The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry

Abstract

SummaryThrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24Á57%) and haemolytic uraemic syndrome (HUS) (27Á17% aHUS, 2Á83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 9 10 9 /l; range 0-96) than aHUS (57 9 10 9 /l; range 13-145, P < 0Á0001) or STEC-HUS (35 9 10 9 /l; range 14-106, P < 0Á0001); they also had lower creatinine levels (92 lmol/l; range 43-374) than aHUS (255 lmol/l; range 23-941, P < 0Á0001) and STEC-HUS (324 lmol/l; range 117-639, P < 0Á0001). However, 12/34 (35Á3%) aHUS patients had a platelet count <30 9 10 9 /l and 26/150 (17Á3%) of TTP patients had a platelet count >30 9 10 9 /l; 23/ 150 (15Á3%) of TTP patients had a creatinine level >150 lmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.

Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score–matched study

“…Subsequently, a FRETS‐based assay utilizing the VWF73 substrate was used for all assays performed at both laboratories. Severe deficiency in ADAMTS13 was defined as an activity level of not more than 10% based on previous work indicating that this cutoff provides excellent sensitivity and specificity for idiopathic TTP …”

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

“…delirium, seizures). It has been suggested that more severe thrombocytopenia (platelet count <30 × 10 9 /L) and milder renal impairment (serum creatinine <200 μmol/L) may help to distinguish TTP from aHUS but these criteria are neither sensitive nor specific . Rather, TTP is defined by severely reduced (<10%) activity of the von Willebrand factor (vWF)‐cleaving protease, ADAMTS13.…”

How do we reduce plasma transfusion in Rhode Island?

“…TTP is a rare disorder with an incidence of four to 11 patients per 10 6 per year . In the past, many patients with thrombocytopenia and features of TMA were misdiagnosed with TTP, and some were subjected to a trial of TPE involving, by definition, large‐volume plasma transfusion. Clarification in 1998 that a sine que non for the diagnosis of TTP is severe deficiency of ADAMTS13 has allowed a more systematic approach to this situation.…”