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 

  • 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

  • D-dimer test for VTE detection can be improved when cut-off values are calibrated with respect to the sex of the patient1

  • 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

  • Computed tomography, ventilation perfusion scanning or venous ultrasound were done to confirm VTE diagnosis1

  • 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

  • Youden threshold and 95% sensitivity cut-off values were calculated and tested for statistical significance1

  • 6% were diagnosed with PE in the suspected PE group while 11% were diagnosed with DVT in the suspected DVT group1

  • 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
(IQR) 

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
mg/L (95%CI)

95% Sensitivity Cut-off
mg/L(95%CI)
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

  • Confirmatory imaging was not performed in patients with negative D-dimer test thus these patients were not diagnosed with VTE based on follow-up1

  • Imaging of legs and lungs of patients was not performed to confirm if there is concurrence of PE and DVT1

  • Age was the only confounding covariate included in the analysis1

  • Unmeasured confounders such as comorbidities and drugs were not included in the multivariable linear regression analysis1

    *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

    1. 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

 

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