Gabexate mesilate and antithrombin III for intraoperative anticoagulation in heparin pretreated patients

Abstract

Thirty patients scheduled for elective myocardial revascularization and having undergone preoperative heparin treatment have been admitted to this prospective, randomized study. The aim of the study was to test two different strategies for preserving circulating antithrombin III (AT-III) during cardiopulmonary bypass. Patients in the control group (group C, n = 10) were treated with a standard heparinization (300 IU/kg). Patients in group A (n = 10) received the same management plus two doses of purified antithrombin III (1000 IU each). Patients in group GA received 200 IU/kg heparin and a continuous infusion of heparin (100 IU/kg/h) and gabexate mesilate (2 mg/kg/h) plus the same dose of antithrombin III as group A. Both group A and group GA demonstrated a preservation of circulating AT-III when compared to group C; this effect was more pronounced in group GA. The total heparin dosage was less in group GA than in groups A and C. Purified AT-III administration is recommended in heparin pretreated patients; the addition of gabexate mesilate to this protocol decreases the heparin requirement and increases the AT-III preservation.

Get full access to this article

View all access options for this article.

References

Esposito RA , Culliford AT , Colvin SB , Thomas SJ , Lackner H , Spencer FC. Heparin resistance during cardiopulmonary bypass. The role of heparin pretreatment . J Thorac Cardiovasc Surg 1983; 85: 346-353 .

Cloyd GM , D’Ambra MN , Akins CW. Diminished anticoagulant response to heparin in patients undergoing coronary artery bypass grafting . J Thorac Cardiovasc Surg 1987; 94: 535-538 .

Dietrich W , Spannagl M , Schramm W , Vogt W , Barankay A , Richter JA. The influence of preoperative anticoagulation on heparin response during cardiopulmonary bypass . J Thorac Cardiovasc Surg 1991; 102: 505-514 .

Marchiniak E , Gockerman JP. Heparin induced decrease in circulatory antithrombin III . Lancet 1977; 2: 581-584 .

Conard J , LeCompte T , Horellon MH , Cazenave B , Sanama M. AT III in patients treated with subcutaneous or intravenous heparin . Thromb Res 1981; 22: 507-511 .

Sabbagh AH , Chung GKT , Shuttleworth P , Applegate BJ , Gabrhel W. Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass . Ann Thorac Surg 1984; 37: 466-468 .

Hashimoto K , Yamagishi M , Sasaki T , Nakano M , Kurosawa H. Heparin and antithrombin III levels during cardiopulmonary bypass: correlation with subclinical plasma coagulation . Ann Thorac Surg 1994; 58: 799-805 .

Oedekoven B , Bey R , Mottaghy K , Schmid-Schönbein H. Gabexate mesilate (Foy®) as an anticoagulant in extracorporeal circulation in dogs and sheep . Thromb Haemost 1984; 52: 329-332 .

Denson KE. The ratio of Factor VIII-related antigen and factor VIII biological activity as an index of hypercoagulability and intravascular clotting . Thromb Res 1977; 10: 107-119 .

10.

Parodi F , Cordero G , De Gasperis C , Minola P , Dellora C , Innocenti P. Gabexate mesilate, a new synthetic serine protease inhibitor: a pilot clinical trial in valvular heart surgery . J Cardiothorac Vasc Anesth 1996; 10: 235-237 .

11.

Ranucci M , Albano G , Casalino S et al.

Nafamostat mesilate: in vitro study of its anti-proteasic properties: a new anticoagulant for cardiopulmonary bypass?

Cah CECEC 1993; 40: 93-101 .

12.

Schlag G , Redl H. The proteinases in shock . Resuscitation 1986; 14: 3-21 .

13.

Novelli GP , Innocenti P , Livi P. Il gabesato mesilato (FOY), nuovo antiproteasico sintetico, nel trattamento dello shock. Studio multicentrico italiano . Minerva Anestesiol 1993; 58: 247-253 .