Elevated D-dimer levels in high-risk multiple myeloma patients: a systematic review and meta-analysis.

BACKGROUND: Patients with multiple myeloma (MM) exhibit elevated thrombotic risk and variable disease outcomes. D-dimer, a fibrin degradation product, may serve as a biomarker reflecting both hypercoagulability and disease severity. This systematic review and meta-analysis compared D-dimer levels between MM patient subgroups defined by either poor prognostic features (e.g., advanced ISS stage) or thrombotic events and reference groups, with detailed discussion of how D-dimer integration reshapes routine thromboprophylaxis strategies and upgrades classic prognostic staging tools (ISS, R-ISS, IMPEDE-VTE). METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library from 2010 to 2025 for studies comparing plasma D-dimer levels between high-risk MM patients, defined by advanced ISS stage, occurrence of venous thromboembolism (VTE), or as a predictor of mortality, and reference groups. The primary outcome was the standardized mean difference (SMD) in D-dimer levels. Random-effects meta-analysis was performed using the inverse-variance method. Subgroup analyses examined differences by sample type and assay methodology. Risk of bias was assessed using domains adapted from ROBINS-I. RESULTS: Six studies comprising 697 patients (171 high-risk, 526 reference) met inclusion criteria. High-risk MM patients demonstrated significantly elevated D-dimer levels compared to reference groups (SMD 1.60, 95% CI 0.72-2.48, p<0.0001, I²=88.2%). The effect remained consistent across subgroup analyses by sample type (all plasma: SMD 1.60, 95% CI 0.72-2.48) and assay method (immunoturbidimetric: SMD 1.59, 95% CI 0.44-2.75; fluorescent immunoassay: SMD 1.64, 95% CI 0.78-2.49). Sensitivity analysis confirmed robustness of findings. Funnel plot asymmetry was minimal, although formal tests were not conducted given the limited number of studies. CONCLUSIONS: MM patients with poor prognostic features or who experience VTE exhibit substantially elevated D-dimer levels compared to lower-risk populations (SMD >1.5). Beyond confirming statistical significance, our results deliver actionable clinical insights: D-dimer supplementation optimizes risk stratification workflows built on ISS/R-ISS and refines personalized thromboprophylaxis regimens derived from the IMPEDE-VTE scoring model. D-dimer may serve as a useful biomarker for risk stratification in MM, though prospective validation studies are needed.