title: Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.
abstract: 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.
authors.affiliation: Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.affiliation: UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.affiliation: S.C. Di Ematologia Ospedale Nigurda Ca' Granda, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantoni
authors.affiliation: U.O Ematologia E Trapianto, a.O San Gerardo Di Monza E Università Di Milano Bicocca, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Carpenedo
authors.affiliation: U.O.C. Di Ematologia, P.O. S. G. Moscati, Aversa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caparrotti
authors.affiliation: SODc Ematologia, AOU Careggi, Firenze, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carrai
authors.affiliation: U.O. Di Ematologia E Trapianto Cellule Staminali, Lecce, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.affiliation: Dipartimento Di Biotecnologie Cellulari Ed Ematologia, , "Sapienza" Università Di Roma, Roma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santoro
authors.affiliation: Unità Di Immunoterapia Clinica E Terapie Innovative, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Clinica Ematologica, Dipartimento Di Medicina, Sezione Di Ematologia, Azienda Ospedaliera Universitaria Integrata Di Verona, Verona, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Veneri
authors.affiliation: UOS Ematologia Ospedale Versilia USL12 Lido Di Camaiore, Camaiore, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Simonetti
authors.affiliation: S.C. Oncoematologia, a.O. Santa Maria, Terni, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: UOC Oncoematologia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ferla
authors.affiliation: Fondazione GIMEMA, Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoloni
authors.affiliation: Fondazione GIMEMA, Roma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Crea
authors.affiliation: Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volpetti
authors.affiliation: Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Tuniz
authors.affiliation: Clinica Ematologica, DISM, a O U S. M. Misericordia, Udine, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011169:Portal Vein; D011183:Postoperative Complications / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D011292:Premedication; D011300:Preoperative Care / Q000379:methods*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000601:surgery*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000008:administration & dosage / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D013156:Splenectomy; D019851:Thrombophilia / Q000139:chemically induced; D034061:Thrombopoiesis / Q000187:drug effects*; D013926:Thrombopoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020246:Venous Thrombosis / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D001565:Benzoates; D006834:Hydrazines; D016756:Immunoglobulins, Intravenous; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag