Assessing ADAMTS13 Assays in Thrombotic Microangiopathies

Two registry-based studies recently published in the British Journal of Haemotology focused on the role of ADAMTS13 measurements in thrombotic microangiopathies (TMAs) in confirming a diagnosis of thrombocytopenic purpura (TTP) and predicting outcomes among TMA patients.

TMAs, which are characterized clinically by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, are associated with a variety of conditions or may be seen after exposure to certain medications. Measuring ADAMTS13 levels remains the main method of diagnosing TTP, though the availability of this test is limited and the rarity of TTP makes large registry-based analyses an important tool for studying this disease.

Sevda Hassan, from the Department of Nephrology at the Royal London Hospital, and colleagues conducted a retrospective, cross-sectional study of suspected TTP cases reported in the United Kingdom (UK) TTP Registry between January 2009 and December 2013.1 This registry collects all cases of TTP, and data are also gathered via referrals for ADAMTS13 testing in patients with a presumed diagnosis of acute hemolytic-uremic syndrome (aHUS), another TMA.

“Despite advances in our understanding of [TMAs], differentiating between them clinically can be challenging, and frequently other more common TMAs need to be excluded,” Dr. Hassan and colleagues wrote. “Lack of rapid diagnostic methods and the need to instigate treatment early has resulted in a reliance on clinical criteria alone, pending a conclusive diagnosis.”

With this study, the researchers explored how ADAMTS13 levels may help differentiate these cases, and determined which clinical parameters could be useful in distinguishing among TMAs.

Of 810 cases included in the study, 350 were confirmed as TTP (defined as an ADAMTS13 activity <10% and/or the presence of anti-ADAMTS13 immunoglobulin G antibodies). The remaining 460 non-TTP cases were classified as:

  • No diagnosis (33.91%)
  • aHUS (27.17%)
  • Secondary TMA (25.57%)
  • Shiga-like toxin-producing E. coli (2.83%)
  • TMA other (6.74%)
  • Non-TMA (4.78%)

ADAMTS13 levels were significantly lower in patients with TTP (median = 5%; range = 0-11) compared with patients with confirmed diagnoses of aHUS or HUS (median = 66.5%; range = 12-119; p<0.0001; TABLE 1). Patients with TTP also had significantly lower median platelet counts (15 x 109/L vs. 57 x 109/L for aHUS and vs. 35 x 109/L; p<0.0001 for both) and lower median creatinine levels (92 lmol/L vs. 255 lmol/L for aHUS vs. 324 lmol/L for HUS; p<0.0001 for both).

However, Dr. Hassan and co-authors noted, “clinical parameters alone were not felt to sufficiently rule out a TTP diagnosis. … Indeed, for approximately a fifth of all TTP cases, using routine laboratory parameters would have failed to identify the correct diagnosis, which could have an impact on therapy.”

A noted limitation of the study was that the UK TTP Registry only provides datasets on TTP cases; the non-TTP cases, therefore, did not have data available on blood counts and final diagnoses.

“ADAMTS13 assays are useful to differentiate TTP from other associated TMAs,” the authors concluded. “Prompt identification, treatment, and referral are essential and highlight the importance of using a number of methods, including ADAMTS13 assays, to confirm the diagnosis.”

In the second study, Pavan K. Bendapudi, MD, from the Division of Hematology at Massachusetts General Hospital and Harvard Medical School, and colleagues analyzed data from the Harvard TMA Research Collaborative, a multi-institutional registry, to examine the positive and negative predictive values of ADAMTS13 assay in outcomes in patients with TTP treated with therapeutic plasma exchange (TPE).2

“Our data show that patients with severe ADAMTS13 deficiency represent [a] clinically distinct cohort that responds well to TPE,” Dr. Bendapudi and colleagues reported. “In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.”

The researchers analyzed data from 254 consecutive patients admitted with suspected TTP to three academic medical centers in Boston between January 8, 2004, and August 6, 2013.

Patients were eligible for study inclusion if they were admitted with thrombocytopenia and schistocytes indicative of MAHA for whom an ADAMTS13 assay was sent.

A total of 186 patients had an ADAMTS13 activity level >10 percent, with a median ADAMTS13 activity level of 56 percent (range = 42-68). Patients with severe ADAMTS13 deficiency were more likely to be younger and female than those with other TMAs, Dr. Bendapudi and colleagues reported.

Length of hospitalization periods, time to platelet count recovery, and overall survival were all improved among patients with severe ADAMTS13 deficiency compared with patients without this deficiency (TABLE 2).

Nearly all patients with severe ADAMTS13 deficiency received therapeutic plasma exchange (TPE), compared with those without severe deficiency (95.6% vs. 38.2%, respectively; p<0.0001). Use of TPE in patients with ADAMTS13 activity >10 percent, however, varied significantly across the institutions included in the study (range = 13.2-63.8%; p<0.0001).

However, this variation in the use of TPE in TMA patients without severe ADAMTS13 deficiency was not associated with a difference in mortality (60% in patients with ADAMTS13 ≤10% and 96% for patients with ADAMTS13 >10%; p=0.98).

There are a number of limitations inherent to this study, given the nature of the retrospective review, Dr. Benapudi and co-authors noted. “For example, we were not able to reliably document TTP relapses that may have been treated at institutions outside of the consortium. … Also, suspected cases of TTP for which an ADAMTS13 assay was not sent would not have been captured in the dataset.”

“Our work underscores the need for a clinical scoring tool to assist in the rapid identification of patients with severe ADAMTS13 deficiency so that these cases can quickly move on to receive life-saving care,” the authors concluded.


  1. Hassan S, Westwood J, Ellis D, et al. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry. Br J Haematol. 2015 September 11. [Epub ahead of print]
  2. Bendapudi PK, Li A, Hamdan A, et al. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. Br J Haematol. 2015 August 28. [Epub ahead of print]

TABLE 1. Laboratory Parameters by Patient Group
Median ADAMTS13, percent (range) 5 (0–11) 66.5 (12–119) 56 (11–82) 65 (12–130)


Median platelet count (range) 15 x 109/L (0–96) 57 x 109/L (13–145) 35 x 109/L (14–106) N/A
Median creatinine level, lmol/L (range) 92 (43–374) 255 (23–941) 324 (117–639) N/A
STEC-HUS = Shiga-like toxin-producing E. coli hemolytic uremic syndrome

TABLE 2. TPE and Clinical Outcomes of Patients with ADAMTS13 Activity ≤10% Versus >10%
ADAMTS13 ≤10%


ADAMTS13 >10% p Value
Received TPE 65 (95.6) 71 (38.2)




Number of TPE treatments 11 (5–19)


5 (3–7)




Plasma transfused, units


125 (46–233)


62 (39–86)




Hospital length of stay, days


9 (7–17)


14 (8–27)


Days to normal platelet count


4 (4–6)


6 (4–9) 0.01


Alive at 90 days


60 (95.2)


96 (57.1)




Alive at 360 days 53 (93.0)


76 (47.5)




Overall survival, days 1,384 (513–2,293)


126 (13–1,044) <0.0001