Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Abstract

Background and Aims Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin‐generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma. Methods Thrombin‐generating capacity in WB and plasma were assessed with a near‐patient WB‐TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed. Results Thirty‐four patients with cirrhosis and twenty‐two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB‐TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB‐TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma. Conclusions The WB‐TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma‐TG. The clinical value of this assay needs further validation.

Evaluation of Coagulation, Fibrinolysis and Endothelial Biomarkers in Cirrhotic Patients With or Without Portal Venous Thrombosis

“… 14 Although a hemostatic balance is reached in cirrhosis, this equilibrium is more fragile and can easily lead to a hypo- or hyper-coagulable state. 15 In recent years, it has been evident that appropriately assessing patients for the risk of bleeding and thrombosis cannot be done with standard coagulation tests, such as PT, INR or APTT. 5 As our study showed, many cirrhotic patients develop PVT despite elevated PT, INR and APTT.…”

Added Value of Blood Cells in Thrombin Generation Testing

“…Moreover, we recently showed that erythrocytes augmented peak thrombin level even in the presence of high platelet count (87). Furthermore, both in a group of healthy adults (87) and cirrhotic patients (112) we observed a positive correlation between hematocrit and the peak of WB-TG, indicating that erythrocytes have a positive effect on the velocity of WB-TG.…”

Efficacy of pro‐ and anticoagulant strategies in plasma of patients undergoing hepatobiliary surgery

“…26,39 In vitro and ex vivo studies have demonstrated little to no prohemostatic effect of FFP by thrombin generation tests in patients with cirrhosis. 25,40 Although prophylactic administration of FFP in 43,44 In addition, it is unknown which level of ETP represents the optimal pro-or anticoagulant status; therefore, we do not have ETP target levels for management of thrombosis or bleeding. To incorporate dose adjustments in further studies, we would need such information to be able to adjust the dosing of pro-or anticoagulants in this specific population.…”

“…Thrombin generation is thus far only used in a research setting. It is a relatively cumbersome test and not yet ready for clinical use, although the automated test (Genesia) has been launched and whole blood thrombin generation tests that may be suitable as a point‐of‐care test are in development 43,44 . In addition, it is unknown which level of ETP represents the optimal pro‐ or anticoagulant status; therefore, we do not have ETP target levels for management of thrombosis or bleeding.…”