title: Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura.
abstract: It has been suggested that platelet function in chronic immune thrombocytopenic purpura (ITP) may be abnormal. Thrombopoietin mimetics used for treatment can affect it, but the data remain limited. We investigated platelet function of 20 children diagnosed with severe ITP (aged 1-16 years, 12 females and eight males). Platelet functional activity in whole blood was characterized by flow cytometry before and after stimulation with SFLLRN plus collagen-related peptide. Levels of CD42b, PAC1, and CD62P, but not CD61 or annexin V, were significantly increased (P < 0.05) in resting platelets of patients before treatment compared with healthy donors. On average, PAC1 and CD62P in patients after activation were also significantly elevated, although some patients failed to activate integrins. Romiplostim (1-15 μg/kg/week s.c.) was prescribed to seven patients, with clinical improvement in six. Interestingly, one patient had clinical improvement without platelet count increase. Eltrombopag (25-75 mg/day p.o.) was given to four patients, with positive response in one. Others switched to romiplostim, with one stable positive response, one unstable positive response, and one non-responding. Platelet quality improved with romiplostim treatment, and their parameters approached the normal values. Our results suggest that platelets in children with severe ITP are pre-activated and abnormal, but improve with treatment.
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Suntsova
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Irina M
authors.initials: IM
authors.lastname: Demina
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Ignatova
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Nikolay M
authors.initials: NM
authors.lastname: Ershov
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Trubina
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Juliya
authors.initials: J
authors.lastname: Dobrynina
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Serkova
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Zhanna S
authors.initials: ZS
authors.lastname: Supik
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Orekhova
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Lili A
authors.initials: LA
authors.lastname: Hachatryan
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Kotskaya
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Pshonkin
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Aleksey A
authors.initials: AA
authors.lastname: Maschan
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Novichkova
authors.affiliation: National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, 117198, Moscow, Russia. mapanteleev@yandex.ru.|Center for Theoretical Problems of Physicochemical Pharmacology, 119991, Moscow, Russia. mapanteleev@yandex.ru.|Faculty of Physics, Moscow State University, 119992, Moscow, Russia. mapanteleev@yandex.ru.|Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700, Dolgoprudny, Russia. mapanteleev@yandex.ru.
authors.forename: Mikhail A
authors.identifier: http://orcid.org/0000-0002-8128-7757
authors.initials: MA
authors.lastname: Panteleev
mesh_terms: D000293:Adolescent; D017304:Annexin A5 / Q000097:blood; D015703:Antigens, CD / Q000097:blood; D001565:Benzoates / Q000008:administration & dosage*; D001792:Blood Platelets / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage*; D011961:Receptors, Fc / Q000008:administration & dosage; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D013926:Thrombopoietin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag
keywords: Eltrombopag; Flow cytometry; Immune thrombocytopenia; Platelet function; Romiplostim