American Journal of Therapeutics 19, e53–e55 (2012)

Acquired Thrombotic Thrombocytopenic Purpura

Associated With Reversible Severe Renal Failure
Requiring Hemodialysis

Aakanksha Prasad, MD, MPH,1* Dhaval Shah, MD,1

Amit Asija, MD,1 and John Nelson, MD1,2

Thrombotic thrombocytopenic purpura (TTP) is an uncommon hematologic disorder characterized

by microangiopathic hemolytic anemia (MHA) and thrombocytopenia with or without fever, renal
failure, and neurologic manifestations. Although the full pentad was required for the diagnosis of
TTP until recently, because of the high mortality of untreated TTP and the varying manifestations
of the disease itself, diagnostic criteria for TTP have been relaxed since the emergence of plasma
exchange as effective treatment for TTP. The occurrence of MHA and thrombocytopenia without an
alternate cause is now sufficient to initiate therapy. Renal dysfunction in acquired TTP, when it
occurs, is transient and responds to therapeutic plasma exchange readily. Here we report a patient
with acquired TTP who had no preexisting renal pathology but developed severe prolonged renal
failure requiring multiple rounds of hemodialysis with eventual complete recovery of renal
function. We adopted an intensive approach including steroids, rituximab, cyclosporine, twice
daily plasma exchange, and hemodialysis. We believe that this was responsible for complete
recovery of the patient. However, the reason for this unusually severe renal manifestation needs
further study.

Keywords: thrombotic thrombocytopenic purpura, renal failure

CASE indirect hyperbilirubinemia [total bilirubin (TB) =

A 52-year-old woman presented with acute onset of
nausea, vomiting, headache, abdominal pain, bloody
diarrhea, and skin rash to a local hospital. On
admission, laboratory examination was significant for
anemia (Hgb/Hct = 6.3/17.3), severe thrombocytopenia
(platelets = 15,000/mm3), high white count (15,800/
mm3), high BUN and creatinine (Cr) (87/8.3 mg/dL),
1
Department of Medicine; and 2Division of Hematology-Oncology,
New York Medical College, Valhalla, NY.
No conflict of interest exists for any of the authors.
There is no source of funding.
*Address for correspondence: 95 Grasslands Rd, PMB # 493,
Valhalla, NY 10595. E-mail: draakanksha@gmail.com
1075–2765 Ó 2012 Lippincott Williams & Wilkins
2.2 mg/dL, direct bilirubin (DB) = 0.6 mg/dL], high
lactate dehydrogenase (LDH) (914 U/L), and normal
coagulation profile (Table 1). Peripheral smear showed
.5 schistocytes/high power field. The direct Coombs
and urine pregnancy test were both negative. The
patient was diagnosed with thrombotic thrombocyto-
penic purpura (TTP)/ hemolytic uremic syndrome
(HUS) and started on daily plasma exchange. Platelet
count initially improved reaching up to 78,000/mm3
but subsequently decreased to 19,000/mm3. Due to
persistent oliguric renal failure, patient received
hemodialysis 3 times before being transferred to our
hospital.
On admission to our hospital, patient had a hemat-
ocrit of 25.8%, platelet count of 19,000/mm3, and
persistent oliguric renal failure (BUN/Cr = 48/8.1
mg/dL, urine output = 160 cc/24 hours; Table 1).
Peripheral smear showed 2–3 schistocytes per
www.americantherapeutics.com
 e54 Prasad et al

high-power field. Antinuclear antibody titers were

Platelets: 1,70,000/mm3

Hgb, hemoglobin; Hct, hematocrit; WBC, white blood cell; BUN, blood urea nitrogen; Cr, creatinine; LDH, lactate dehydrogenase; TB, total bilirubin; CBC, complete blood
negative, C3 and C4 levels were normal. Patient was

Day of discharge

WBC: 11,800/mm3
started on twice daily 1 plasma volume exchanges,

from WMC

BUN: 21 mg/dL
using cryoprecipitate depleted plasma and oral pred-

DB: 0.1 mg/dL

TB: 0.3 mg/dL
Cr: 0.9 mg/dL
Hgb: 8.5 g/dL

LDH: 201 U/L

nisone 100 mg daily. Two days later, patient had

Hct: 25.5%
transient slurring of speech. A disintegrin and
metalloproteinase with a thrombospondin type 1
motif, member 13 (ADAMTS-13) was absent in
the plasma and inhibitor level was greater than 8.
This high inhibitor level in the appropriate clinical
setting confirmed the diagnosis of thrombocytopenic
Reticulocyte count: 6.4
Platelets: 15,000/mm3

purpura (TTP). In spite of therapy with prednisone,

Day 5 at WCMC

platelet count did not rise and rituximab and cyclo-

WBC: 13,700/mm3
(cyclosporine
was added)

Haptoglobin , 8
BUN: 56 mg/dL

sporine were added on days 3 and 5 of admission,

DB: 1.2 mg/dL
TB: 3.1 mg/dL
Cr: 6.4 mg/dL
LDH: 933 U/L
respectively. After 2 weeks of twice daily plasma
Hgb: 8 g/dL
Hct: 23.9%

exchange, prednisone, cyclosporine, rituximab, and

hemodialysis, platelet count started improving. She
received a total of 22 treatments of plasma exchange
and 4 cycles of hemodialysis at our hospital. Urine
output gradually increased with decrease in creatinine
levels and no further need for hemodialysis. Before
Reticulocyte count: 5
Platelets: 9,000/mm3

discharge, repeat ADAMTS-13 level was 54 and her

Day 3 at WCMC

WBC: 15,200/mm3

prednisone was slowly tapered. Five months after

Haptoglobin , 8
was added)
(rituximab

BUN: 61 mg/dL

LDH: 1026 U/L

DB: 0.9 mg/dL

this episode, the patient remains asymptomatic with

TB: 2.4 mg/dL
Cr: 8.2 mg/dL
Hgb: 6.9 g/dL

no residual impairment in renal function (creatinine =

Hct: 20.6%

0.69 mg/dL).

DISCUSSION
Patients with hereditary TTP may go on to develop
chronic renal failure.1 In contrast, renal involvement
Reticulocyte count: 4.2
Platelets: 19,000/mm3

in acquired TTP is mild and results in a transient

On admission

WBC: 13,600/mm3

Haptoglobin , 10

elevation in serum creatinine. There have been only

at WMC

BUN: 48 mg/dL

a few cases of acquired thrombotic microangiopathy

DB: 0.8 mg/dL
TB: 2.1 mg/dL
Cr: 8.1 mg/dL
Hgb: 8.8 g/dL

LDH: 785 U/L

with renal involvement severe enough to require

Hct: 25.8%

hemodialysis. These have been reported primarily in

postrenal transplant, postbone marrow transplant
patients, or those with ulcerative colitis.
Vesely et al reported a case series of 18 patients with
severe ADAMTS-13 deficiency of which 8 developed
Table 1. Selected laboratory test results.

elevated creatinine but none required dialysis. Char-

Platelets: 15,000/mm3

acteristically, they also found that patients with more

Day 1 at outside

WBC: 15,800/mm3

severe ADAMTS-13 deficiency have milder renal

BUN: 100 mg/dL
hospital

DB: 0.6 mg/dL

TB: 2.2 mg/dL

manifestations with a lower incidence of acute renal

Cr: 8.4 mg/dL
Hgb: 6.3 g/dL

LDH: 914 U/L

failure.2 Up to one-third of patients with severe

Hct: 17.3%

ADAMTS-13 deficiency present with autoimmune

features and have positive antinuclear antibody, anti-
double-stretched-stranded DNA, and anticardiolipin
antibodies.2 Our patient with acquired TTP with
absent ADAMTS-13 activity and high inhibitor titer
did not have any features suggestive of autoimmu-
Chemistry

nity clinically or serologically. She also developed

count.

severe renal failure requiring hemodialysis and

CBC

ultimate recovery after intensive therapy.

American Journal of Therapeutics (2012) 19(1) www.americantherapeutics.com
Acquired TTP Associated With Reversible Severe Renal Failure Requiring Hemodialysis
Due to persistent low platelets in our patient despite
daily plasma exchange at the referring hospital, we
took an intensive approach and started her on twice
daily plasma exchange. Our intensive approach in-
cluded steroids, rituximab, cyclosporine, twice daily
plasma exchange, and hemodialysis. We believe that
this was responsible for complete recovery of the
patient. However, the reason for this unusually severe
renal manifestation needs further study.
www.americantherapeutics.com
e55
REFERENCES
1. Tsai HM. The kidney in thrombotic thrombocytic purpura.
Minerva Med. 2007;98:731–747.
2. Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity
in thrombotic thrombocytopenic purpura-hemolytic uremic
syndrome: relation to presenting features and clinical
outcomes in a prospective cohort of 142 patients. Blood.
2003;102:60–68.
American Journal of Therapeutics (2012) 19(1)