Evidence for a rebalanced hemostatic system in pediatric liver transplantation: A prospective cohort study.

In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis.

Werner MJM ，de Meijer VE ，Adelmeijer J ，de Kleine RHJ ，Scheenstra R ，Bontemps STH ，Reyntjens KMEM ，Hulscher JBF ，Lisman T ，Porte RJ ... -  《-》

Global hemostatic status in patients with acute-on-chronic liver failure and septics without underlying liver disease.

Essentials Liver diseases are associated with profound hemostatic changes proportional to severity of illness. Hemostatic changes in acute-on-chronic liver failure (ACLF) may in part reflect critical illness. Hemostatic changes in ACLF partly overlap with those in sepsis, with rebalanced hemostasis in both. Patients with sepsis had hyperfibrinogenemia, associated with a thrombogenic clot structure. ABSTRACT: Background Even the sickest patients with chronic liver disease (CLD), such as those with acute-on-chronic liver failure (ACLF) remain in hemostatic balance due to a concomitant decline in pro- and antihemostatic factors. Objectives We aimed to study whether the hemostatic status in ACLF is merely an exaggeration from the status in patients with compensated and acutely decompensated cirrhosis, or whether sepsis-associated hemostatic changes contribute. Methods We performed extensive hemostatic profiling in 31 adult patients with ACLF, 20 patients with sepsis without underlying CLD, and 40 healthy controls. Results We found similarly elevated plasma levels of the platelet adhesive protein von Willebrand factor (VWF) and decreased levels of the VWF-regulating protease ADAMTS13 in both groups compared to healthy controls. In vivo markers of activation of coagulation (thrombin-antithrombin III, D-dimer) were similarly elevated in both groups compared to controls, but ex vivo thrombin-generating capacity was similar between patients and controls, despite a much more profound international normalized ratio elevation in ACLF. Plasma fibrinogen levels were much higher in septics, which was accompanied by a decreased ex vivo clot permeability and an increase in ex vivo resistance to clot lysis. All hemostatic parameters were remarkably stable over the first 10 days after admission. Conclusions We have found hemostatic changes in ACLF to partially overlap with that of patients with sepsis, and evidence of preserved hemostatic capacity in both patient groups. The notable difference was a profound hyperfibrinogenemia, associated with a thrombogenic clot structure and a marked ex vivo resistance to fibrinolysis in patients with sepsis.

Lisman T ，Arefaine B ，Adelmeijer J ，Zamalloa A ，Corcoran E ，Smith JG ，Bernal W ，Patel VC ... -  《-》

The concept of rebalanced hemostasis in patients with liver disease: Communication from the ISTH SSC working group on hemostatic management of patients with liver disease.

Patients with liver diseases acquire complex alterations in their hemostatic system that may lead to abnormalities in routine diagnostic test of hemostasis. Thrombocytopenia, prolongations in the prothrombin time and activated partial thromboplastin time, and decreased plasma fibrinogen are common in patients with advanced liver disease. Historically, liver diseases therefore have been classified as an acquired bleeding disorder. Laboratory and clinical observations have demonstrated that although routine diagnostic tests of hemostasis suggest a hypocoagulable state, patients with liver disease also tend to develop thrombotic events. Overall, patients have commensurate changes in both pro- and antihemostatic pathways. This new hemostatic balance, however, appears much more fragile than the hemostatic balance in individuals with normal liver function, and patients with liver disease can readily experience both hemostasis-related bleeding and thrombotic events. These insights into the hemostatic balance in patients with liver disease have led to revised recommendations for clinical management of hemostasis. In 2020, an SSC working group within the ISTH has been founded with the aim to disseminate new concepts on prevention and treatment of bleeding and thrombosis in patients with liver disease. The current document will outline the hemostatic changes in patients with liver disease, the limitations of routine diagnostic tests of hemostasis, and the concept of rebalanced hemostasis.

Lisman T ，Hernandez-Gea V ，Magnusson M ，Roberts L ，Stanworth S ，Thachil J ，Tripodi A ... -  《-》

How to assess hemostasis in patients with severe liver disease.

Lisman T 《-》

Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment.

Hartmann M ，Szalai C ，Saner FH 《-》