Comparative study of the haemostatic effects of two antifibrinolytic agents during liver transplantation

Bleeding secondary to hyperfibrinolysis remains a subject ol' major concern during orthotopic liver transplantation (OLT) and has been controlled with variable success by antifibrinolytic agents. The aim of the present study is to compare the effect of two antifibrinolytic drugs, aprotinin and tranexamic acid, on blood loss, on the in vitro coagulation tests and on the markers of in vivo haemostatic and fibrinolytic systems during OLT. Thirty patients undergoing primary liver transplantation for liver cirrhosis have been randomly allocated in two groups treated either with aprotinin (group 1) or with tranexamic acid (group 2). The results obtained have been compared with a group of patients who did not receive antifibrinolytic drugs. Aprotinin was started during the anhepalic phase at a dosis of 16 millions protease inhibitor units (P1U) (Iniprol® institut Choay) injected in thirty minutes followed by a perfusion of 4 millions PIU per hour until the end of the procedure. Tranexamic acid (Exacyl® Institut Choay) was administrated at a dosis of 80 mg/kg during the first hour of the anhepatic phase followed by a dosis of 40 mg/kg/hour until the end of the surgery. Blood samples were collected before surgery, at the end of the dissection phase, at the end of the anhepatic phase and 5, 30, 6U, and 120 minutes after reperfusion of the grafted liver. The following analyses were performed on each sample: activated partial thromboplastin time (APTT), prothrombin time (PT), Thrombin time (TT), fibrinogen (Fg), platelet count (pit), thrombin-antithrombin complexes (TAT), prothrombin fragment 1+2 (Fl +2), plasmin-antiplasnun complexes (PAP) fibrinogen degradation products (fgdp) and fibrin degradation products (fbdp). No differences between mean blood loss was observed between the three groups {4588ml, 4692ml and 3950ml for the control, aprotinin and tranexamic acid groups,respectively). No marked variation of the PT, TT, Fg and pit was observed during the surgical procedure and the results were similar in the three groups of patients. On the other hand, APTT was markedly prolonged m the aprotinin group due to the contact phase inhibition properties of the drug. The results the highest mean value of the assay of the activation products of the hemostatic and the librinolytic systems are shown in the following table: Assay Aprotinin Tranexamic acid Control mean(sd) mean(sd) mean (sd) Fl-2(nmoll) 13.1(1.7) 7.6(0.8) 7.4(0.75) TAT (μg/1) 582(107) 343(67) 281 (40) PAP(μg/l) 2033(219) 2661(291) 14984(4778) Fgdp (μg/1) 9303 (3044) 1101 (253) 17586(9910) Fbdp(μg/l) 30599(13696) 5642(1257) 49017(24465) In conclusion, this study does not demonstrate any blood saving effect of antifibrinolytic drugs during liver transplantation. Tranexamic acid has a higher antifibrinolytic effect as compared with aprotinin, which is probabely related to the high dosis used. A lower in vivo activation of the coagulation system is observed with tranexamic acid, as compared with aprotinin, as evidenced by lower Fl-2 and TAT. If this observation is still observed for an equal anliiibrinolytic effect, this would suggest that tranexamic acid presents a lower thiombogenic potential than aprotinin.SCOPUS: ar.j