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

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. Although 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 (a disintegrin and metalloprotease thrombospondin, number 13) activity. 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. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies 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.

Renal genetics in Australia: Kidney medicine in the genomic age

“…The risk of post‐transplant recurrence is especially high in patients with mutations in complement genes, with up to 90% risk if recurrence with those with a CFH mutation . Therefore, a genetic diagnosis will assist to inform the decision about when to use prophylactic complement inhibitors in this situation . Furthermore, with new treatments, such as tolvaptan emerging for autosomal dominant polycystic kidney disease, it may be necessary to have a precise molecular diagnosis, especially for those participating in therapeutic trials and those without a positive family history to demonstrate accurate results …”

Immune-mediated thrombotic thrombocytopenic purpura in patients with and without systemic lupus erythematosus: a retrospective study

“…A randomized clinical trial showed that corticosteroid pulse therapy may decrease mortality and increase the rate of complete remission among patients with clinically diagnosed TTP [ 18 ]. Many authors agree that for severe cases of TTP, steroid pulse therapy should be considered [ 19 , 20 ]. Considering the role of autoimmunity in both SLE-TTP and primary iTTP and the overlap of these two disease entities, primary iTTP may benefit from corticosteroid pulse therapy.…”

Trombotic Trombocytopenic Purpura Presenting With Headache And Agitation: Case Report

“…ADAMTS-13'ün düşük aktivitesi olan hastalarda, rituksimab kullanımı nüks riskini azaltabilir. [13][14][15] Sonuç TTP, sıklıkla nörolojik bulguları da olan multisistem bir hastalıktır. Tedaviye erken başlanması fatal olabilen hastalığın prognozunun olumlu seyretmesi açısından önemlidir.…”