Patients with cirrhosis have a disbalance between coagulation and fibrinolysis resulting in a prothrombotic phenotype
Ruth Anne Laura Willems 1),2),3),4); Alberto Zanetto 5),6); Elena Campello 7),8); Ilaria de Simone 1); Cristiana Bulato 8); Joke Konings 1); Matthijs Kramer 9); Samia Tufaha 1); Francesco Paolo Russo 5),6); Marco Senzolo 6); Patrizia Burra 5),6); Hugo ten Cate 2),3),4),10); Judith de Vos-Geelen 2),11); Mark Roest 12); Paolo Simioni 7),13); Bas de Laat 1),4),12); Dana Huskens 1),12).
1) Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
2) Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
3) Thrombosis Expert Center Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
4) Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, Maastricht, The Netherlands
5) Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
6) Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy
7) Department of Medicine (DIMED), University of Padova, Padova, Italy
8) Internal Medicine and Thrombotic and Haemorrhagic Disease Unit, Padova University Hospital, Padova, Italy
9) Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
10) Center of Thrombosis and Haemostasis, Gutenberg University Medical Center, Mainz, Germany
11) GROW, Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands
12) Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands
13) First Chair of Internal Medicine and Thrombotic and Haemorrhagic Disease Unit, Padova University Hospital, Padova, Italy
Abstract
Background
Patients with cirrhosis develop multiple hemostatic alterations. Although fibrinolysis is also affected by liver disease, studies have produced conflicting results, highlighting the need for a reliable fibrinolysis assay. Assessing the kinetics of plasmin generation (PG) is a new method to study the fibrinolytic state of cirrhosis patients.
Objectives
This study aimed to compare fibrinolysis between patients with cirrhosis and healthy subjects.
Methods
This single-center cohort study included cirrhosis patients from the Padova University Hospital. Fibrinolysis and hemostasis were assessed with PG, thrombin generation (TG), and clot lysis time. To quantify malalignment between TG and PG, ratios were calculated.
Results
In total, 101 patients with cirrhosis (Child–Pugh A/B/C: 36/24/41) and 20 healthy subjects were included. Compared with healthy subjects, patients showed a significantly lower endogenous plasmin potential and plasmin peak. The PG capacity decreased with liver disease severity. The lag time to PG was prolonged in patients. No differences in endogenous thrombin potential and lag time were found when comparing TG profiles. Patients had a shorter clot lysis time. Increased TG/PG ratios for the endogenous plasmin potential and plasmin peak were found in patients compared with that in controls. TG/PG ratios increased with liver disease severity.
Conclusion
Patients with cirrhosis have a complex fibrinolytic profile, with a delayed and decreased capacity to generate plasmin and a more rapid clot lysis. A disbalance was found between coagulation and fibrinolysis, with a normal-to-increased TG capacity and a decreased PG capacity. These results support the theory that cirrhosis patients are in a prothrombotic state.