A proposed model of action for DNase I, recombinant ADAMTS13, and caplacizumab to inhibit NET and thrombus formation under flow. (A) Under flow, VWF is released from endothelial cells (EC) upon stimulation and remains anchored on the endothelial surface, which captures flowing platelets and neutrophils. Neutrophils undergo NETosis and release histone-DNA and histone-MPO complexes (NETs) that bind to VWF and activate platelets to enhance thrombus formation. (B) Whether extracellular DNA strings are degraded by DNase I, VWF strings are removed by rA13, or platelet-VWF interactions are inhibited by Capla or ANF, the result is to destabilize the thrombus structure, dampening inflammation, and thrombosis under flow. ANF, anfibatide; Capla, caplacizumab; EC, endothelial cell; N, neutrophil; PLT, platelet; rA13, recombinant ADAMTS13.