Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group

Go, Ronald S.; Winters, Jeffrey L.; Leung, Nelson; Murray, David; Willrich, Maria Alice V.; Abraham, Roshini S.; Amer, Hatem; Hogan, William J.; Marshall, Ariela L.; Sethi, Sanjeev; Tran, Cheryl L.; Chen, Dong; Pruthi, Rajiv K.; Ashrani, Aneel A.; Fervenza, Fernando C.; Cramer, Carl H.; Rodriguez, Vilmarie; Wolanskyj, Alexandra P.; Thomé, Stephan D.; Hook, C. Christopher; Garovic, Vesna D.; Yui, Jennifer; Botero, Juliana Perez

doi:10.1016/j.mayocp.2016.05.015

Cited by 57 publications

(49 citation statements)

References 128 publications

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“…Retrospective aHUS case series (prior to the availability of eculizumab) reported improved haematological parameters with PE, but long‐term outcomes were often poor . Thus, we do not support a recent US guideline recommending PE for ‘complement‐mediated TMA’, with substitution of eculizumab only in patients ‘refractory to or dependent on’ PE …”

Section: Evidence For Treatment Of Ahusmentioning

confidence: 58%

“…The initial diagnosis of aHUS 9,25,[38][39][40] (or 'complementmediated TMA' 32 ) is currently based on exclusion of STEC-HUS and TTP, hence requiring confirmation of ADAMTS13 activity ≥10% (Fig. 1).…”

Section: Diagnosis Of Ahus Ahus As a Diagnosis Of Exclusionmentioning

confidence: 99%

“…28,29 Thus, we do not support a recent US guideline recommending PE for 'complement-mediated TMA', with substitution of eculizumab only in patients 'refractory to or dependent on' PE. 32…”

Section: Plasma Therapy In Ahusmentioning

confidence: 99%

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

Fox

Cohney

Kausman

et al. 2018

Internal Medicine Journal

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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.

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Section: Evidence For Treatment Of Ahusmentioning

confidence: 58%

Section: Diagnosis Of Ahus Ahus As a Diagnosis Of Exclusionmentioning

confidence: 99%

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

Fox

Cohney

Kausman

et al. 2018

Internal Medicine Journal

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“…The initial diagnosis of aHUS (or ‘complement‐mediated TMA’) is currently based on exclusion of STEC‐HUS and TTP, hence requiring confirmation of ADAMTS13 activity ≥10% (Fig. ).…”

Section: Diagnosis Of Ahusmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

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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“…The ADAMTS13 activity assay is increasingly being used to guide treatment decisions for patients with TMA . Many investigators have examined and confirmed the relationship between severe ADAMTS13 deficiency (activity levels of 10% or less) and a clinical diagnosis of TTP in patients with TMA .…”

mentioning

confidence: 99%

Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency

Bendapudi

Uhl

et al. 2017

Transfusion

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BACKGROUND The a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity assay has become important in distinguishing autoimmune thrombotic thrombocytopenic purpura from other forms of thrombotic microangiopathy (TMA). Although the significance of severe deficiency in ADAMTS13 (activity levels 10% or less) has been well defined, little data are available on the clinical importance of mild to moderate deficiency (activity levels 11%‐70%) among patients with TMA. STUDY DESIGN AND METHODS We conducted a retrospective study using the Harvard TMA Research Collaborative Registry. Among 254 patients who met the inclusion criteria for TMA, 186 patients with ADAMTS13 activity levels greater than 10% were divided into moderate‐deficiency (11%‐40%), mild‐deficiency (41%‐70%), and no‐deficiency (greater than 70%). RESULTS Compared with mild or no deficiency, moderate ADAMTS13 deficiency correlated with older age; higher bilirubin and international normalized ratio; and increased frequency of sepsis, shock, or multiorgan failure. Platelet counts, lactate dehydrogenase levels, and the presence of renal or neurologic dysfunction did not vary across the three patient cohorts. While moderate ADAMTS13 deficiency was associated with increased 90‐day mortality in univariate analysis, this association was no longer significant in multivariate analysis. Variables that independetly predicted 90‐day mortality in this cohort of patients included Charlson comorbidity index, alanine aminotransferase level, platelet count, creatinine, and the presence of sepsis, shock, or multiorgan failure. CONCLUSION Moderately deficient ADAMTS13 activity identifies a cohort of patients with TMA who are at increased risk for 90‐day mortality. The ADAMTS13 activity level in this group is not an independent predictor of poor outcomes but instead appears to be a marker of disease acuity.

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Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group

Cited by 57 publications

References 128 publications

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

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

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

Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency

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