Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand

Lucy C. Fox, Solomon J. Cohney, Joshua Y. Kausman, Jake Shortt, Peter D. Hughes, Erica M. Wood, Nicole M. Isbel, Theo de Malmanche, Anne Durkan, Pravin Hissaria, Piers Blombery, Thomas D. Barbour

Research output: Contribution to journalReview ArticleOtherpeer-review

Abstract

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4–8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Original languageEnglish
Pages (from-to)507-517
Number of pages11
JournalNephrology
Volume23
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • atypical haemolytic uraemic syndrome
  • plasma exchange
  • thrombotic thrombocytopenic purpura

Cite this

Fox, Lucy C. ; Cohney, Solomon J. ; Kausman, Joshua Y. ; Shortt, Jake ; Hughes, Peter D. ; Wood, Erica M. ; Isbel, Nicole M. ; de Malmanche, Theo ; Durkan, Anne ; Hissaria, Pravin ; Blombery, Piers ; Barbour, Thomas D. / Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand. In: Nephrology. 2018 ; Vol. 23, No. 6. pp. 507-517.
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abstract = "Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4–8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.",
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author = "Fox, {Lucy C.} and Cohney, {Solomon J.} and Kausman, {Joshua Y.} and Jake Shortt and Hughes, {Peter D.} and Wood, {Erica M.} and Isbel, {Nicole M.} and {de Malmanche}, Theo and Anne Durkan and Pravin Hissaria and Piers Blombery and Barbour, {Thomas D.}",
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Fox, LC, Cohney, SJ, Kausman, JY, Shortt, J, Hughes, PD, Wood, EM, Isbel, NM, de Malmanche, T, Durkan, A, Hissaria, P, Blombery, P & Barbour, TD 2018, 'Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand' Nephrology, vol. 23, no. 6, pp. 507-517. https://doi.org/10.1111/nep.13234

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand. / Fox, Lucy C.; Cohney, Solomon J.; Kausman, Joshua Y.; Shortt, Jake; Hughes, Peter D.; Wood, Erica M.; Isbel, Nicole M.; de Malmanche, Theo; Durkan, Anne; Hissaria, Pravin; Blombery, Piers; Barbour, Thomas D.

In: Nephrology, Vol. 23, No. 6, 01.06.2018, p. 507-517.

Research output: Contribution to journalReview ArticleOtherpeer-review

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