The Results of the Russian Registry of Primary Immune Thrombocytopenia (ITP) in Adults
Authors: Lisukov Igor , Maschan Alexey , Shamardina Anastasia , Chagorova Tatyana , Davydkin Igor , Sycheva Tatyana , Zagoskina Tamara , Karyagina Elena , Salogub Galina , Savinova Marina , Schelekhova Tatyana , Kovaleva Lidiya , Schneider Tatyana , Unzhekova Anna , Kuznetsova Elena , Schatochin Yuriy , Ivanova Maria , Vinogradova Elena , Kaplanov Kamil , Markova Inna , Kanjukova Olimpiada , Abdulkadyrov Kudrat , Sedlova Julia , Osynikhina Svetlana , Tsvetaeva Nina , Volodicheva Elena , Akhmadeev Aryslan , Maschan Michael A , Kulagin Alexandr , Rumyantsev Alexander , Afanasyev Boris V 
Published: October 2019

Abstract
Study objectives
The aim of the study was to evaluate disease characteristics and treatment practices of ITP in Russia.
Materials and methods
The ITP Registry was a multicenter, prospective, observational cohort study. The observation period for each patient in the Registry was not less than 12 months. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient. Exclusion criteria: secondary thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics was used. Patients were registered since June 2011 till June 2014.
Results
Five hundred and seven adult 394female (77.7%)/113 male(22.3%) pts from 26 hematology centers in various regions of the Russian Federation were included. Observation period ranged from 1.4 to 29.8 months with an average of 18.6 ± 6.2 mo. Median age was 50.2 years (range 18.6-89.1).
Median disease duration was 1.83 years (range 0-56.07). History of ITP of lasting < 1 year was reported in 186 (36.7%) pts, 1-5 years - in 142 (28%), 5-10 years - in 56 (11%), over 10 years - in 87 (17.2%), and was considered as unknown - in 36 (7.1%).
Newly diagnosed ITP was reported in 19.5% of adult pts; persistent - in 16.6% and chronic ITP - in 63.9% of pts, respectively. Median platelets count was 14,0 x 109/L (range 0.0- 119.0 x 109/L). Hemorrhagic manifestations in the history of ITP were reported in 92.5% of pts: skin hemorrhages - in 89.5% of pts, oral bleeding - in 50.3% , epistaxis - in 37.3% , gastrointestinal bleeding - in 7.7%, intracranial bleeding - in 0.4%, hematuria - in 4.5%, and other hemorrhages - in 20.9% of pts. Severe ITP at the time of enrollment was observed in 158 (31.2%) pts (104 pts (20.5%) had a clinically significant bleeding at the disease onset, and 54 (10.7%) pts developed new clinically significant hemorrhages during the treatment. Refractory ITP at the time of enrollment was reported in 100 (19.7%) pts (resistance to the first, second and subsequent lines of therapy in 62 (12.2%) pts); 38 (7.5%) pts did not respond to splenectomy. At the time of enrollment, 250 (49.3%) pts received medical treatment for ITP.
Severe ITP after enrollment was observed in 124 (24.8%) adult pts. Throughout the study, various hemorrhagic manifestations of ITP were reported in 48.0% of pts, severe hemorrhagic syndrome was reported in 10.0% of pts;
Before enrollment, splenectomy was reported in 94 pts (18.5%); complete response (CR) was maintained in 34 (36.2%) pts, partial response - in 20 (21.3%), and no response - in 7 (7.4%). Thirty-two (34.0%) pts had lost the response after initial success. During the study, splenectomy was performed in 44 (10.8%) pts, of those - in 7 pts (15.9%) with newly diagnosed ITP; in 6 pts (13.6%) - with persistent ITP, and in 31 pts (70.5%) - with chronic ITP. The duration of the disease at the time of splenectomy varied from 0 to 21 yrs; with a median of 1.03 year. CR to splenectomy was observed in 31 (70.5%) pts, partial response - in 10 (22.7%), and no response in 1 (2.3%), while 2 (4.5%) pts lost response.
Since the response to splenectomy might change during the observation in the study, the best response was registered.
Table 1. Distribution of the best response to splenectomy variable (before study entry and in the course of the study). Number of Pts (n) % Best response to splenectomy Missing data 1 0.7% Complete response 65 47.1% A response 30 21.7% No response 8 5.8% Loss of response 34 24.6% Total 138 100%
Two hundred and forty-three (47.9%) pts received their first-line treatment during the study; glucocorticosteroids (GCS) - 222 (91.3%) pts, immunoglobulins (IVIG) - 2 pts (0.8%), other drugs - 26 (10.7 %) pts. A second-line therapy was administered to 133 pts (26.23%), of which 27 (20.3%) received GCS, IVIG - 23 (17.3%), alfa-interferons - 6 (4.5%), immunosuppressants - 8 (6%), rituximab - 18 (13.53%), romiplostim - 39 (29.3%), eltrombopag - 37 (27.8%), other drugs - 2 (1.5%) pts.
Conclusion
For the first time in Russia, information regarding the clinical presentation and the "real life" management practice of adults with primary ITP was obtained in a large cohort of pts in a prospective study. The Registry showed a variability of ITP clinical course. One fifth of pts were refractory to therapy. The main therapy options for the ≥ 2nd line in a cohort of adult pts were splenectomy and TPO receptor agonists. However, large proportion of pts still received GCSs in the 2nd and even 3rd line of therapy.

Disclosures
No relevant conflicts of interest to declare.