- Severe Idiopathic Thrombocytopenic Purpura (ITP) is a relatively common disorder with a small but definite associated mortality. For many years, first line therapy has consisted of steroid or Intravenous Immunoglobulin. A plethora of second line treatment options have traditionally included splenectomy, Rituximab, Mycophenolate, other immunosupressants & Danazol. Each has had its own risks and uncertain efficacy and treatment sequencing for refractory patients has always been very much at the discretion of individual clinicians. Recently the Thrombopoietin Receptor Agonists (TPO-RA) Romi-plostim and Eltrombopag have been available in the UK (NICE approved in 2011 and 2013 respectively). Both are regarded as highly effective but costly treatments. We present here our recent experience of using TPO-RA in a large clinical unit serving a population of 600,000. We audited patients on TPO-RA between March 2016 and April 2017. TPO-RAs were used in 34 episodes (30 patients, 4 patients required switching from one to other). Eltrombopag was used in 25 episodes and Romi-plostim in 9 episodes. Patient demographics were as follows: 21 females, 9 males; Age range 28-91 (median 65.4). 26 out of 30 patients were treated in accordance with NICE guidance. These patients were refractory to other standard treatment for ITP and/or had severe disease and a high risk of bleeding requiring frequent rescue therapy. Splenectomy was considered inappropriate in 20 out of 26 (76.9%) patients. 6 out of 26 (23%) patients were post splenectomy and had refractory ITP. 4 out of 30 patients were treated with TPO (Eltrombopag) out with NICE guidance. Splenectomised patients had a median of 5.5 previous treatment lines compared with non-splenectomised patients (1.36). Eltrombopag doses ranged from 25-75 mg/day. Romiplostim doses ranged from 2-10 mcg/kg/week. 4 patients switched between Romiplostim and Eltrombopag due to loss/failure of response. Doses were individualized to maintain platelet counts in a safe range. All patients showed a positive response to one or the other agent (defined as greater than 50 x 10/l) In general both treatments were well tolerated and no drug needed discontinuation due to side effects. Main side effects with Eltrombopag were fatigue (2 patients), headache (2) and grade 1 diarrhoea (1). Side effects experienced with Romiplastim were dyspepsia (1) and occasional mild headache (1). In our experience TPO-RA treatments are well tolerated and all patients audited showed an effective response. Furthermore, we also noticed that our clinicians do not consider splenectomy to be a favoured second line treatment in the era of TPO-RAs. This suggests that the current treatment paradigm should be reviewed.