Baylor University Medical Center Proceedings April 2017 - 182

Acquired thrombotic thrombocytopenic purpura and atypical
hemolytic uremic syndrome successfully treated with
eculizumab
Appalanaidu Sasapu, MD, Michele Cottler-Fox, MD, and Pooja Motwani, MD

Acquired idiopathic thrombotic thrombocytopenic purpura is a lifethreatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition
who presented with left-sided weakness and seizure-like activity preceded
by headache and easy bruising. She did not achieve optimal response to
plasma exchange, corticosteroids, rituximab, and vincristine. We initiated
treatment with eculizumab, following which she had durable remission that
continued for 30 months after discontinuation of the drug. We later found
that our patient has homozygous deletion in two closely related genes,
complement factor H-related 1 and complement factor H-related 3.

e report an unusual case of thrombotic microangiopathy with ADAMTS13 <5% and an inhibitor that
did not respond to conventional treatment for thrombotic thrombocytopenic purpura (TTP), but was
treated successfully with eculizumab. The patient later tested positive for a classic mutation in the alternate complement pathway
consistent with concurrent atypical hemolytic uremic syndrome.

CASE PRESENTATION
A 64-year-old black woman with diabetes mellitus and
hypertension presented with left-sided weakness and seizure-like activity preceded by 2 days of headaches and 2 weeks of easy bruising.
On admission, her vital signs and physical exam were unremarkable.
Her basic metabolic proﬁle, antinuclear antibody panel, and testing
for hepatitis, HIV, and anti-phospholipid antibody were negative.
Her hemoglobin was 9.0 g/dL, platelets were 13 K/μL, lactate dehydrogenase was 954 IU/L, haptoglobin was <30 mg/dL, and blood
smear showed 4 to 5 schistocytes/high power ﬁeld. ADAMTS13
activity was <5%, and there was an inhibitor level of 1.1 Bethesda
units. Her complement 3 level was 75.3 (normal 90-180 mg/dL),
and complement 4 was <10 mg/dL (normal 15-45 mg/dL).
On hospital day 1, she was started on oral prednisone and daily
therapeutic plasma exchange. After 6 days of plasma exchange without signs of improvement, the ﬁrst dose of rituximab 375 mg/m2
was given on hospital day 7. During the second week of hospitalization, the patient developed delirium and altered mental status.
Magnetic resonance imaging of the brain showed small left frontal
and right occipital lobe infarcts. On hospital day 13, vincristine
2 mg intravenous was given, and on hospital day 14 she received
182

a second dose of rituximab. Her renal function was still normal.
Due to declining mental status, severe thrombocytopenia, and
continued hemolysis, a decision was made on hospital day 17 to
stop plasma exchange and administer eculizumab 900 mg. After
the second dose of eculizumab on hospital day 24, her platelets
improved to 117 K/μL and continued to rise (Figure). Eculizumab
900 mg was given weekly for 4 weeks for a total of 4 doses, after
which ADAMTS13 activity was 75% and the inhibitor was undetectable. Eculizumab 1200 mg was then given every 2 weeks, for
a total of 4 doses. The last dose of eculizumab was on day 90, at
which time her blood work was normal, with ADAMTS13 activity
of 73% and a negative inhibitor screen. Eculizumab was stopped
after 8 doses at the patient's request, and after approximately 3 years
of close follow-up her labs remained normal.
We sent blood for atypical hemolytic uremic syndrome 12-gene
panel testing to Machaon Diagnostics Laboratory 2.5 years after
the diagnosis. The testing revealed a large homozygous deletion in
complement factor H-related 1 and complement factor H-related 3
genes. Also, the patient had a heterozygous missense variant (c.3019
G>T; V1007L) in exon 19 of complement factor H. She had heterozygous polymorphism (IVS9-78G>A) within an intron in MCP/
CD46. Complement factor H autoantibody was not detected.
DISCUSSION
Thrombotic thrombocytopenic purpura is characterized by
a congenital or acquired deﬁciency of the von Willebrand factor
cleaving protein ADAMTS13. Anti-ADAMTS13 autoantibodies
contribute to the pathogenesis of acquired TTP (1, 2). Idiopathic
TTP caused by ADAMTS13 deﬁciency tends to relapse (3), although rituximab has been reported to decrease the risk of relapse
(4). Atypical hemolytic uremic syndrome is caused by alternate
complement pathway dysregulation due to mutations in complement factor H, factor I, factor B, or membrane cofactor protein
(3). There are reports of patients with atypical hemolytic uremic
From the Division of Hematology, Winthrop P. Rockefeller Cancer Institute,
University of Arkansas for Medical Sciences, Little Rock, Arkansas (Sasapu,
Motwani); and the Division of Transfusion Medicine, University of Arkansas for
Medical Sciences, Little Rock, Arkansas (Cottler-Fox).
Corresponding author: Appalanaidu Sasapu, MD, Assistant Professor of
Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St.,
Slot #508, Little Rock, AR 72205 (e-mail: asasapu@uams.edu).
Proc (Bayl Univ Med Cent) 2017;30(2):182-183

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