Bleeding Manifestations and Management of Children with Persistent and Chronic Immune Thrombocytopenia (ITP): Data From the Intercontinental Cooperative ITP Study Group.
Authors: Neunert Cindy , Buchanan George R. , Imbach Paul A. , Bolton-Maggs Paula HB , Bennett Carolyn M. , Neufeld Ellis J , Vesely Sara K. , Adix Leah , Blanchette Victor S. , Kuehne Thomas 
Published: October 2019

Abstract
Abstract 1315
Poster Board I-339
ITP during childhood is generally characterized by acute onset of thrombocytopenia and bleeding in an otherwise well child. While the platelet count has traditionally been viewed as a marker of disease severity, additional patient characteristics such as bleeding severity have not been well defined. The Intercontinental Cooperative ITP Study Group (ICIS) Registry II was designed to characterize the location, frequency, timing, and severity of bleeding in children with ITP (Blood, 2008;112: 4003-8). We report here data from Registry II with a focus on bleeding symptoms reported at 6 and 12 months. Patients enrolled on Registry II had research visits at diagnosis, and 28 days, 6 months, 12 months, and 24 months following diagnosis. Bleeding manifestations were retrospectively recorded at 6 and 12 months capturing all sites of bleeding (e.g skin, epistaxis, and gastrointestinal) since the last research visit. Of the 1318 children enrolled at diagnosis, 891 were evaluated at 6 months and 718 at 12 months. Mean platelet counts were 198 × 109/l (s.d. 130) and 195 × 109/l (s.d.122) at 6 and 12 months respectively. At 6 months 29% (261/891) of patients still had a platelet count <100 × 109/l; of these 45% (118/261) were <30 × 109/l. At 12 months these values were 28% (203/718) and 40% (82/203) respectively. Number of bleeding sites reported since the last research visit at 6 months and 12 months are outlined in Table 1. There were no reports of intracranial hemorrhage (ICH) or fatal hemorrhage. The most common bleeding site reported at both 6 and 12 months was skin, followed by epistaxis. 4 children with a platelet count <30 × 109/l at both 6 and 12 months were reported as having undergone splenectomy. Red cell transfusions were infrequent (3 reported) and administered only in children with bleeding from ≥ 3 sites. The percentage of patients with a platelet count <30 × 109/l who received platelet count enhancing therapy (including platelet transfusions) is outlined in Table 2.
Table 1 Number of bleeding sites reported since last research visit at 6 and 12 months 6 month visit 12 month visit Number of sites Platelet count <100 × 109/l (n= 261) Platelet count <30 × 109/l (n= 118) Platelet count <100 × 109/l (n= 203) Platelet count <30 × 109/l (n= 82) None 60 (23%) 10 (9%) 74 (36%) 16 (19%) 1 110 (42%) 44 (37%) 82 (40%) 33 (40%) 2 61 (23%) 39 (33%) 32 (16%) 21 (26%) 33 30 (12%) 25 (21%) 15 (7%) 12 (15%)
Table 2 Patients with platelet count <30 × 109/l reported as having received platelet count enhancing therapy Number of bleeding sites reported between research visits Treatment reported between 28 days and 6 months (n = 118) Treatment reported between 6 and 12 months (n = 82) None 1/10 (10%) 4/16 (8%) 1 29/44 (66%) 19/33 (58%) 32 58/64 (91%) 26/33 (78%)
In summary, approximately 30% of children with ITP enrolled on ICIS Registry II remain thrombocytopenic 6 and 12 months later, many still having a platelet count <30 × 109/l, a threshold value sometimes used to determine drug treatment and enrollment in prospective intervention studies. This cut-off may be appropriate since bleeding was more common when the platelet count was <30 × 109/l. However, even below this threshold life-threatening hemorrhage was uncommon, few patients required packed red blood cell transfusions, and approximately half the patients reported no more than one site of bleeding. Treatment was infrequently used in patients in this group if they had no bleeding, and platelet enhancing therapy was often employed if more bleeding sites were involved. These data suggest a trend towards reserving treatment for patients with more severe bleeding manifestations rather than because of a specific platelet count.

Disclosures
Buchanan: AMG 531: Research Funding. Bolton-Maggs:Baxter: Travel support to meetings; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; United Kingdom Immune Thrombocytopenic Pupura Support Association: Research Funding; Glaxo Smith Kline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Blanchette:AMG 531: Membership on an entity's Board of Directors or advisory committees. Kuehne:F. Hoffman-La Roche Ltd: Research Funding; Amgen: Research Funding.