title: Recombinant human thrombin: in surgical hemostasis.
abstract: Recombinant human thrombin (rhThrombin) is a serine protease coagulant, manufactured in vitro using recombinant DNA technology, which shares an identical amino acid sequence and similar structure with the native human protein. It is indicated for topical use as an aid to hemostasis in patients undergoing surgery. Topical rhThrombin 1000 U/mL was no less effective than bovine thrombin (bThrombin) 1000 U/mL as a hemostatic agent in a randomized, double-blind, multicenter, phase III trial in patients undergoing various surgical procedures (n = 401). Hemostasis, achieved within 10 minutes, occurred in 95.4% of rhThrombin versus 95.1% of bThrombin recipients (primary endpoint) in the overall surgical cohort. Moreover, hemostasis occurred rapidly, with more than 70% of recipients of rhThrombin or bThrombin achieving hemostasis within 3 minutes. In a post hoc, subgroup analysis of this phase III trial, rhThrombin was also effective in patients undergoing vascular surgery, with hemostasis occurring within 10 minutes at >90% of all vascular anastomotic sites. Significantly fewer patients undergoing various surgical procedures were seropositive for antibodies against rhThrombin than bThrombin 1 month after topical hemostatic treatment in the phase III trial. In a noncomparative, multicenter, phase IIIb trial (n = 200), 1 month after vascular or spinal surgery where topical rhThrombin was used as a hemostat, the incidence of patients with evidence of anti-rhThrombin antibody formation was zero and did not differ between those classified as seropositive or seronegative for pre-existing anti-bThrombin antibodies at baseline (primary endpoint). rhThrombin was generally well tolerated during the treatment and 1-month follow-up periods in adult surgical patients, with a tolerability profile similar to that of bThrombin.
authors.affiliation: Adis, a Wolters Kluwer Business, Auckland, New Zealand. demail@adis.co.nz
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Croxtall
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Scott
mesh_terms: D000818:Animals; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin