Abstract
Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition requiring rapid diagnosis and treatment. Plasma exchange (PEX) is the mainstay of treatment. Various forms of immunosuppression (IS) have been used which include steroids, cyclosporine, cyclophosphamide, vincristine and rituximab. The percentage of patients relapsing is unclear. There is a suggestion that up to half of the patients with severe acquired deficiency of von Willebrand factor -cleaving protease (vWF-CP) activity relapse within a year. There are no reports of the use of mycophenolate mofetil (MMF) in acquired TTP. We describe three patients with acquired TTP, treated with MMF at relapse, with the intention to prevent further relapse.
Methods: The 3 patients presented with acute acquired TTP. They all had at least 3 of the clinical pentad of fever, microangiopathic haemolytic anaemia, thrombocytopenia, neurological and renal impairment plus a vWF-CP level of < 2% at initial presentation. All of them underwent PEX until remission (platelet count of >150 x 109/L for at least 2 consecutive days with resolution of neurological and renal signs). MMF was introduced at remission after relapse at a dose of 500mg BD, post PEX, increasing upto a maximum dose of 750 mg BD. MMF was introduced at 4th relapse for patient A, 2nd relapse for patient B and 1st relapse for patient C.
Results: All 3 patients were females. The ages at presentation were 63, 72 and 46 years. At presentation, the haemoglobin was 6.0, 8.7 and 6.7 g/dL and platelet count was 19, 36 and 21 x 109 /L respectively. Patient A relapsed eight times at day (d) 9, d20, d53, d89, d198, d209, d221 and d231. She was treated with PEX in conjunction with steroids and vincristine, cyclosporine, cyclophosphamide and rituximab for the first 3 relapses respectively. During the third relapse the patient’s condition deteriorated and she became unconcious requiring ventilation. MRI brain showed multiple small foci consistent with vascular disease. She recovered, but relapsed again despite cyclophosphamide and rituximab. After the 4th relapse on d102, MMF was started reaching a maximum dose of 750mg BD. She had regular full blood counts checked. At d187 she was found to be neutropenic and the MMF was stopped. She relapsed in 11 days and was recommenced on MMF at 500mg bd after PEX. MMF was continued at the dose of 750mg BD after the 7th and 8th relapse. Despite full dose MMF, she relapsed and was treated with PEX and a further course of rituximab was given at the 8th relapse. Patient B had received 500mg of methyl prednisolone on ITU with PEX at initial presentation. MMF (500mg BD) was commenced at remission after second relapse (d23) after undergoing plasma exchange. Patient C was commenced on MMF (500mg BD) after first relapse (d36). All 3 are in remission and continue on MMF at a follow up of 12, 2 and 4 months respectively since last relapse. MMF was tolerated very well except for transient neutropenia (patient A) and transient diarrhoea (patient C).
Conclusion: MMF appears to be safe in patients with relapsed TTP who received multiple lines of treatment. Due to the small size of this case series it is unclear whether MMF is efficacious in reducing the risk of relapse in TTP; a formal longer study may be warranted.
Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura