Extended Data Fig. 8: HMB-001 enhances fibrin dependent platelet aggregation at predicted plasma levels of FVIIa, total FVII(a) and HMB-001 following a once weekly HMB-001 dose of 0.67 mg/kg.
Fibrin-dependent platelet pseudoaggregation was measured in washed platelets from healthy donors supplemented with d-RGDW (GT-like; n = 3). The data in the bar chart are expressed as mean ± s.d. Aggregation was induced with collagen in buffer with 3 mM CaCl2+, 10 mg/mL FX, 20 ng/mL prothrombin and 0.5 mg/mL fibrinogen. The background plasma concentrations of FVIIa and total FVII(a) were assumed to be 67 pM and 10 nM, respectively. Predicted accumulated levels of total FVII(a) and FVIIa for once weekly HMB-001 dose of 0.67 mg/kg (scenario 3, Table S8) were reconstituted by adding FVII-S195A and FVIIa after accounting for the background plasma concentration of total FVII(a) and FVIIa respectively. HMB-001 was added as indicated. Light transmission was monitored for 60 min. Shown are representative light transmission aggregometry traces in a single donor, as well as summary data on fibrin-dependent pseudoaggregation lag time in all donors.