E Weber1, G Moulis2, M Mahévas3, C Guy4, B Lioger5, I Durieu6, M Hunault7, M Ramanantsoa8, B Royer9, A Default10, M-C Pérault-Pochat11, L Moachon12, N Bernard13, G Bardy14, A-P Jonville-Bera15, H Geniaux16, B Godeau3, P Cathébras17. 1. Service de médecine interne, CHU de Saint-Étienne, hôpital Nord, 42055 Saint-Étienne cedex 2, France. Electronic address: emm.weber@sfr.fr. 2. Service de médecine interne, CHU de Toulouse, France; UMR 1027 Inserm, université de Toulouse, France; CIC 1436, axe pharmaco-épidémiologie, CHU de Toulouse, France. 3. Service de médecine interne, centre de références des cytopénies auto-immunes, UPEC, hôpital Henri-Mondor, AP-HP, 94010 Créteil cedex, France. 4. Centre régional de pharmacovigilance, CHU de Saint-Étienne, hôpital Nord, 42055 Saint-Étienne cedex 2, France. 5. Service de médecine interne, hôpital Bretonneau, CHRU de Tours, GICC-UMR 7292, 37044 Tours cedex 9, France. 6. Service de médecine interne et médecine vasculaire, groupe hospitalier sud, hospices civils de Lyon; université de Lyon, 69495 Pierre-Bénite cedex, France. 7. Service des maladies du sang, CHU d'Angers, 49933 Angers cedex 9, France. 8. Service de médecine interne et infectiologie, centre hospitalier de Nevers, BP 649, 58033 Nevers cedex, France. 9. Service d'hématologie clinique et thérapie cellulaire, hôpital Sud, CHU d'Amiens, 80054 Amiens cedex 1, France. 10. Centre régional de pharmacovigilance, CHU de Marseille, hôpital Sainte-Marguerite, AP-HM, 13009 Marseille cedex 9, France. 11. Centre régional de pharmacovigilance, CHRU Pavillon-le-Blaye, secteur nord-n(o) 6, BP n(o) 577, 86021 Poitiers cedex, France. 12. Centre régional de pharmacovigilance, groupe hospitalier Cochin, bâtiment Lavoisier, 75014 Paris, France. 13. Centre régional de pharmacovigilance, hospices civils de Lyon, 9424 Lyon cedex 03, France. 14. Centre régional de pharmacovigilance, pavillon Victoria, hôpital de Cimiez, CS 91179, 06003 Nice cedex 1, France. 15. Centre régional de pharmacovigilance, CHRU, 37044 Tours cedex 09, France. 16. Centre régional de pharmacovigilance, CHU bâtiment CBRS, 87042 Limoges cedex, France. 17. Service de médecine interne, CHU de Saint-Étienne, hôpital Nord, 42055 Saint-Étienne cedex 2, France.
Abstract
INTRODUCTION: 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. METHODS: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. RESULTS: 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). CONCLUSIONS: 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.
INTRODUCTION: 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. METHODS: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. RESULTS: 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). CONCLUSIONS: 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.
Authors: Maria L Lozano; Maria E Mingot-Castellano; María M Perera; Isidro Jarque; Rosa M Campos-Alvarez; Tomás J González-López; Gonzalo Carreño-Tarragona; Nuria Bermejo; Maria F Lopez-Fernandez; Aurora de Andrés; David Valcarcel; Luis F Casado-Montero; Maria T Alvarez-Roman; María I Orts; Silvana Novelli; Nuria Revilla; Jose R González-Porras; Estefanía Bolaños; Manuel A Rodríguez-López; Elisa Orna-Montero; Vicente Vicente Journal: Sci Rep Date: 2019-11-13 Impact factor: 4.379