Baylor University Medical Center Proceedings April 2017 - 183

alternate complement pathway, we
initiated treatment with the anti-
complement 5 monoclonal antibody eculizumab, following which
the patient had durable remission
that continued for 30 months after
discontinuation of the drug. We
later found out that our patient
had a large homozygous deletion
in complement factor H-related 1
and complement factor H-related
3 genes in the alternate complement
pathway. This could explain the durable remission that she achieved
with eculizumab.
This case, along with the other
two reported cases with simultaneous occurrence of severe idiopathic
TTP and the presence of alternate
complement pathway mutations, argues for a common shared pathogenesis in TTP and atypical hemolytic
uremic syndrome disease processes.
Identifying the underlying complement genetic defects in severe
ADAMTS13-deﬁcient patients may
help us to predict the poor response
of this subset of TTP patients to plasFigure. Response to eculizumab in a patient with severe acquired idiopathic thrombotic thrombocytopenic purpura re- ma exchange and to explore diﬀerent
fractory to standard treatment. Daily plasma exchange (TPE) and steroids were begun on admission, and vincristine and treatment options.
weekly rituximab infusions were initiated as shown. Lactate dehydrogenase (LDH) was 729 U/L on admission, increasing
to 1620 on day 14. Plasma exchange was discontinued, and eculizumab, 900 mg intravenously, was added on day 17.
Rapid improvement in mental status and laboratory abnormalities occurred following administration of eculizumab. Her
platelet count normalized within 15 days, and her ADAMTS13 activity normalized by day 30.

syndrome having reduced levels of ADAMTS13; however, these
patients did not have an ADAMTS13 inhibitor, as was seen in our
patient (5). There is a case of congenital ADAMTS13-deﬁcient
TTP that was also found to have a heterozygous mutation in the
complement factor H gene (6).
Recent studies have described the importance of the complement system in all forms of thrombotic microangiopathies.
Excessive alternate complement pathway activity has been
reported to occur in a signiﬁcant number of TTP patients,
indicating the presence of concurrent defects in ADAMTS13
and complement regulation (7). Evidence that complement
activation might play a role in pathogenesis of TTP suggests
a role for complement-inhibiting drugs in this disease. There
is one reported case of congenital TTP that was successfully
treated with eculizumab in spite of negative atypical hemolytic
uremic syndrome genetic testing (8). There is one other case
in the literature where a refractory acquired TTP was treated
successfully with eculizumab. This patient was also found to
have complement factor H gene polymorphism, which could
explain the response to the eculizumab (9).
Theorizing that our patient either had concurrent atypical
hemolytic uremic syndrome or had TTP with a dysregulated
April 2017

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4.

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8.

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Acquired thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome successfully treated with eculizumab

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