Recombinant Thrombin: Safety and Immunogenicity in Burn Wound Excision and Grafting

• Published in: Journal of burn care & research Vol. 30; no. 3; pp. 371 - 379
• Main Authors: GREENHALGH, David G, GAMELLI, Richard L, COLLINS, Jay, SOOD, Rajiv, MOZINGO, David W, GRAY, Todd E, ALEXANDER, W. Allan
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott Williams & Wilkins 01-05-2009
• Subjects: Administration, Topical; Adolescent; Adult; Aged; Biological and medical sciences; Burns; Burns - therapy; Child; Dermatology; Female; Graft Survival; Hemostatics - administration & dosage; Hemostatics - immunology; Hemostatics - therapeutic use; Humans; Male; Medical sciences; Middle Aged; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; Safety; Skin Transplantation - adverse effects; Thrombin - administration & dosage; Thrombin - immunology; Thrombin - therapeutic use; Traumas. Diseases due to physical agents; Treatment Outcome; Wound Healing - physiology; Burn; Peptidases; Skin disease; Serine endopeptidases; Immunogenicity; Enzyme; Hydrolases; Thrombin; Wound
• ISSN: 1559-047X; 1559-0488
• DOI: 10.1097/BCR.0b013e3181a28979

This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients undergoing skin grafting for burns. This was a phase 2 multiple site, single-arm, open-label study in patients receiving partial- or full-thickness autologous grafts. rThrombin was applied using a spray applicator to newly excised wounds of 1 to 4% body surface area at 5 minutes intervals for up to 20 minutes, after point source bleeding was stopped. Adverse events, skin graft survival, and formation of anti-rThrombin antibodies were measured at baseline and Day 29. There were no deaths or study drug discontinuations. Adverse events occurred in 63 of 72 patients (88%), and were typical of sequelae of skin grafting. Hemostasis was achieved within 20 minutes after application of rThrombin in 65 of 71 patients (91.5%). Skin graft failure occurred in 4 patients (6%). At the day 29 evaluation, for those patients who returned, 88.9% had > or =90% graft survival. One patient (1 of 70, 1.4%) had specific, low titer antibodies to rThrombin at baseline, but no increase in titer posttreatment; a second patient (1 of 62, 1.6%), developed antibodies to rThrombin at day 29. None of the antibodies neutralized native human thrombin. In excised burn wounds, hemostasis at 20 minutes was achieved in 91.5% of patients and skin graft survival was excellent. There was a low rate of antibodies to rThrombin at baseline (1.4%) and a low rate of anti-rThrombin antibody formation at day 29 (1.6%). rThrombin was well tolerated when administered with a pump spray.