@entity3459 in XXXX by Non-Anticoagulant Sulfated Polysaccharides (NASP).

@entity1 @entity548 @entity447 @entity19 @entity11287 @entity3459 @entity11524 @entity4461 @entity2880 @entity4777
Additional therapeutic options are needed for @entity1 with @entity3459 such as @entity447 , @entity4777 , severe @entity2880 , and other rare factor deficiencies. A novel approach to improve coagulation in such @entity4461 has been identified that, parodoxically, involves heparinlike sulfated polysaccharides. Select molecules of this broad class are largely devoid of anticoagulant activity and are here denoted Non-Anticoagulant Sulfated Polysaccharides (NASPs). A mechanism involving blockade of the extrinsic pathway downregulator, @entity11524 ( @entity11524 ) by NASPs, was conceived as an approach for improving procoagulant behavior in hemophilic settings. A subset of NASPs, including pentosan polysulfate (PPS) and fucoidan inhibited both full-length and Kunitz 1 and 2 (K1K2) @entity11524 and, at concentrations from 4-500 nM, improved (i.e. accelerated) the clotting time of @entity1 @entity447 and @entity4777 plasmas or plasma with reduced factor VII levels when tested in dilute prothrombin time (dPT) assays. Fucoidan did not reduce normal plasma APTT times implying specificity for extrinsic pathway control. Improved hemostasis in vivo was observed in @entity19 with @entity447 A or B following low dose subcutaneous administration of @entity11287 or fucoidan, or a combination of NASP plus factor supplement. Increased survival of factor deficient @entity19 following a @entity548 challenge was observed. Accordingly, administration of select NASP(s), via mechanism(s) not fully understood, represents a unique means of improving coagulation in @entity3459 .
