α(1,3)‐Fucosyltransferase‐IV deficiency contributes to a prothrombotic phenotype in mice

α(1,3)‐Fucosyltransferase‐IV (FUT4) and ‐VII (FUT7) synthesize functional selectin ligands including P‐selectin glycoprotein ligand‐1 (PSGL‐1). P‐selectin and PSGL‐1 interactions mediate processes that are prothrombotic. We examined whether FUT4 and/or FUT7 modulate thromboembolus formation in vivo. Thromboemboli were induced in mice lacking FUT4 and/or FUT7, or PSGL‐1, by tail vein administration of a collagen and epinephrine solution, and monitored by pulmonary thromboembolus‐induced mortality, and lung histology. Thromboembolus‐induced mortality was higher in mice deficient in FUT4, or both FUT4 and FUT7 (FUT4−/− = 82% mortality, n = 11, p = 0.002; FUT4−/−FUT7−/− = 78% mortality, n = 9, p = 0.003) than in WT mice (WT = 17% mortality, n = 12) or mice deficient in FUT7−/− (40% death, n = 10, p = 0.25). Histologic analysis showed a higher lung thromboembolus count (No; per cm 2 ) in FUT4−/− (No = 250; p = 0.009) and FUT4−/−FUT7−/− (No = 251; p = 0.007) mice relative to WT (No = 110) and FUT7−/− (No = 129; p = 0.67) mice. Thromboembolus‐induced mortality (PSGL‐1−/− = 60% mortality, n = 10; WT = 70% mortality, n =10; p = 0.5) and lung thromboembolus count (PSGL1−/− No =279; WT No = 341; p = 0.27) was not different between PSGL1−/− and WT mice. These data suggest that FUT4 deficiency contributes to a PSGL‐1‐independent prothrombotic phenotype. Support by RO1‐ HL090823 (JWH) and ES007017 (HW).