Immune Thrombocytopenia (ITP) is one of the most common acquired bleeding disorders affecting children. While 75-80% of these children will develop only mild bleeding symptoms, others can experience more severe bleeding, including rare intracranial hemorrhage (ICH), and may require platelet-directed therapy. Intravenous immunoglobulin (IVIG), a commonly utilized and effective first-line therapy, may be associated with adverse drug events (ADEs). The most commonly reported ADEs include headache (approximately 30% of treated patients) and nausea/vomiting, however the exact rates of these events and relationship to premedication strategies are poorly classified. These ADEs often result in emergent medical evaluation and additional diagnostic testing, including computed tomography (CT) of the head, to evaluate for ICH in children with severe thrombocytopenia.In order to identify rates of IVIG-associated ADEs and subsequent emergent medical evaluations in pediatric patients with ITP, we completed an retrospective observational cohort study of all pediatric patients with ITP who were treated with one-time IVIG infusion utilizing Gamunex-C ® 10% at a dose of 1g/kg across 4 large pediatric centers from 2010 to 2019. Included patients were between the ages of 0 and 21 years.Among the 563 patients receiving single IVIG infusions across all 4 centers, patients reported headache, nausea/vomiting, or both following 203 infusions (36%). Excluding those patients who remained hospitalized at the time of symptom development, 16% (84 of 513) of all patients returned for urgent medical evaluation following IVIG infusion. Nine percent of all patients receiving a single IVIG infusion underwent head CT to rule out ICH. All 51 CTs were negative for ICH.In order to determine if specific patient characteristics were associated with the development of IVIG-associated ADEs and return to medical care, univariable logistic regression was performed. Multiple logistic regression was used to determine whether the associations identified in the univariable analysis persisted after adjusting for other significant factors. Older age at administration (Adjusted Odds Ratio [adj OR] 1.07 for each additional year of age; 95% Confidence Interval [CI] 1.03, 1.11; p<0.001) and premedication with hydrocortisone (adj OR 2.36; 95% CI 1.38, 4.07; p=0.002) were associated with increased odds of IVIG-associated ADEs. Patients who received premedication with hydrocortisone were more likely to re-present for medical evaluation than patients who did not receive hydrocortisone (OR 1.90; 95% CI 0.98, 3.54; p=0.049). No associations were identified between ADEs and gender, race/ethnicity, premedication with diphenhydramine or ondansetron, pre-treatment serum IgG levels, or concurrent glucocorticoid administration.In summary, the rate of ADEs among pediatric patients with ITP treated with IVIG is remarkably high. Thirty-six percent of patients in our multi-institutional cohort reported headache, nausea/vomiting, or both following single IVIG infusion, consistent with our previous single institution experience. This again highlights the need for proper balance of risks and benefits when considering treatment for children with ITP. Patients who received premedication with acetaminophen were less likely to develop IVIG-associated ADEs, but those who received premedication with diphenhydramine or concurrent glucocorticoid therapy were no more or less likely to develop ADEs. Interestingly, however, patients who received premedication with hydrocortisone were more likely to develop IVIG-associated ADEs. Despite only a small subset of our cohort being premedicated with hydrocortisone (12%, n=66), this premedication strategy was significantly associated with an increased rate of return to medical care following IVIG infusion. Patients returning for emergent medical evaluation frequently underwent repeat laboratory studies or CT imaging, resulting in unnecessary radiation exposure and increased healthcare-related costs. These findings will help to inform IVIG premedication strategies in an attempt to reduce both ADEs and re-presentation to medical care among pediatric patients with ITP receiving IVIG therapy. [Display omitted] DisclosuresKirk: Biomarin: Honoraria. Grace: Novartis: Research Funding; Principia: Membership on an entity's Board of Directors or advisory committees; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Research Funding. Neunert: Novartis: Research Funding. Lambert: Bayer: Consultancy; ClinGen, ISTH, ASH, GW University: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Astra Zeneca: Research Funding; Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dova: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; PDSA: Research Funding; Sysmex: Research Funding; Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Despotovic: UpToDate: Patents & Royalties: Royalties; Apellis: Consultancy; Novartis: Consultancy, Research Funding; Agios: Consultancy.