A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures.
OBJECTIVE
Recombinant thrombin (rThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. This report examines the clinical results for the vascular surgery subgroup of patients enrolled in a larger double-blind, randomized, multicenter trial, which evaluated the comparative safety and efficacy of rThrombin and bovine plasma-derived thrombin (bThrombin) when used as adjuncts to surgical hemostasis.


METHODS
Data from the 164 vascular patients who underwent either a peripheral arterial bypass (PAB) or arteriovenous graft (AV) procedure are included in this analysis. Time to hemostasis at proximal and distal anastomotic sites at 1.5-, 3-, 6-, and 10-minute intervals was determined by procedure (PAB or AV) and overall (PAB + AV). Baseline and day 29 immunologic sera were analyzed. The incidences of postoperative adverse events were compared between treatment groups. Categorical adverse events were evaluated in relation to thrombin product antibody formation.


RESULTS
Patients were randomized to either bThrombin (n = 82) or rThrombin (n = 82). Procedures included PAB (n = 88) and AV (n = 76). The bThrombin and rThrombin groups were well matched for demographics and baseline characteristics. A comparable incidence of anastomotic hemostasis was observed in both treatment groups at 10 minutes (94% bThrombin, 91% rThrombin). The incidence of hemostasis was lower at all time points for PAB procedures compared with AV procedures. In the PAB group, a significantly greater proportion of patients receiving rThrombin (55%) achieved hemostasis at 3 minutes compared with bThrombin (39%; P < .05). Adverse event profiles and laboratory findings were similar between groups. No patients in the rThrombin group developed anti-rThrombin product antibodies at day 29, whereas 27% of patients in the bThrombin group developed antibodies to bThrombin product (P < .0001).


CONCLUSIONS
rThrombin or bThrombin used as a hemostatic ancillary for anastomotic bleeding was equally effective at 10 minutes; however, rThrombin compared with bThrombin may provide a more rapid onset of hemostasis at 3 minutes in PAB procedures. Adverse events were similar between the two thrombins. In patients undergoing vascular surgery, both treatments were similarly well tolerated, although rThrombin demonstrated a superior immunogenicity profile.
Weaver
Fred A
FA
USC CardioVascular Thoracic Institute, Los Angeles, CA 90033-4612, USA. fweaver@surgery.usc.edu
Lew
Wesley
W
Granke
Kenneth
K
Yonehiro
Layne
L
Delange
Burke
B
Alexander
W Allan
WA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D002417:Cattle; D004311:Double-Blind Method; D005260:Female; D006488:Hemostasis, Surgical / Q000379:methods*; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000601:surgery*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D006490:Hemostatics; D011994:Recombinant Proteins; D013917:Thrombin