Background: Immune thrombocytopenia (ITP) is an au-toimmune disease, has been defined as isolated thrombocyto-penia driven on by platelet destruction via platelet autoanti-bodies and/or T-cell-mediated damage. Applying guidelines in resource-constrained healthcare systems is usually difficult as a result of the limitations associated with the use of more ex-pensive second-line therapeutics. Determining the predictors of therapeutic response is a much-needed step in the management of ITP. Aim of Study: This study aimed to identify the outcome of second-line therapy together with the predictive factors for re-sponse in patients with persistent and chronic ITP. Patients and Methods: This retrospective cohort multicen-tric study was carried out by retrieving data from the records of 103 ITP patients who attended hematology units and outpatient clinics at Kasr Al-Ainy School of Medicine and Maadi Armed Forces Medical Complex between January 2015 and December 2021. The data included demographic data, clinical findings, di-agnostic procedures, including BM examination (if performed) and therapeutic interventions. The collected data were statisti-cally analyzed. Results: The complete response (CR) rate to splenecto-my was 30% at 6 months and 17% at 12 months postsurgery, whereas the CR rate for TPO-RAs treatment was 33.3% at 6 months after the onset of treatment. In patients treated with splenectomy, CR was significantly associated with previous use of mycophenolatemofetil. Previous diagnosis and H. pylori infection eradication were linked to increased CR in patients receiving TPO-RAs treatment. Conclusion: Treatment of ITP patients with TPO-RAs might lead to a better CR than that after splenectomy at 6 months. Further studies are recommended to explore the possi-ble predictors of response.