Most adult patients with acquired thrombotic thrombocytopenic purpura (TTP) have
autoantibodies that inhibit the von Willebrand factor–cleaving protease ADAMTS13 in
plasma.1 Plasmapheresis with fresh frozen plasma replacement has significantly improved
the survival rates of these patients from less than 10 to 75%.2 Failure to control the possible
underlying autoimmune process leads to relapse after the initial response in up to one
third of patients, however.3 There are also patients with refractory disease that respond
poorly to plasmapheresis.4 With case reports documenting instances where such patients
have responded to various immunosuppressive therapies, we need a promising and non-
toxic treatment in patients with ADAMTS13 deficiency. We report a patient with TTP who
had chronic hepatitis C infection and membranoproliferative glomerulonephritis (MPGN),
diminished plasma ADAMTS13 activity and elevated ADAMTS13 antibody titres. She failed
to respond to various therapeutic modalities. Treatment with rituximab resulted in the
disappearance of her ADAMTS13 antibodies, normalisation of her ADAMTS13 activity,
remission of her thrombotic microangiopathy and nephrotic syndrome, and improved
renal function. This improvement was followed by a flare-up of her previously quiescent
hepatitis C virus (HCV) infection, however.
A 30-year-old woman was first seen in our clinic in 1997 for mild proteinuria (0.53 g/d).
She had been given a blood transfusion during an appendicectomy at the age of 27 years.
On presentation, she was normotensive and had no urinary symptoms. Her full blood
count, urine microscopy, and renal function tests were unremarkable. Her creatinine
clearance was 97 mL/min/1.73 m2 and her serological markers were all negative, except
for a persistently low complement level (C3, 0.7-0.78 g/L; reference range, 0.86-1.84 g/L).
She was HCV antibody–positive but her serum aminotransferase levels were normal.
An ultrasound examination revealed a normal liver and kidneys. She was started on an
angiotensin-converting enzyme inhibitor and remained asymptomatic for the next 9 years,
with proteinuria ranging from 0.19 to 0.77 g/d, and normal renal function. Renal biopsy was
facial puffiness and lethargy. There were no preceding symptoms and she had not taken any
medications, including oral contraceptives. On admission, she was pale and had bilateral
She was hospitalised in March 2006 for a 10-day history of bilateral ankle swelling,
Refractory thrombotic thrombocytopenic purpura
and membranoproliferative glomerulonephritis
successfully treated with rituximab: a case
associated with hepatitis C virus infection
Hepatitis C; Purpura, thrombocytopenic,
idiopathic; Rituximab; Thrombocytopenia
Hong Kong Med J 2009;15:201-8
Renal Unit, Department of Medicine
and Geriatrics, Kwong Wah Hospital,
Kowloon, Hong Kong
SK Mak, FRCP (Edin)
KY Lo, MRCP (UK)
SF Chan, MRCP (UK)
KC Lo, MRCP (UK)
YY Wong, MRCP (UK)
GMW Tong, MRCP (UK)
PN Wong, FRCP (Edin)
AKM Wong, FRCP (London)
Department of Medicine and Geriatrics,
Our Lady of Maryknoll Hospital,
Kowloon, Hong Kong
MW Lo, MRCP (UK)
Department of Clinical Pathology, Hong
Kong Sanatorium and Hospital, Hong
ESK Ma, FRCPath (London)
Correspondence to: Dr SK Mak
Gensy MW Tong
Edmond SK Ma
Andrew KM Wong
Plasmapheresis remains the main treatment modality for patients with thrombotic
thrombocytopenic purpura. We report a patient who had simultaneous onset of
membranoproliferative glomerulonephritis and thrombotic thrombocytopenic purpura. She
did not improve after 48 plasmapheresis sessions. A 6-week course of weekly intravenous
doses of rituximab was then given. This achieved complete remission of her nephrotic
syndrome and improvement in her renal function, so plasmapheresis was ceased. She had
a low ADAMTS13 antigen level and a positive ADAMTS13 antibody, both of which reverted
to normal after treatment with rituximab. This coincided with a rise in her hepatitis C virus
RNA and liver transaminases. Liver biopsies did not reveal active fibrosis. Her hepatitis C virus
RNA titre dropped afterwards, and she had no relapses of her thrombotic thrombocytopenic
purpura and nephrotic syndrome, for more than 2 years after remission. The simultaneous
onset and successful outcomes of both the membranoproliferative glomerulonephritis and
thrombotic thrombocytopenic purpura illustrate the usefulness of rituximab. We discuss its
use and risks, in the context of chronic hepatitis C infection.
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