Acad Emerg Med. 2021 Jan 26. doi: 10.1111/acem.14220. Online ahead of print.
BACKGROUND: D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized the accuracy of D-dimer tests may be enhanced by using appropriate cut-off values that reflect sex-related differences in D-dimer levels.
METHODS: This research is a secondary analysis of a multi-center, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pre-test probability based on Wells criteria ≤ 6 for PE and ≤ 2 for DVT. VTE diagnoses were based on computed tomography, ventilation perfusion scanning or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from ROC analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cut-off corresponding to 95%-sensitivity were calculated. Statistical difference for cut-offs was tested via 95% confidence intervals from 2000 bootstrapped samples.
RESULTS: We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% white, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE positive group and the DVT negative group, but males had significantly lower D-dimer levels than females in the PE negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden threshold for PE patients were 0.97 mg/L (95% CI 0.64-1.79) and 1.45 (95% CI 1.36-1.95) for females and males, respectively; 95%-sensitivity cut-offs for this group were 0.64 (95% CI 0.20-0.89) and 0.55 (95% CI 0.29-1.61). For DVT, the Youden thresholds were 0.98 mg/L (95% CI 0.84-1.56) for females and 1.25 (95% CI 0.65-3.33) for males with 95%-sensitivity cut-offs of 0.33 (95% CI 0.2-0.61) and 0.32 (95% CI 0.18-0.7), respectively.
CONCLUSION: Differences in D-dimer levels between males and females are diagnosis specific, however there was no significant difference in optimal cut-off values for excluding PE and DVT between the sexes.