Figure 2
Figure 2. FXIa inhibits the anticoagulant role of TFPI in plasma. (A) Clotting times were measured for recalcified plasma after addition of TF (Innovin) or/and an aPTT reagent in the presence of increasing concentrations of rTFPI. (B) TF-induced clotting times were measured in recalcified plasma in the presence of an aPTT reagent and increasing concentrations of rTFPI. Plasma was pretreated with vehicle (♦), 20 µg/mL 1A6 (○), 50 µg/mL 10C9 (◱), or 50 µg/mL 12F5 (△). Selected experiments were performed in FXI-depleted plasma (FXI-dep) (♢). (C) TF-induced clotting times were measured in FXI-deficient plasma in the presence of vehicle (white bars) or 2 nM rTFPI (black bars). In selected experiments, FXIa (5 nM) was added to plasma in the presence of vehicle or 20 µg/mL 1A6, 50 µg/mL 10C9, or 50 µg/mL 12F5. *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to vehicle in the presence of rTFPI and FXIa. (D) TF-induced clotting times were measured in FIX-deficient plasma in the presence of vehicle (white bars) or 2 nM rTFPI (black bars). Selected experiments were performed in the presence of an aPTT reagent and/or 20 µg/mL 14E11. *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to vehicle in the presence of rTFPI and aPTT reagent. (E) TF-induced clotting times were measured in normal plasma, FIX-depleted plasma, or FXI-depleted plasma in the presence of vehicle or 2 nM rTFPI. Selected experiments were performed in the presence of blocking anti-TFPI K1 and K2 antibodies (10 µg/mL). *P < .05 with respect to vehicle in the presence of rTFPI. (F) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle or 5 nM rTFPI pretreated with 1.25, 2.5, or 5 nM FXIa for 5 minutes. (G) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle or 5 nM rTFPI pretreated with 1 nM FXIa for 5, 30, or 60 minutes. *P < .05 with respect to vehicle in the presence of rTFPI. (H) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle (white bars) or 5 nM rTFPI (black bars). Experiments were performed in the presence of 5 nM FXIa pretreated with 20 µg/mL 1A6. Selected experiments were performed in the presence of blocking anti-TFPI K1 and K2 antibodies (10 µg/mL) or 50 µg/mL 10C9. Data are mean ± standard error (n = 3). *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to FXIa in the presence of rTFPI. Mann-Whitney U test was used for statistical comparisons.

FXIa inhibits the anticoagulant role of TFPI in plasma. (A) Clotting times were measured for recalcified plasma after addition of TF (Innovin) or/and an aPTT reagent in the presence of increasing concentrations of rTFPI. (B) TF-induced clotting times were measured in recalcified plasma in the presence of an aPTT reagent and increasing concentrations of rTFPI. Plasma was pretreated with vehicle (♦), 20 µg/mL 1A6 (○), 50 µg/mL 10C9 (◱), or 50 µg/mL 12F5 (△). Selected experiments were performed in FXI-depleted plasma (FXI-dep) (♢). (C) TF-induced clotting times were measured in FXI-deficient plasma in the presence of vehicle (white bars) or 2 nM rTFPI (black bars). In selected experiments, FXIa (5 nM) was added to plasma in the presence of vehicle or 20 µg/mL 1A6, 50 µg/mL 10C9, or 50 µg/mL 12F5. *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to vehicle in the presence of rTFPI and FXIa. (D) TF-induced clotting times were measured in FIX-deficient plasma in the presence of vehicle (white bars) or 2 nM rTFPI (black bars). Selected experiments were performed in the presence of an aPTT reagent and/or 20 µg/mL 14E11. *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to vehicle in the presence of rTFPI and aPTT reagent. (E) TF-induced clotting times were measured in normal plasma, FIX-depleted plasma, or FXI-depleted plasma in the presence of vehicle or 2 nM rTFPI. Selected experiments were performed in the presence of blocking anti-TFPI K1 and K2 antibodies (10 µg/mL). *P < .05 with respect to vehicle in the presence of rTFPI. (F) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle or 5 nM rTFPI pretreated with 1.25, 2.5, or 5 nM FXIa for 5 minutes. (G) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle or 5 nM rTFPI pretreated with 1 nM FXIa for 5, 30, or 60 minutes. *P < .05 with respect to vehicle in the presence of rTFPI. (H) FXa (0.5 nM)-induced clotting time was measured in FX-depleted plasma in the presence of vehicle (white bars) or 5 nM rTFPI (black bars). Experiments were performed in the presence of 5 nM FXIa pretreated with 20 µg/mL 1A6. Selected experiments were performed in the presence of blocking anti-TFPI K1 and K2 antibodies (10 µg/mL) or 50 µg/mL 10C9. Data are mean ± standard error (n = 3). *P < .05 with respect to vehicle in the presence of rTFPI. **P < .05 with respect to FXIa in the presence of rTFPI. Mann-Whitney U test was used for statistical comparisons.

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