Cross-species rescue of fibrin deposition in f8^–/–;at3^–/– larvae by FVIII and VWF. (A) Model demonstrating the effect of FVIII levels on fibrin deposition. (B) f8^–/–;at3^–/– zebrafish larvae were injected with various combinations of plasmids encoding human (h) and zebrafish (z) FVIII and VWF and analyzed for fibrin deposition at 5 dpf by an observer blinded to condition. Injection groups included: uninjected controls, hVWF, hF8, zvwf, zf8, coinjection of hVWF + hF8, coinjection of zvwf + zf8, and cross-species combinations (hVWF + zf8 and zvwf + hF8). (C) Comparison of various groups shows that hVWF, but not zvwf, enhances fibrin deposition in combination with human or fish FVIII. Statistical analysis was performed using ordinal logistic regression followed by Dunnett's adjustments. (∗P < .05, ∗∗P < .01, ∗∗∗P < .001). ns, nonsignificant.