Figure 6.
Figure 6. Vitamin K antagonism leads to reduction of human leukocytes and engraftment of human HSC. (A) Percentage of human CD45+ leukocytes in the peripheral blood of vehicle-treated (red circles) or warfarin-treated (blue squares) NSG mice 6 weeks after transplantation with 1.3 × 105 human CD34+ HSC (P = .015, t test, n = 9). (B) Percentage of human CD45+ leukocytes in the peripheral blood of NSG mice 4 weeks after intrafemoral co-transplantation of 105 human CD34+ HSC and 5 × 105 vehicle-treated (red circles) or warfarin-treated (blue squares) human macrophages (P = .046; t test, n = 6). (C-F) Total number of leukocytes (P < .001; Wilcoxon test with Bonferroni correction) (C), monocytes (P = .006; Wilcoxon test with Bonferroni correction) (D), eosinophils (P = .002; Wilcoxon test with Bonferroni correction) (E), and basophils (P < .001; Wilcoxon test with Bonferroni correction) (F) in the peripheral blood of control patients (red) or patients receiving warfarin (blue; n = 131). The data in panels C-F are matched for sex and age. (G) Total number of monocytes (P = .04; Wilcoxon test with Bonferroni correction) in the peripheral blood of control patients (red) and patients receiving fluindione (blue; n = 109), another vitamin K-antagonist similar to warfarin. The controls in panel G are the same as in panels C-F, but matched to fluindione patients for sex and age. (H-I) Use of VKAs in men and women aged 70 to 79 years (n = 5 464 258) (H) or 50 to 60 years (n = 11 452,848) (I) with and without a diagnosis of MDS in 2015. Data source: French health-care databases.

Vitamin K antagonism leads to reduction of human leukocytes and engraftment of human HSC. (A) Percentage of human CD45+ leukocytes in the peripheral blood of vehicle-treated (red circles) or warfarin-treated (blue squares) NSG mice 6 weeks after transplantation with 1.3 × 105 human CD34+ HSC (P = .015, t test, n = 9). (B) Percentage of human CD45+ leukocytes in the peripheral blood of NSG mice 4 weeks after intrafemoral co-transplantation of 105 human CD34+ HSC and 5 × 105 vehicle-treated (red circles) or warfarin-treated (blue squares) human macrophages (P = .046; t test, n = 6). (C-F) Total number of leukocytes (P < .001; Wilcoxon test with Bonferroni correction) (C), monocytes (P = .006; Wilcoxon test with Bonferroni correction) (D), eosinophils (P = .002; Wilcoxon test with Bonferroni correction) (E), and basophils (P < .001; Wilcoxon test with Bonferroni correction) (F) in the peripheral blood of control patients (red) or patients receiving warfarin (blue; n = 131). The data in panels C-F are matched for sex and age. (G) Total number of monocytes (P = .04; Wilcoxon test with Bonferroni correction) in the peripheral blood of control patients (red) and patients receiving fluindione (blue; n = 109), another vitamin K-antagonist similar to warfarin. The controls in panel G are the same as in panels C-F, but matched to fluindione patients for sex and age. (H-I) Use of VKAs in men and women aged 70 to 79 years (n = 5 464 258) (H) or 50 to 60 years (n = 11 452,848) (I) with and without a diagnosis of MDS in 2015. Data source: French health-care databases.

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