title: Comparative anticoagulant and platelet modulatory effects of enoxaparin and sulodexide.
abstract: Sulodexide represents a novel antithrombotic agent with multiple sites of action on blood coagulation and vascular processes. The purpose of this study was to compare sulodexide and enoxaparin on anticoagulant effects, tissue factor (TF)-induced activation of platelets, inhibition of microparticle generation and to investigate their effect on heparin-induced platelet aggregation (HIPA). Sulodexide was compared with enoxaparin at equigravimetric concentrations. When compared to enoxaparin, sulodexide produced a stronger anticoagulant effect in the prothrombin time (PT), activated partial thromboplastin time (APTT), Heptest, and thrombin time (TT) assays. In addition, sulodexide had a stronger inhibitory effect on TF-mediated microparticle generation (IC(50) = 2.8 microg/ mL), P-selectin expression (IC(50) = 4.8 microg/ml), and platelet aggregate formation (IC(50) = 8.5 microg/mL) compared to higher IC(50) values with enoxaparin. Sulodexide and enoxaparin exhibited a similar effect on heparin-induced thrombocytopenia (HIT) antibody-mediated platelet activation HIPA assays. These results suggest that sulodexide is a relatively stronger anticoagulant agent than enoxaparin. Sulodexide is subcutaneously absorbed. Its ability to inhibit TF-mediated platelet activation may contribute to the observed therapeutic effects of sulodexide in microvascular vasculopathy such as diabetic nephropathy. These results also suggest that inhibition of TF activation of platelets by sulodexide may be independent of its anticoagulant effects. These results warrant further investigation of sulodexide in additional preclinical and clinical studies.
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: Cafer
authors.initials: C
authors.lastname: Adiguzel
authors.forename: Omer
authors.initials: O
authors.lastname: Iqbal
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: Walter
authors.initials: W
authors.lastname: Jeske
authors.forename: Josephine
authors.initials: J
authors.lastname: Cunanan
authors.forename: Evangelos
authors.initials: E
authors.lastname: Litinas
authors.lastname: He Zhu
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Walenga
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D017984:Enoxaparin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006025:Glycosaminoglycans; C007858:glucuronyl glucosamine glycan sulfate