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Objectives Evidence-based data on the management of thrombocytopenia in systemic lupus erythematosus (SLE) and the platelet threshold for initiating therapy remain limited. This study aimed to evaluate treatment responses in patients with severe immune thrombocytopenia associated with SLE (SLE-ITP) and to assess the impact of thrombocytopenia severity on treatment outcomes.Methods In this retrospective, multicenter study, patients fulfilling the 2019 EULAR/ACR criteria for SLE and presenting with severe SLE-ITP(<50,000/mm 3) with at least 6 months follow-up were included. Thrombocytopenia was categorized as severe (30–50,000/mm3) and very severe (<30,000/mm3). Demographics and treatment responses were systematically evaluated.Results A total of 100 patients (female/male:83/17) were included; median follow-up of 76.8 months(IQR 35.5–105.3) and mean age was 45.5±14.4 years. Mean initial platelet count was 22,500±13,900/mm 3 (32-severe ITP,68-very severe ITP). Major bleeding occurred in 3 and minor in 37 patients, more frequent in the very severe group (2 major and 31 minor vs. 1 major and 6 minor;p<0.01).As initial therapy, 99% of patients received corticosteroids(CS) and 18% received IVIg(17 in combination with CS, 1 with IVIg alone). Early response within the first month was observed in 94 patients. Sixty six percent of patients received steroid-sparing immunosuppressive agents(IS) as part of initial therapy, whereas 33% received CS alone. During the follow-up, second-line treatment was required in 39 patients due to failure(n=24) or relapse(n=15), including 19/66(28.7%) in the IS group and 20/33(60.6%) in the CS-only group(p=0.004). Overall response to second-line therapy was 87.1%(34/39). Median time to relapse was 23.3 months (IQR 5–38), and 4 patients remained refractory.Multivariate analysis showed delayed IS initiation and low hemoglobin were significantly associated with poorer treatment response (OR:4.7,95%CI 1.7–12.8, p=0.002; OR:1.5,95% CI 1.1–1.9,p=0.001). No association was observed between thrombocytopenia severity and response (p>0.05).Abstract PO:10:251 Table 1Treatment responses to immunosuppressive agents according to thrombocytopeniaseverityAbstract PO:10:251 Figure 1Treatment response rates of patients during follow-upConclusions Early initiation of IS therapy was associated with improved treatment response. Although 30,000/mm 3 is often considered the threshold for initiating therapy, our study showed ~20% of patients with 30-50,000/mm3 still experienced bleeding, including one major event. No differences in response rates were observed by thrombocytopenia severity, highlighting the need for careful monitoring of patients with platelets <50,000/mm3 and reconsideration of the treatment threshold.