Differential diagnosis of thrombotic microangiopathy in nephrology

T Sakari Jokiranta,Oğuz Soylemezoglu,Rosanna Coppo,Christoph Gasteyger,Michel Tsimaratos,Mohan Shenoy,Ondrej Viklicky,Tatiana Pankratenko,Saleh Al Shorafa,Manuel Macia,Hermann Haller,Jack Wetzels

doi:10.1186/s12882-017-0727-y

Abstract

BackgroundThe differential diagnosis of thrombotic microangiopathy (TMA) is complex however the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions. A survey was devised with the objective of understanding current practices across Europe and the Middle East, and of challenges when diagnosing the cause of TMA.MethodsOver 450 clinicians, from 16 countries were invited to complete an online survey.ResultsOf 254 respondents, the majority were nephrologists, had >10 years’ experience in their specialty, and had diagnosed a patient with TMA. The triad of thrombocytopenia, haemolytic anaemia and acute kidney injury are the main diagnostic criteria used. Responses indicate that a differential diagnosis of TMA is usually made within 1–2 (53%) or 3–4 days (26%) of presentation. Similarly, therapy is usually initiated within the first 4 days (74%), however 13% report treatment initiation >1-week post-presentation. Extrarenal symptoms and a panoply of other conditions are considered when assessing the differential diagnosis of TMA. While 70 and 78% of respondents stated they always request complement protein levels and ADAMTS13 activity, respectively. Diagnostic considerations of paediatric and adult nephrologists varied. A greater proportion of paediatric than adult nephrologists consider extrarenal manifestations clinically related to a diagnosis of TMA; pulmonary (45% vs. 18%), gastrointestinal (67% vs. 50%), CNS (96% vs. 84%) and cardiovascular (54% vs. 42%), respectively. Variability in the availability of guidelines and extent of family history taken was also evident.ConclusionsThis survey reveals the variability of current practices and the need for increased urgency among physicians in the differential diagnosis of TMA, despite their experience. Above all, the survey highlights the need for international clinical guidelines to provide systematically developed recommendations for understanding the relevance of complement protein levels, complement abnormalities and ADAMTS13 testing, in making a differential diagnosis of TMA. Such clinical guidelines would enable physicians to make a more rapid and informed diagnosis of TMA, therefore initiate effective treatment earlier, with a consequent improvement in patient outcomes.

Highlights

The differential diagnosis of thrombotic microangiopathy (TMA) is complex the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions
Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are the two most common clinical conditions characterised by TMA lesions but have differing aetiology, pathophysiology and management strategies [1]
The atypical form of HUS is a rare, life-threatening disease of chronic, uncontrolled complement activation that leads to TMA with severe organ damage

Summary

Introduction

The differential diagnosis of thrombotic microangiopathy (TMA) is complex the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are the two most common clinical conditions characterised by TMA lesions but have differing aetiology, pathophysiology and management strategies [1]. HUS is a clinical syndrome characterised by the obstruction of microvasculature (most commonly in the kidney) by plateletfibrin thrombi despite normal ADAMTS13 activity. The atypical form of HUS (aHUS) is a rare, life-threatening disease of chronic, uncontrolled complement activation that leads to TMA with severe organ damage. The rapid progression of TMA, associated with potentially irreversible damage to organs in patients with aHUS, indicates a need for urgent treatment. A recent report demonstrated a greater and more sustained recovery in renal function when eculizumab therapy is initiated within 7 days of aHUS onset [8]

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