To evaluate clinical characteristics, therapeutic response and long-term prognosis in patients with primary Sjögren’s disease–associated immune thrombocytopenia (pSjD-ITP).

An ambispective cohort study was conducted on patients with pSjD treated at the China-Japan Friendship Hospital between 2013 and 2023. Variables associated with treatment outcomes were identified through LASSO regression, Boruta feature selection, and stepwise regression, with SHAP analysis used to visualize key variable contributions. Follow-up assessments captured therapeutic response, relapse, and mortality in pSjD-ITP.

Among 1347 pSjD patients in this study, 7.8% had ITP and exhibited a distinct clinical phenotype, with a treatment response achieved in 73%. Five independent predictors of therapeutic response were identified: D-dimer (OR = 2.479, p = 0.024), platelet count < 20 × 10⁹/L (OR = 4.800, p = 0.0495), prothrombin time (PT; OR = 0.478, p = 0.010), age (OR = 1.034, p = 0.142), and cutaneous hemorrhage (OR = 4.110, p = 0.192). A predictive model incorporating these variables demonstrated robust discriminative ability (AUC = 0.829), excellent calibration, and favorable clinical utility, with consistent performance on internal validation. Among responders, 31.7% experienced relapse. Elevated activated partial thromboplastin time (APTT; HR = 1.028, p = 0.002) and baseline blood transfusion (HR = 3.716,  p = 0.028) were significantly associated with increased relapse risk. All-cause mortality of pSjD-ITP was 16.3%. Independent risk factors for death included elevated gamma-glutamyl transferase (GGT; HR = 1.004, p < 0.001), elevated lactate dehydrogenase (LDH; HR = 1.010, p = 0.002), dyspnea (HR = 4.289, p = 0.023), and age (HR = 1.065, p = 0.032).

This study established a novel predictive model to distinguish treatment responders in pSjD-ITP. Elevated APTT and baseline blood transfusion were associated with relapse, while elevated GGT and LDH, dyspnea, and older age were risk factors for death, highlighting the need for risk-stratified and personalized management of pSjD-ITP.