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. 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.

Renal genetics in Australia: Kidney medicine in the genomic age

“…37,38 Therefore, a genetic diagnosis will assist to inform the decision about when to use prophylactic complement inhibitors in this situation. 39 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. 40 A definitive diagnosis may negate the need for prolonged diagnostic investigations and surveillance in addition to guiding management.…”

Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Narrative Review of Diagnosis and Treatment in Adults

“…52 There is no recommended standard regimen; some more common dosing examples include oral prednisolone 1 mg/kg/d, or for severe cases, pulse intravenous (IV) methylprednisolone 1 g daily for the first 3 days. 43 We use steroids during the initial phase of treatment for all iTTP patients, typically oral prednisolone at the above dose and we commence weaning when the patient has successfully ceased PEX, and ADAMTS13 activity is above 20%. Pulse IV methylprednisolone is used in patients with high-risk features or neurological sequelae which prohibit oral intake.…”

“…Nevertheless, the role of bortezomib remains uncertain and prospective studies are necessary to evaluate the efficacy of bortezomib in iTTP. 43 Recombinant ADAMTS13 is currently under investigation for the treatment of patients with cTTP. 80 In the setting of iTTP, supratherapeutic concentrations of rADAMTS13 may be able to saturate anti-ADAMTS13 autoantibodies in iTTP and increase ADAMTS13 activity.…”

Development and validation of a prediction model (AHC) for early identification of refractory thrombotic thrombocytopenic purpura using nationally representative data

“…[1][2][3][4] It is characterized by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and multiple end organ dysfunction. 3,[5][6][7][8][9] The underlying pathophysiology of iTTP is a severe ADAMTS13 deficiency due to inhibitory autoantibodies against ADAMTS13. [9][10][11] Immune-mediated thrombotic thrombocytopenic purpura is an acute haematological emergency and is associated with substantial mortality, requiring prompt diagnosis and treatment.…”

“…Current standard therapy consists of therapeutic plasma exchange (TPE) and corticosteroids. 5,9,[12][13][14] Since the adoption of TPE, the mortality of iTTP has decreased substantially from 90% to 20%. 13,15,16 Although TPE together with corticosteroids achieve successful outcomes, approximately 10-42% of TTP patients remain refractory to the therapy and are associated with poor outcomes.…”