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).