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

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.