Pharmacopeia Potency Equated Sulodexide Produces Comparable Anticoagulation as Studied in Whole Blood

Introduction Sulodexide is a widely used glycosaminoglycan derived drug for oral (antithrombotic) and parenteral (anticoagulant) indications and is composed of fast moving heparin (80%) and dermatan sulfate (20%). In view of the current shortage of porcine heparin supply sulodexide may be a potential substitute for heparin for surgical and interventional anticoagulation. The purpose of this study is to compare the anticoagulant activities of sulodexide with heparin in simulated studies to mimic surgical and interventional anticoagulation. Materials and Methods Powder versions of sulodexide were obtained from Alfasigma (Bologna, Italy). Powder versions of porcine mucosal heparin were obtained from Medefil (Glendale Heights, IL, USA). Stock solution of both heparin and sulodexide were prepared in sterile saline at 10mg/ml. Sterile solutions were made at 1.0 and 0.1mg/ml. USP potency for both drugs were measured, cross referenced against US pharmacopiel standard and expressed as units per milligram. Whole blood activated clotting time was measured in healthy human volunteers at graded concentrations of both drugs. Plasma based anticoagulant assays such as activated partial thromboplastin time (APTT) and thrombin time (TT) were measured. Protamine neutralization studies were also carried out in the different assays used. Results The USP potency of sulodexide range from 90 – 105 U/mg whereas the porcine heparin exhibited a potency range of 180 – 200 U/mg as measured by the anti‐Xa activity. In the ACT assays USP potency adjusted sulodexide and heparin produced concentration dependent prolongation of this test which were comparable to heparin. Both the sulodexide and heparin produce concentration dependent anticoagulant effects in the APTT and TT assays. Protamine sulfate produced effective neutralization of the anticoagulant effects of both the sulodexide and heparin. Conclusions These results suggest that at USP potency equated levels sulodexide is capable of producing similar anticoagulant effects as unfractionated heparin. The USP potency of sulodexide can be adjusted at a comparable potency to porcine heparin to obtain comparable anticoagulant responses in the in vitro setting. Additional in vivo studies are warranted to compare the potency adjusted sulodexide with heparin.