Patient 1
A 12-year old, girl of Hispanic origin, presented with petechial rash
and bruising, jaundice, backaches, nausea, and arthralgia. A complete
blood count (CBC) showed thrombocytopenia (11 х
109/L), anemia (Hb; 9.8 g/dl), reticulocytosis
(16.9%), and normal WBC (5.9 х 109/L). The total
bilirubin level was 48 µmol/L, lactate dehydrogenase (LDH) was 514 U/L,
and the Coombs test was negative. A diagnosis of immune thrombocytopenia
(ITP) was made, and intravenous immunoglobulin (IVIG) 1 g/kg body weight
(bw) was administered, with no resulting increase in platelets.
Subsequently, TTP was suspected, and testing revealed severely decreased
activity ADAMTS13, <5%, which confirmed the diagnosis of TTP
and the patient was transferred to our centre. Upon admission, her
examination was remarkable for fatigue, cutaneous haemorrhages, and
uterine bleeding. The patient’s Hb was 5.9 g/dl, schistocytes were 16%,
reticulocytes were 51%, platelets were 16 х 109/L,
and total bilirubin was 54.5 μmol/L. Daily PEX was initiated concomitant
with methylprednisolone 1000 mg for three days i.v. and rituximab 375
mg/m2 twice weekly for three weeks. After 18 PEXs, the
patient’s platelet count stabilised above 150 x 109/L.
However, ADAMTS13 was persistently <5%, and a high level of
the ADAMTS13 factor inhibitor persisted. Two days after PEX was
electively stopped, the patient’s platelet counts dropped again,
triggering the resumption of PEX twice weekly, which maintained the
platelet count above 300 х 109/L. Six weeks after the
patient’s 29th PEX, TTP occurred again, with a drop of
platelets to 10 x 109/L. Thus, because the patient
developed TTP refractory to PEX, rituximab, and glucocorticoids, we
decided to start therapy with bortezomib, 1.3 mg/m2 on
days 1, 4, 8, and 11. After two additional PEXs and one course of
bortezomib the patient’s platelet counts, Hb, and LDH all recovered.
ADAMTS13 activity reached 81%, and remained within normal limits during
5 years of follow-up. She received one additional course of bortezomib
with 21 days interval. There was no toxicity from bortezomib observed,
and IgG serum levels were checked several times during follow-up period,
during which they never dropped below 7 g/L, and at the last follow-up
was 12.4 g/L (figure 1).