[Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study].

Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.

Weber E ，Moulis G ，Mahévas M ，Guy C ，Lioger B ，Durieu I ，Hunault M ，Ramanantsoa M ，Royer B ，Default A ，Pérault-Pochat MC ，Moachon L ，Bernard N ，Bardy G ，Jonville-Bera AP ，Geniaux H ，Godeau B ，Cathébras P ... -  《-》

Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended.

Zaja F ，Barcellini W ，Cantoni S ，Carpenedo M ，Caparrotti G ，Carrai V ，Di Renzo N ，Santoro C ，Di Nicola M ，Veneri D ，Simonetti F ，Liberati AM ，Ferla V ，Paoloni F ，Crea E ，Volpetti S ，Tuniz E ，Fanin R ... -  《-》

The use of thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): a "real life" retrospective multicenter experience of the Rete Ematologica Pugliese (REP).

Mazza P ，Minoia C ，Melpignano A ，Polimeno G ，Cascavilla N ，Di Renzo N ，Specchia G ... -  《-》

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia.

Lozano ML ，Mingot-Castellano ME ，Perera MM ，Jarque I ，Campos-Alvarez RM ，González-López TJ ，Carreño-Tarragona G ，Bermejo N ，Lopez-Fernandez MF ，de Andrés A ，Valcarcel D ，Casado-Montero LF ，Alvarez-Roman MT ，Orts MI ，Novelli S ，Revilla N ，González-Porras JR ，Bolaños E ，Rodríguez-López MA ，Orna-Montero E ，Vicente V ... -  《-》

Thrombopoietin receptor agonist switch in adult primary immune thrombocytopenia patients: A retrospective collaborative survey involving 4 Spanish centres.

To describe the reasons for and result of thrombopoietin receptor agonists (TPO-RA) switching in adult immune thrombocytopenia (ITP) patients of 4 Spanish centres. We retrospectively analysed all patients who received sequential treatment with both TPO-RA between 2010 and 2015 recording clinical and biological parameters. Twenty-six patients were included; 17 received first romiplostim and 9 received first eltrombopag. Reasons for switching were inefficacy (n = 10), patient preference (n = 8), side effects (n = 5) and excessive platelet count fluctuation (n = 3). When the switch was due to inefficacy, 100% of patients who received romiplostim first and 66% who received eltrombopag first responded to the second drug. It is significant that none of the patients who received romiplostim first reached the maximum recommended dose before switching. When the change was due to patient preference or because of side effects, 100% of the patients responded to both TPO-RA. Three patients changed from romiplostim to eltrombopag due to platelet count fluctuation; one did not respond and the fluctuation persisted in the remaining 2 patients. We also found 4 sustained remissions after administering the second TPO-RA, 2 of these with inefficacy of the first drug. TPO-RA switching is a feasible strategy in different scenarios with high probability of success.

Lakhwani S ，Perera M ，Fernández-Fuertes F ，Ríos de Paz MA ，Torres M ，Raya JM ，Hernández MT ... -  《-》