99%

A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

Becroft¹,

Costello²,

Scott³

1965

Archives of Disease in Childhood

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“…It was reported as early as 1962 that HUS occurs associated with widespread metastatic cancer in patients not receiving chemotherapy (Brain et al, 1962). In 1980, the first report of a clinical condition best referred to as HUS in patients treated with mytomycin-C was published (Gulati et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Elevated reticulocyte count – a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report

et al. 1999

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The haemolytic-uraemic syndrome (HUS) is the consequence of one single pathogenic process, leading to either thromboticthrombocytopenic purpura (TTP), or to microangiopathic haemolytic anemia (MAHA), or to adult HUS (Streiff and Bell, 1993). The aetiology remains unknown, but a number of predisposing conditions have been recognized. Cytotoxic drugs have been identified as playing a causative role in the development of HUS in cancer patients. Gemcitabine is a newly developed nucleoside analogue with high activity against pancreatic adenocarcinoma. The diagnosis of HUS was made in a patient treated with gemcitabine for metastatic papillary carcinoma for about 10 months. The initial clinical hint indicating the development of HUS in this patient, the sudden onset of anaemia and thrombocytopenia, was erroneously considered to be the result of myelotoxicity exerted by gemcitabine. The strongly elevated reticulocyte count alone, however, enabled a diagnosis of a hyperregenerative anaemia due to haemolysis, ruling out myelotoxicity as the cause of the cytopenia. CASE REPORTIn December 1994, the clinical diagnosis of a pancreatic carcinoma of the head of the pancreas was made in the 40-year-old male patient. He was operated on (Whipple-procedure), and the final diagnosis was that of a papillary carcinoma. No further therapy was administered. In August 1996, the patient was seen at an out-patient department, as an increase in CA 19-9 had been observed since June 1996. The first recorded elevated value of CA 19-9 was 5440 units l -1 (normal upper limit = 25 U l -1 ). Abdominal ultrasound evidenced two intrahepatic lesions (about 2 cm in diameter) not detected on an examination performed in May 1996. The diagnosis of metastatic papillary carcinoma was made, and the patient was offered an experimental therapy with gemcitabine. Treatment was given as typical weekly infusions over 30 min, with a dose of 1600 mg day -1 for 3 weeks, followed by 1 week without gemcitabine. The drug was well tolerated, and no toxicity was observed. In January 1997, the hepatic lesions had decreased to about 0.5 cm in diameter (by ultrasound), and CA 19-9 was within the normal range. In June 1997, with a total dose of 53 400 mg of gemcitabine, a first episode of thrombocytopenia, 72 000 µl -1 , was observed. Until this date, the platelet count had been between 175 000 µl -1 and 685 000 µl -1 , with a median of 478 000 µl -1 . At the same time, since August 1996 the LDH had increased from normal values to 507 U l -1 (upper normal limit of 240 U l -1 ). The creatinine, below 1.0 mg dl -1 until this date, increased to 1.3 mg dl -1 . The haemoglobin value, ranging from 10.5 g dl -1 to 14.7 g dl -1 since August 1996, decreased to 8.2 g dl -1 . Notably, at this time no evidence of progressive disease was present. Attributing the thrombocytopenia and the anaemia to myelotoxicity of gemcitabine, the therapy was discontinued. At the end of August 1997, with gemcitabine discontinued for 7 weeks, the laboratory values had worsened: Plt 101 000 µl -1 ; Hb 7.2...

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Microangiopathic Haemolytic Anaemia: The Possible Role of Vascular Lesions in Pathogenesis

Cited by 497 publications

References 18 publications

Infection by verocytotoxin-producing Escherichia coli

Infection by verocytotoxin-producing Escherichia coli

A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

Elevated reticulocyte count – a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report

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