Fibrin clot quality in acutely ill cirrhosis patients: Relation with outcome and improvement with coagulation factor concentrates.
blood coagulation
cirrhosis
factor XIII
fibrin
haemorrhage
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
13
11
2021
received:
08
09
2021
accepted:
02
12
2021
pubmed:
12
12
2021
medline:
4
3
2022
entrez:
11
12
2021
Statut:
ppublish
Résumé
Patients with liver disease may acquire substantial changes in their hemostatic system, which are most pronounced in patients who are critically ill. Changes in the quality of the fibrin clot in critically ill patients have not been studied in detail. Here we assessed markers of fibrin clot quality and effects of coagulation factor concentrates in patients with acutely decompensated (AD) cirrhosis and acute on chronic liver failure (ACLF). We measured plasma levels of fibrinogen, factor XIII, prothrombin and performed thrombin generation assays in 52 AD patients, 58 ACLF patients and 40 controls. In addition, we examined the effects of coagulation factor concentrates on functional assays of fibrin quality. We found increased thrombin generating capacity in both AD and ACLF in comparison with healthy controls. Plasma levels of prothrombin, fibrinogen, and factor XIII were lower in patients compared to controls, appeared lower in ACLF compared to AD patients, and were related to clinical outcomes. Fibrinogen concentrate, but not factor XIII or prothrombin complex concentrate, improved clot quality in vitro. Prothrombin complex concentrate increased the resistance of the clot to break down. We have demonstrated elevated thrombin generation but decreased plasma levels of prothrombin, fibrinogen and FXIII in acutely ill patients with cirrhosis. In addition, we showed that fibrinogen concentrate and PCCs, but not factor XIII concentrate, improve clot properties in patient plasma. Whether there is true clinical benefit from coagulation factor concentrates in prevention or treatment of bleeding requires further study. Patients with liver diseases are at risk of bleeding, but mechanisms involved in this bleeding risk are incompletely understood. We studied components that determine the stability of the blood clot and found that concentrations of certain proteins involved in clot stability are present in low levels in acutely ill patients with liver disease. We furthermore demonstrated that some clinically available drugs improve the stability of blood clots from these patients in a test tube.
Sections du résumé
BACKGROUND & AIMS
Patients with liver disease may acquire substantial changes in their hemostatic system, which are most pronounced in patients who are critically ill. Changes in the quality of the fibrin clot in critically ill patients have not been studied in detail. Here we assessed markers of fibrin clot quality and effects of coagulation factor concentrates in patients with acutely decompensated (AD) cirrhosis and acute on chronic liver failure (ACLF).
METHODS
We measured plasma levels of fibrinogen, factor XIII, prothrombin and performed thrombin generation assays in 52 AD patients, 58 ACLF patients and 40 controls. In addition, we examined the effects of coagulation factor concentrates on functional assays of fibrin quality.
RESULTS
We found increased thrombin generating capacity in both AD and ACLF in comparison with healthy controls. Plasma levels of prothrombin, fibrinogen, and factor XIII were lower in patients compared to controls, appeared lower in ACLF compared to AD patients, and were related to clinical outcomes. Fibrinogen concentrate, but not factor XIII or prothrombin complex concentrate, improved clot quality in vitro. Prothrombin complex concentrate increased the resistance of the clot to break down.
CONCLUSIONS
We have demonstrated elevated thrombin generation but decreased plasma levels of prothrombin, fibrinogen and FXIII in acutely ill patients with cirrhosis. In addition, we showed that fibrinogen concentrate and PCCs, but not factor XIII concentrate, improve clot properties in patient plasma. Whether there is true clinical benefit from coagulation factor concentrates in prevention or treatment of bleeding requires further study.
LAY SUMMARY
Patients with liver diseases are at risk of bleeding, but mechanisms involved in this bleeding risk are incompletely understood. We studied components that determine the stability of the blood clot and found that concentrations of certain proteins involved in clot stability are present in low levels in acutely ill patients with liver disease. We furthermore demonstrated that some clinically available drugs improve the stability of blood clots from these patients in a test tube.
Identifiants
pubmed: 34894081
doi: 10.1111/liv.15132
pmc: PMC9299765
doi:
Substances chimiques
Blood Coagulation Factors
0
Fibrin
9001-31-4
Fibrinogen
9001-32-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
435-443Informations de copyright
© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.
Références
Thromb Haemost. 2021 Oct;121(10):1317-1325
pubmed: 33450778
Hematol Transfus Cell Ther. 2021 Jul-Sep;43(3):280-286
pubmed: 32737021
JAMA. 2016 Feb 23;315(8):801-10
pubmed: 26903338
BMC Anesthesiol. 2019 Jun 11;19(1):97
pubmed: 31185916
Hepatol Commun. 2019 Feb 05;3(4):513-524
pubmed: 30976742
Liver Int. 2022 Feb;42(2):435-443
pubmed: 34894081
J Thromb Haemost. 2012 Oct;10(10):2179-81
pubmed: 23193585
J Hepatol. 2020 Jan;72(1):85-94
pubmed: 31536747
N Engl J Med. 2011 Jul 14;365(2):147-56
pubmed: 21751907
Gastroenterology. 2019 Jul;157(1):34-43.e1
pubmed: 30986390
J Thromb Haemost. 2013 Feb;11(2):307-14
pubmed: 23176206
Eur J Trauma Emerg Surg. 2021 Aug;47(4):1057-1063
pubmed: 31894349
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):e88-99
pubmed: 21836064
Gastroenterology. 2013 Jun;144(7):1426-37, 1437.e1-9
pubmed: 23474284
Blood. 2010 Aug 12;116(6):878-85
pubmed: 20400681
Clin Appl Thromb Hemost. 2017 Nov;23(8):1028-1035
pubmed: 27628534
Diabetologia. 2005 Jun;48(6):1198-206
pubmed: 15864538
Blood. 2002 Jan 1;99(1):175-9
pubmed: 11756168
Liver Int. 2018 Nov;38(11):1988-1996
pubmed: 29768734
Hepatology. 2020 Apr;71(4):1381-1390
pubmed: 31465557
Arterioscler Thromb Vasc Biol. 1999 Aug;19(8):2012-6
pubmed: 10446086
J Crit Care. 2018 Feb;43:54-60
pubmed: 28843665
Liver Int. 2017 Apr;37(4):562-568
pubmed: 27634287
Dig Liver Dis. 2019 Oct;51(10):1409-1415
pubmed: 30967339
Blood Coagul Fibrinolysis. 2020 Jun;31(4):253-257
pubmed: 32332276
Liver Transpl. 2019 Mar;25(3):359-361
pubmed: 30657246
Lancet. 2020 Jun 20;395(10241):1927-1936
pubmed: 32563378
Hepatology. 2020 Oct;72(4):1327-1340
pubmed: 32614088
PLoS Med. 2008 May 6;5(5):e97
pubmed: 18462012
J Clin Invest. 2014 Aug;124(8):3590-600
pubmed: 24983320
Hepatology. 2021 Jan;73(1):366-413
pubmed: 33219529
Semin Thromb Hemost. 2020 Sep;46(6):716-723
pubmed: 32820482
J Thromb Haemost. 2021 Mar;19(3):664-676
pubmed: 33219597
J Thromb Haemost. 2020 Oct;18(10):2440-2443
pubmed: 32856769
Semin Thromb Hemost. 2020 Sep;46(6):656-664
pubmed: 32757184
Hepatology. 2016 Aug;64(2):556-68
pubmed: 27124745
Blood Adv. 2018 Jan 03;2(1):25-35
pubmed: 29344582
Intern Emerg Med. 2012 Apr;7(2):139-44
pubmed: 21298360