Literature Scan
New and noteworthy research from the
medical literature landscape
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, crosssectional study of suspected TTP
cases reported in the United Kingdom (UK) TTP Registry between
January 2009 and December 2013.
This registry collects all cases of
TTP, and data are also gathered via
TABLE 1.
• Secondary TMA (25.57%)
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 antiADAMTS13 immunoglobulin G
antibodies). The remaining 460 nonTTP cases were classified as:
• 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 coauthors 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.”
• No diagnosis (33.91%)
• aHUS (27.17%)
Laboratory Parameters by Patient Group
Median ADAMTS13, percent (range)
Median platelet count
(range)
Median creatinine level,
lmol/L (range)
TTP
aHUS
STEC-HUS
Secondary TMA
5 (0–11)
66.5 (12–119)
56 (11–8 2)
15 x 109/L (0–96)
57 x 109/L (13–145)
35 x 109/L (14–106)
N/A
92 (43–374)
255 (23–941)
324 (117–639)
N/A
65 (12–130)
STEC-HUS = Shiga-like toxin-producing E. coli hemolytic uremic syndrome
TPE and Clinical Outcomes of Patients with ADAMTS13 Activity
≤10% Versus >10%
TABLE 2.
Received TPE
Number of TPE treatments
Plasma transfused, units
Hospital length of stay, days
Days to normal platelet count
ASH Clinical News
ADAMTS13 >10%
p Value
65 (95.6)
71 (38.2)
<0.0001
11 (5–19)
5 (3–7)
<0.0001
125 (46–233)
62 (39–86)
<0.0001
9 (7–17)
14 (8–27)
<0.002
4 (4–6)
6 (4–9)
0.01
Alive at 90 days
60 (95.2)
96 (57.1)
<0.0001
Alive at 360 days
53 (93.0)
76 (47.5)
<0.0001
1,384 (513–2,293)
126 (13–1,044)
<0.0001
Overall survival, days
40
ADAMTS13 ≤10%
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).
“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,
February 2016