Increased arterial and venous thrombosis but normal hemostasis in platelet XPR1-deficient mice. (A) Thrombus formation was induced in the left carotid artery by topical application of 5% FeCl3 for 3 minutes in F12−/−, Xpr1fl/fl, Xpr1fl/+ Pf4-Cre, and Xpr1fl/fl Pf4-Cre mice. Artery patency was monitored by a flow probe until complete occlusion occurred, and 0 flow was recorded for >10 minutes. Representative curves for 5 to 8 mice per genotype. (B) Time to complete carotid artery occlusion in the Xpr1fl/fl, Xpr1fl/fl Pf4-Cre, and Xpr1fl/+ Pf4-Cre mice from panel A. (C) PTE was induced by IV infusion of collagen and epinephrine in Xpr1fl/fl, Xpr1fl/fl Pf4-Cre, Xpr1fl/+ Pf4-Cre, and F12−/− mice. Shortly after the onset of respiratory arrest or at 30 minutes in mice that survived collagen-epinephrine treatment, Evans blue was infused IV while the heart was still beating. Occluded parts of the lungs remained their natural pinkish color. Lungs were excised, and perfusion defects were analyzed by impaired distribution of the dye in lung tissue (top), and survival time was assessed (bottom). Scale bar, 5 mm. (D) Hematoxylin and eosin–stained sections of lungs from Xpr1fl/fl, Xpr1fl/fl Pf4-Cre, Xpr1fl/+ Pf4-Cre, and F12−/− mice 30 minutes after collagen-epinephrine challenge (top). Green asterisks mark thrombi. Original magnification, ×10. The number of thrombi per visual field was counted in 6 mice (bottom). Data represent the mean ± standard deviation of 10 fields each. Scale bar, 100 µm. Bleeding times and blood loss from clipped tails assessed the hemostatic capacity of Xpr1fl/fl, Xpr1fl/fl Pf4-Cre, and Xpr1fl/+ Pf4-Cre mice. Bleeding time (E) and total hemoglobin loss (F), as determined by absorbance of hemoglobin in 37°C phosphate-buffered saline at λ = 575 nm. (G) Tail bleeding times were analyzed by gently adsorbing blood with a filter paper. Each symbol represents 1 animal; *P < .05; **P < .01; n.s. nonsignificant, by 1-way ANOVA and Tukey’s multiple comparison test.