Nonclinical Evaluation of the New Topical Hemostatic Agent TT-173 for Skin Grafting Procedures.
Blood loss during grafting surgery represents a major concern of this procedure and the development of hemostatic agents for this indication is highly desirable. TT-173 is the first biologically active treatment based on tissue factor instead of thrombin. This study sought to investigate the efficacy, systemic absorption, and toxicology of TT-173 in animal models to support clinical evaluation of the product in donor sites of patients subjected to skin grafting. Procoagulant efficacy of 148 μg of TT-173 was evaluated in pigs in presence and absence of anticoagulant treatment with unfractioned heparin. Systemic absorption was quantified and characterized in rats subjected to severe skin lesions with affectation of muscular plane using TT-173 radiolabeled with I. The same animal model was used to test the toxicology of a dose of 80 μg of the product. Application of TT-173 significantly reduced the bleeding time of donor sites, even under anticoagulant treatment. Systemic absorption was low; it was excreted through urine and did not concentrate in organs such as liver, lung, or spleen suggesting that the absorbed dose could correspond to degradation fragments without procoagulant activity. Finally, a dose of 80 μg of TT-173 did not cause analytical disturbances suggestive of intravascular coagulation or any other adverse reaction. Nonclinical data obtained suggest that TT-173 could be useful to reduce the blood loss associated to burns treatment and support the clinical evaluation of the product in donor sites of patients subjected to skin grafting.
From the *Thombotargets Europe S.L. Mediterranean Technology Park, Castelldefels, Spain; †Unit of Human Anatomy and Embryology, Department of Morphological Sciences, Faculty of Medicine, Autonomous University of Barcelona, Cerdanyola del Vallès, Spain; ‡Molecular Imaging Research Group - Vall d'Hebron Research Institute, CIBBIM-Nanomedicine, Barcelona, Spain; §Unit of Experimental Surgery, Institute of Biomedical Investigation of A Coruña, A Coruña, Spain; and ‖Department of Plastic Surgery, University Hospital of A Coruña, A Coruña, Spain.
Santiago
S
Rojas Codina
José Raúl
JR
Herance
Alberto
A
Centeno
Javier
J
Valero
Belén
B
Arias
Ignasi
I
Miquel
Pilar
P
Sánchez
Esther
E
Rincón
Ramón
R
López
Jesús
J
Murat
D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport; D002056:Burns / Q000188:drug therapy* / Q000601:surgery*; D006489:Hemostatic Techniques; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D016038:Skin Transplantation / Q000379:methods*; D013552:Swine; D013917:Thrombin / Q000008:administration & dosage
D006490:Hemostatics; D013917:Thrombin