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

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).

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.

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.

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.