The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation

Abstract

It has been known for several decades that thromboelastographic analysis of the blood of patients undergoing liver transplantation may show a heparin-like effect (HLE) at the time of reperfusion. However, the prevalence of HLE and the origin of these heparin-like substances remain largely unstudied. The primary aim of this retrospective observational analysis was to determine the prevalence of the HLE in 211 consecutive patients having liver transplantation in our institution at various stages throughout the transplant. One of the secondary aims was to analyze the prevalence of HLE with respect to the various etiologies of liver disease. Paired Thromboelastograph traces (native and heparinase) were examined at 5 stages of the transplant: the baseline stage, dissection stage, anhepatic stage, reperfusion stage, and end of the case. HLE was defined as a reduction in the reaction and coagulation times of greater than 50% by the addition of heparinase to the sample. Thirty-one percent of patients had evidence of an HLE at baseline, and this increased to 75% after reperfusion of the donor graft. This HLE resolved spontaneously in 47% by the end of the case. Patients with fulminant liver failure were more likely to demonstrate HLE at baseline than those with chronic liver disease (45.8% compared to 29%). There was no difference in the prevalence of HLE after reperfusion. In conclusion, prior to transplantation, there is a significant difference in the prevalence of HLE with respect to etiology. However, this difference disappears after reperfusion as the majority of patients then develop HLE. Although it is clear that there are both endogenous and exogenous sources of heparin contributing to the HLE, the clinical significance of these findings remains unclear. Liver Transpl 14: [855][856][857][858][859][860] 2008 The Thromboelastograph (TEG) was first used during orthotopic liver transplantation by Kang et al. 1 in the 1980s as a bedside monitor of coagulation, and it is a standard guide to transfusion of various blood components in many transplant centers. 2 Typical changes seen in TEG on reperfusion of the graft liver include a lengthening of the reaction time (R time) and coagulation time (K time), a diminished maximum amplitude, and an increase in fibrinolysis. 2 This phenomenon is partly explained by the heparin-like effect (HLE) because even a small amount of heparin in the circulation prolongs R time and, in some cases, K time. 3,4 An HLE seen on TEG was first described during human liver transplantation in 1985 by Kang et al. 1 It was noted that the HLE corrected in vitro with protamine administration 1 and resolved spontaneously in most patients within 1 to 2 hours without any treatment. The use of heparinase-modified TEG began in the 1990s. In 1997, Harding and colleagues demonstrated that the addition of heparinase I, an enzyme-neutralizing heparin, heparan sulfate, and dermatan sulfate 5 to whole blood samples in vitro normalizes the TEG indicating the presence of one of these substances 6 (Fig. 1). This ...

Thromboelastometric Profile in Patients with Prothrombotic Risk Factors Undergoing Liver Transplantation

“…In this study, CT enlargement in the INTEM after reperfusion was represented in more than 53% of the patients due to the effect of heparin, in agreement with the study of Agarwal et al [35] where they demonstrated in a retrospective and observational study of 211 patients undergoing liver transplantation that the prevalence of heparin was demonstrated in more than 80% of cases after reperfusion of the graft.…”

Reducing transfusion requirements in liver transplantation

“…This may be more pronounced with marginal grafts from DCD donors and with significant hepatic-ischaemic-reperfusion insult [46] . The clinical significance of the HLE is not fully understood but it usually resolves spontaneously by the end of the case in the context of a good functioning graft [47] . Hyperfibrinolysis is common due to an increase in tPA from the new liver and decreased production of antifibrinolytic factors and may be associated with increased bleeding [48] .…”

Monitoring of haemostasis in liver transplantation: comparison of laboratory based and point of care tests

“…Coagulation abnormalities during orthotopic liver transplanation are characterised by decreased coagulation factors, antifibrinolytic factors and endogeneous anticoagulant factors [1], all of which represent a major perioperative challenge as both bleeding episodes and thrombotic events can be precipitated [2,3]. Accordingly, monitoring of the coagulation system during liver transplantation is important.Besides standard laboratory methods, point of care assays are gaining increasing acceptance since their results are rapidly available [4][5][6][7][8]. However, only sparse information is available on the comparability of point of care coagulation assays with laboratory coagulation assays in this special setting.…”

“…Besides standard laboratory methods, point of care assays are gaining increasing acceptance since their results are rapidly available [4][5][6][7][8]. However, only sparse information is available on the comparability of point of care coagulation assays with laboratory coagulation assays in this special setting.…”