Assessment of haemostasis in patients with liver cirrhosis

Editor, We read with great interest the study by Lentschener et al.1 about the assessment of haemostasis in patients with cirrhosis and the relevance of the ROTEM test (TEM International, München, Germany). The authors compared the indices of ROTEM (maximum clot firmness values of EXTEM, INTEM and FIBTEM), thrombin generation and coagulation factors/inhibitors in stable cirrhotic patients. They found that ROTEM maximum clot firmness values ranged from normal to hypocoagulation status; the values directly correlated with factor V, serum fibrinogen, protein C, protein S and antithrombin III and inversely correlated with the model for end-stage liver disease scores. The Von Willebrand factor was above the normal level in all the stable cirrhotic patients. When adding the thrombomodulin thrombin generation test, thrombin generation potential was within or above normal values. Their finding that cirrhotic patients have a somewhat increased thrombin generation capacity is nothing new and follows the concept of ‘re-balanced haemostasis’ in cirrhotic patients as described by Lisman and associates2 in 2010. The findings that adding thrombomodulin to platelet-poor plasma enhances the thrombin generation potential has already been published by Tripodi et al.;3 they also compared the platelet-poor plasma of clinically stable cirrhotic patients with that of healthy volunteers. Under normal conditions, volunteers had significantly better thrombin generation potential than the cirrhotic patients; however, after adding thrombomodulin, this difference disappeared because of the activation of the coagulation inhibitors protein C and protein S. Lentschener and colleagues,1 in their study, did not show haemostatic functional contribution from platelets. The assessment of isolated thrombin generation without considering the impact of platelets in the whole blood is not suitable to determine the hypo- or hypercoagulopathic status of cirrhotic patients. Based on the result of ROTEM maximum clot firmness values, the authors stated that hypercoagulable values of ROTEM maximum clot firmness may encourage fresh frozen plasma transfusion. We disagree with the implications of this statement. Maximum clot firmness reflects clot stability and is determined by fibrinogen and platelets.4 Improvement of fibrinogen serum levels with fresh frozen plasma is not very effective.5 Therefore, lower values of ROTEM maximum clot firmness are not an indication for fresh frozen plasma transfusion. Fresh frozen plasma is used to accelerate the initiation of the coagulation process. However, to answer this question, it would have been more appropriate to evaluate the clotting time of ROTEM. This parameter was completely overlooked in their study. As a point-of-care viscoelastic whole blood coagulation monitoring system, ROTEM identifies reduced clot firmness, discriminates between fibrin polymerisation disorders and platelet dysfunction, identifies heparin/heparinoid effects and identifies deficiency of vitamin K-dependent coagulation factors.5 These are the major differences between ROTEM and thrombin generation potential. Thrombin generation potential only assesses the procoagulant/anticoagulant factors in plasma without incorporating the impact of platelets. Furthermore, the implication of the authors’ statement referred to the clinical practice of ROTEM-guided haemostatic treatment in liver transplantation. This should be read with great caution. First of all, it is not necessary or even detrimental to treat or pretreat the ‘abnormal coagulation values’ of cirrhotic patients undergoing liver transplantation without evidence of bleeding. ROTEM values are no exception to this principle.4 Secondary, the median maximum clot firmness in EXTEM was 53 mm in the current study, which is within the range that does not require haemostatic component transfusions; Blasi et al.6 indicated that patients undergoing liver transplantation with an A10 in EXTEM at least 35 mm (which predicts a maximum clot firmness of 45 mm) were not associated with signs of bleeding. Viscoelastic coagulation monitoring devices such as ROTEM have been demonstrated as the best perioperative tool to guide coagulation management and help reduce transfusion.7 Acknowledgements relating to this article Assistance with the letter: none. Financial support and sponsorship: none. Conflicts of interest: FHS received honoraria from the speakers’ bureau of CSL Behring and research support from TEM International.