Increased Tissue–Type Plasminogen Activator Activity in Orthotopic But Not Heterotopic Liver Transplantation: the Role of the Anhepatic Period

Abstract

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.

Intracardiac thrombus formation and pulmonary thromboembolism immediately after graft reperfusion in 7 patients undergoing liver transplantation

“…11,12 Activation of the fibrinolytic system during the anhepatic stage and especially after graft reperfusion is reflected by significant increases in tPA levels, which results from both impaired hepatic clearance of tPA and increased tPA release from vascular endothelium caused by trauma to mesenteric vessels, tissue injury, and hypothermia. [13][14][15][16][17] In addition, tPA is released by the graft, possibly related to ischemic damage of its endothelial cells. 13,14 The intrinsic coagulation system is also activated during OLT, especially during the anhepatic stage and after graft reperfusion.…”

Coagulation and Fibrinolysis in Orthotopic Liver Transplantation: Current Views and Insights

“…Hyperfibrinolysis is at least partly caused by an increase in t-PA, which is most likely due to primary activation and not secondary to clotting activation or DIC. 28,30 This knowledge gives scientific support for treatment with antifibrinolytic agents in an attempt to reduce blood loss and the usage of blood products. Recently, several groups have reported on the use of such agents, especially epsilon-aminocaproic acid (EACA) 13 and aprotinin (Trasylol), in OLT.…”

Haemostatic disorders during liver transplantation

“…Though no elevated tissue plasminogen activator activity has been observed in ®rst hepatic graft venous out¯ow by others [9], the latter factor may be important in some situations. Though no elevated tissue plasminogen activator activity has been observed in ®rst hepatic graft venous out¯ow by others [9], the latter factor may be important in some situations.…”

“…An extracorporeal venovenous bypass may be used to reduce splanchnic blood pooling and circulatory disturbances associated with cross-clamping of the inferior vena cava. In the latter situation, where a minimal hepatic function is maintained, tissue plasminogen activator activity levels remain within the normal range throughout the procedure [9]. Coagulation and ®brinolysis activation.…”