Paired Analysis of D-Dimer and Its Correlated Hemostatic Parameters in 30 Dogs with Neoplasms after Tumorectomy

Abstract

Previous studies have reported that dogs with neoplasms had elevated D-dimer levels. However, few studies have addressed whether D-dimer could be an indicator of tumor burden. The clinical significance of paired analysis of pre- and post-operation of D-dimer levels in dogs has rarely been described. The present study investigated the values of D-dimer levels and their correlated hemostatic alterations in dogs with surgically removable benign and malignant tumors. This study analyzed 30 clinically healthy and 30 tumor-bearing dogs and evaluated the hemostatic functions including D-dimer, thromboelastography G (TEG G), fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time, and platelet count. The median level of pre-treatment D-dimer was 0.8 µg/mL (range: 0.1-6.3 µg/mL), whereas the control dogs exhibited a median value of 0.1 µg/mL (range: 0.1-0.1 µg/mL, p < 0.0001). After tumorectomy, the median levels of D-dimer (p < 0.0001), fibrinogen (p < 0.0001), TEG G value (p < 0.01), and aPTT (p < 0.05) were significantly lower than those of the pre-treatment samples. However, further studies are needed to clarify the values of other hemostatic evaluations. The study revealed the clinical significance of D-dimer and its correlated hemostatic parameters by paired analysis in dogs with tumors. Though more cases are needed for solid confirmation, these values could be potential tumor biomarkers for dogs.

Keywords: D-dimer; hemostatic parameter; liquid biopsy; tumor biomarker.

Figure 1

D-dimer concentrations in plasma of all dogs with neoplasms (n = 30) and control dogs (n = 30). (a) The median values of D-dimer in cancer and control dogs were 0.8 ± 3.15 and 0.1 ± 0.0 µg/mL, respectively (p < 0.0001); (b) The ROC curve of detection of D-dimer. The area under the ROC curve (AUC) is 0.90 under a 95% confidence interval of 0.8116–0.9884, with significant difference (p < 0.0001). ****, p < 0.0001.

Figure 2

Alteration of D-dimer concentrations in plasma of different types of tumor-bearing dogs before and after treatment. (a) The median values of D-dimer are 0.1, 0.8 ± 3.15, and 0.3 ± 1.85 µg/mL in control, pre-treatment, and post-treatment dogs, respectively. The D-dimer values significantly decreased after the operation in all the individuals with tumors (p < 0.0001) and the values were significantly elevated in dogs with tumors before (p < 0.0001) and after (p < 0.001) tumorectomy compared with the control dogs; (b) D-dimer significantly decreased in dogs suffering from mesenchymal (n = 14, p = 0.0039) and epithelial tumors (n = 12, p = 0.0039) after treatment. However, there are no obvious changes in the other dogs with neoplasms (n = 4, p = 0.25). Before treatment, the median values of D-dimer were 0.65 ± 3.23, 1.00 ± 2.95, and 2.25 ± 4.03 µg/mL in mesenchymal, epithelial, and melanoma tumor-bearing dogs, respectively. After treatment, the median values of D-dimer were 0.30 ± 2.00, 0.35 ± 1.48, and 1.15 ± 2.50 µg/mL in mesenchymal, epithelial, and melanoma tumor-bearing dogs, respectively. No statistical differences were found among these three populations before or after treatment (p > 0.05). p values < 0.05 were considered to indicate statistical significance. **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; n.s., no significant difference.

Figure 3

Differences of (a) TEG G, (b) fibrinogen, (c) aPPT, (d) PT, and (e) PLT before and after tumorectomy. The dotted lines represent the reference interval (TEG G: 3.2–7.2 × 10³ dyn/cm²; fibrinogen: 1–4 g/L; aPPT: 7–11.9 s; PT: < 8.5 s; PLT: 200–500 10⁹/L). Statistical analysis was performed using GraphPad Prism v9. To determine significant differences between before and after operation, the Wilcoxon matched-pairs signed-rank test was utilized and p values < 0.05 were considered as indicating statistical difference. Data are presented as median ± interquartile range. TEG G, thromboelastography G; aPPT, activated partial thromboplastin time; PT, prothrombin time; PLT, platelet count; *, p < 0.05; **, p < 0.01; ****, p < 0.0001; n.s., no significant difference.

Figure 3

Differences of (a) TEG G, (b) fibrinogen, (c) aPPT, (d) PT, and (e) PLT before and after tumorectomy. The dotted lines represent the reference interval (TEG G: 3.2–7.2 × 10³ dyn/cm²; fibrinogen: 1–4 g/L; aPPT: 7–11.9 s; PT: < 8.5 s; PLT: 200–500 10⁹/L). Statistical analysis was performed using GraphPad Prism v9. To determine significant differences between before and after operation, the Wilcoxon matched-pairs signed-rank test was utilized and p values < 0.05 were considered as indicating statistical difference. Data are presented as median ± interquartile range. TEG G, thromboelastography G; aPPT, activated partial thromboplastin time; PT, prothrombin time; PLT, platelet count; *, p < 0.05; **, p < 0.01; ****, p < 0.0001; n.s., no significant difference.