C‐Reactive Protein Mediates the Association Between Rheumatoid Arthritis and Immune Thrombocytopenia: An Observational and Mendelian Randomisation Study

ABSTRACT Thrombocytopenia has been increasingly observed in patients with rheumatoid arthritis (RA) in clinical practice. However, whether this association reflects a causal relationship remains unclear. This study aims to investigate the causal effect of RA on the risk of developing immune thrombocytopenia (ITP) and to evaluate the potential mediating role of C‐reactive protein (CRP) in this relationship. This study combined a cross‐sectional survey of data from the National Health and Nutrition Examination Survey (NHANES) 2003–2018 and two‐sample Mendelian randomisation (MR) analyses. The observational study utilised multivariable logistic regression to examine the association between RA and ITP. The MR analysis used single‐nucleotide polymorphisms (SNPs) as instrumental variables to evaluate the causal relationship between RA and ITP, as well as the mediating effect of CRP. The observational analysis demonstrated a significant positive association between RA and ITP after full adjustment for confounding variables (OR = 2.92, 95% CI: 1.93–4.44, p < 0.001). This association remained consistent across all predefined subgroups. MR analysis indicated a positive causal effect of genetically predicted RA on ITP risk (OR = 1.218, 95% CI: 1.093–1.356, p < 0.05). Mediation analysis estimated that CRP accounted for approximately 9% (95% CI: 3%–17%) of the total effect. The robustness of both observational and causal findings was upheld through sensitivity analyses. This study demonstrates a significant association between RA and ITP, with CRP partially mediating this relationship.