Within- and Between-Episode Association Between C-Reactive Protein and D-Dimer Across Ordered Assessments in Adults with Clinically Recorded Sepsis: A Secondary Exploratory Single-Center Analysis

Background/Objectives: C-reactive protein (CRP) and D-dimer are routinely measured in sepsis, but it is uncertain whether their repeated values covary within the same hospital episode independently of differences between episodes. We therefore evaluated the same-assessment association between CRP and D-dimer across ordered clinical assessments in adults with clinically recorded sepsis. Methods: This secondary exploratory single-center repeated-measures analysis used 100 admission episodes assessed at M0, M2, and M3; exact elapsed times for M2/M3 and exact phlebotomy timestamps were unavailable. The primary model included 190 CRP–D-dimer pairs from 88 episodes, with 64 episodes contributing at least two pairs. Log-CRP was decomposed into episode-centered and episode-mean components in a random-intercept model adjusted for assessment. Procalcitonin (PCT) was a prespecified gated secondary marker. Results: The within-episode CRP coefficient was β = 0.1731 (95% CI 0.0259–0.3204; p = 0.0212), corresponding to 12.7% higher D-dimer per CRP doubling. The PCT coefficient was β = 0.0979 (95% CI 0.0037–0.1921; p = 0.0415). Point estimates remained positive across prespecified sensitivities, but confidence intervals crossed zero in fixed-effects, robust GEE, and complete-case analyses; only 49/100 episodes contributed an M3 CRP–D-dimer pair. Conclusions: In this small, incomplete secondary dataset, the findings provide limited, model-dependent evidence of positive same-assessment CRP–D-dimer covariation. They do not establish a definitive association, temporal coupling, causality, SIC/DIC, treatment response, prognosis, or clinical thresholds.