Primary immune thrombocytopenia (ITP) is an autoimmune disease in which the number of blood platelets is reduced, which increases the risk of bleeding and worsens the quality of life of patients. The study compared the effectiveness of low-dose rituximab alone and in combination with thalidomide in 100 adult patients who had failed first-line steroid therapy. The combination of thalidomide with rituximab (79.17% success rate) was significantly more effective than rituximab alone (55.32% success rate). Patients with lower baseline levels of natural killer cells (NK cells) showed better therapeutic responses. The number of NK cells increased from 84.63 to 138.71 cells/μl in the combined group after six months of treatment. The study identified baseline NK cell levels as a useful biomarker for predicting treatment success, with a threshold of 110.5 cells/μl having a sensitivity of 81.6% and a specificity of 100%.