An analysis on the difference of D-dimer levels between males and females for VTE screening1

- There is a signifficant difference in D-dimer levels between males and females specific to VTE diagnosis suggesting that sex may be relevant in D-dimer level interpretation for VTE screening1
- There were no significant differences in optimal deep vein thrombosis (DVT) and pulmonary embolism (PE) D-dimer cut-off values between the sexes1

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Under several controlled factors, women were shown to have higher D-dimer levels among patients with a positive D-dimer (> 0.5 mg/L) or patients who are highly likely to have VTE1
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D-dimer test for VTE detection can be improved when cut-off values are calibrated with respect to the sex of the patient1

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This study conducted a secondary analysis of a multi-center, international, prospective, observational study of 3,586 adult patients suspected for VTE with low to intermediate risk of VTE according to Wells criteria: s ≤ 6 for PE and ≤ 2 for DVT1
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Computed tomography, ventilation perfusion scanning or venous ultrasound were done to confirm VTE diagnosis1
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Multivariable regression was performed to determine if sex is a predictor of diagnosis and statistical difference across groups stratified by sex and diagnosis was observed1
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Youden threshold and 95% sensitivity cut-off values were calculated and tested for statistical significance1

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6% were diagnosed with PE in the suspected PE group while 11% were diagnosed with DVT in the suspected DVT group1
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Significantly higher D-dimer levels were observed in males than females in PE-positive patients and DVT-negative group but lower D-dimer levels were seen in males than females in PE-negative group1
VTE assessment |
Sex |
Median D-dimer |
Adjusted P-value |
PE negative | Female (n=1103) Male (n=623) |
0.46 (0.28-0.94) 0.40 (0.22-0.82) |
<0.001* |
PE positive | Female (n=55) Male (n=53) |
3.32 (1.32-6.46) 4.67 (2.27-10.2) |
0.045* |
DVT negative | Female (n=959) Male (n=602) |
0.50 (0.29-0.99) 0.59 (0.29-1.28) |
<0.001+ |
DVT positive | Female (n=83) Male (n=108) |
2.40 (1.15-4.60) 3.33 (0.99-7.88) |
0.870+ |
Adapted from Reagh JJ, et al. 2021
- DVT and PE cut-off values for VTE screening were different between males and females but they were not statistically significant1
VTE assessment |
Sex |
Youden threshold |
95% Sensitivity Cut-off |
PE | Female (n=1,158) Male (n=676) |
0.97 (0.64-1.79) 1.45 (1.36-1.95) |
0.64 (0.20- 0.89) 0.55 (0.29-1.61) |
DVT | Female (n=1,042) Male (n=710) |
0.80 (0.84-1.56) 1 .25 (0.65-3.33) |
00.33 (0.20- 0.61) 0.32 (0.18- 0.70) |
- Male sex (AOR = 1.64 [95% Cl = 1.17 to 2.30]) and log D-dimer level (AOR = 3.10 [95% Cl = 2.65 to 3.63]) were found to be a significant positive predictor for positive DVT diagnosis1
- Age (AOR = 1.01 [95% Cl = 1.0 0 to 1.03]) and log D-dimer level (AOR = 4.43 [95% Cl = 3.54 to 5.53]) were found to be a significant positive predictor for positive PE diagnosis1

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Confirmatory imaging was not performed in patients with negative D-dimer test thus these patients were not diagnosed with VTE based on follow-up1
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Imaging of legs and lungs of patients was not performed to confirm if there is concurrence of PE and DVT1
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Age was the only confounding covariate included in the analysis1
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Unmeasured confounders such as comorbidities and drugs were not included in the multivariable linear regression analysis1
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Reagh JJ, Zheng H, Stolz U, et al. Sex-related differences in D-dimer levels for venous thromboembolism screening. Acad Emerg Med. 2021 Jan 26. doi: 10.1111/acem.14220
*Adjusted for age, race, cancer, mobility
+Adjusted for age, race, cancer, mobility, bedridden status, and past DVT history
VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; Cl, confidence interval; IQR, interquartile range; AOR, adjusted odds ratio
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