Altered clot formation and lysis are associated with increased fibrinolytic activity in ascites in patients with advanced cirrhosis.
Ascites
Clot formation/lysis
Coagulopathy
Fibrinolysis
Liver cirrhosis
Journal
Internal and emergency medicine
ISSN: 1970-9366
Titre abrégé: Intern Emerg Med
Pays: Italy
ID NLM: 101263418
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
02
03
2020
accepted:
12
05
2020
pubmed:
24
5
2020
medline:
14
9
2021
entrez:
24
5
2020
Statut:
ppublish
Résumé
Analysis of coagulation disorders and assessment of rebalanced hemostasis with the use of traditional coagulation assays is challenging in cirrhotic patients. Therefore, alternative tests are under investigation for the evaluation of coagulopathy in this specific setting. Aim of this study was to analyze the modifications of clot structure and function in cirrhotic patients with different degrees of severity. Cirrhotic patients referred to our Unit were consecutively enrolled. Global test measurements, including clot and lysis assays, clot lysis time, and determination of other fibrinolytic parameters, were performed. Analyses of clot formation, morphology, and lysis were performed with a turbidimetric clotting and lysis assay (EuroCLOT). Lysis of a tissue factor-induced clot by exogenous tissue plasminogen activator was analyzed by studying the modifications of turbidity during clot formation and the following lysis. We evaluated coagulative and fibrinolytic parameters in both plasma and ascites. Urokinase plasminogen activator (uPA) and gelatinase activity in ascites were also measured. We analyzed data from 33 cirrhotic patients (11 in Child-Pugh class A; 22 in class B or C and with ascites) and 21 healthy subjects (HS). In class B/C patients prolonged latency time, a decline in clotting absorbance, and decreased fibrin formation were observed in comparison with class A and HS. Generated curves and Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) progressively declined from HS to class C patients, whereas levels of plasminogen activator inhibitor-1 and tissue plasminogen activator increased. D-dimer levels were markedly increased in ascites, together with significantly smaller levels of TAFI, αlfa2-antiplasmin, and plasminogen. Caseinolytic activity was also present. Class C patients showed smaller amount of uPA and significantly lower levels of matrix metallopeptidases (MMP)2 in ascites in comparison with Class B subjects. Clot formation and lysis are altered in cirrhosis and fibrinolysis is activated in ascites. Ascitic levels of uPA and MMP2 are reduced and inversely related to the severity of liver disease.
Identifiants
pubmed: 32445164
doi: 10.1007/s11739-020-02375-3
pii: 10.1007/s11739-020-02375-3
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
339-347Subventions
Organisme : Università degli Studi di Firenze
ID : ex 60% (fondi dipartimentali)
Organisme : Università degli Studi di Firenze
ID : ex 60% (fondi dipartimentali - Prof. Romanelli)
Organisme : MIUR
ID : 20100_M4738 "Hepatic Steatosis" (Grant MIUR 40% Prof. Romanelli)
Références
Tripodi A, Mannucci PM (2011) The coagulopathy of chronic liver disease. N Engl J Med 365:147–156
doi: 10.1056/NEJMra1011170
Lisman T, Porte RJ (2010) Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Bloodì 116:878–885
doi: 10.1182/blood-2010-02-261891
Allison MG, Shanholtz CB, Sachdeva A (2016) Hematological issues in liver disease. Crit Care Clin 32:385–396
doi: 10.1016/j.ccc.2016.03.004
Tripodi A, Primignani M, Mannucci PM, Caldwell SH (2017) Changing concepts of cirrhotic coagulopathy. Am J Gastroenterol 112:274–281
doi: 10.1038/ajg.2016.498
Carter AM, Cymbalista CM, Spector TD, Grant PJ, Investigators EuroCLOT (2007) Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol 27:2783–2789
doi: 10.1161/ATVBAHA.107.153221
Gines P, Arroyo V, Rodes J, Schrier RW (eds) (2005) Ascites and renal dysfunction in liver disease. Malden, Blackwell, pp 174–185
doi: 10.1002/9780470987476.ch14
Lafleur MA, Hollenberg MD, Atkinson SJ, Knäuper V, Murphy G, Edwards DR (2001) Activation of pro-(matrix metalloproteinase-2) (pro-MMP-2) by thrombin is membrane-type-MMP-dependent in human umbilical vein endothelial cells and generates a distinct 63 kDa active species. Biochem J 357:107–115
doi: 10.1042/bj3570107
European Association for the Study of the Liver (2018) Clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol 69:406–460
doi: 10.1016/j.jhep.2018.03.024
Lami D, Cellai AP, Antonucci E et al (2014) Residual perfusion defects in patients with pulmonary embolism are related to impaired fibrinolytic capacity. Thromb Res 134:737–741
doi: 10.1016/j.thromres.2014.07.013
Lisman T, DeGroot PG, Meijers JC, Rosendaal FR (2005) Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 105:1102–1105
doi: 10.1182/blood-2004-08-3253
Cellai AP, Lami D, Magi A et al (2010) Assessment of fibrinolytic activity by measuring the lysis time of a tissue-factor-induced clot: a feasibility evaluation. Clin Appl Thromb Hemost 16:337–344
doi: 10.1177/1076029608325542
Lisman T, Leebeek FW, Mosnier LO et al (2001) Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 121:131–139
doi: 10.1053/gast.2001.25481
Fibbi G, Pucci M, Grappone C et al (1999) Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. Hepatology 29:868–878
doi: 10.1002/hep.510290343
Pepper MS, Vassalli JD, Montesano R, Orci L (1987) Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 105:2535–2541
doi: 10.1083/jcb.105.6.2535
Serratì S, Chillà A, Laurenzana A et al (2013) Systemic sclerosis endothelial cells recruit and activate dermal fibroblasts by induction of a connective tissue growth factor (CCN2)/transforming growth factor β-dependent mesenchymal-to-mesenchymal transition. Arthritis Rheum 65:258–269
doi: 10.1002/art.37705
Martinez J, MacDonald KA, Palascak JE (1983) The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains. Blood 61:1196–1202
doi: 10.1182/blood.V61.6.1196.1196
Palascak JE, Martinez J (1977) Dysfibrinogenemia associated with liver disease. J Clin Invest 60:89–95
doi: 10.1172/JCI108773
Lloyd-Donald P, Vasudevan A, Angus P et al (2017) Coagulation in acutely ill patients with severe chronic liver disease: insights from thromboelastography. J Crit Care 38:215–224
doi: 10.1016/j.jcrc.2016.10.030
Blasi A, Calvo A, Prado V et al (2018) Coagulation failure in patients with Acute-on-Chronic Liver Failure (ACLF) and decompensated cirrhosis: beyond INR. Hepatology 68:1621–1632
doi: 10.1002/hep.30103
Premukar M, Saxena P, Rangegowda D et al (2019) Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute-on-chronic liver failure: an observational cohort study. Liver Int 39:694–704
doi: 10.1111/liv.14034
Coleman M, Finlayson N, Bettigole RE et al (1975) Fibrinogen survival in cirrhosis: improvement by "low dose" heparin. Ann Intern Med 83:79–81
doi: 10.7326/0003-4819-83-1-79
Dettori AG, Ponari O, Civardi E et al (1977) Impaired fibrin formation in advanced cirrhosis. Haemostasis 6:137–148
pubmed: 863294
Francis JL, Armstrong DJ (1982) Acquired dysfibrinogenaemia in liver disease. J Clin Pathol 35:667–672
doi: 10.1136/jcp.35.6.667
Hugenholtz GC, Macrae F, Adelmeijer J et al (2016) Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen. J Thromb Haemost 14:1054–1066
doi: 10.1111/jth.13278
Zanetto A, Senzolo M, Vitale A et al (2017) Thromboelastometry hypercoagulable profiles and portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma. Dig Liver Dis 49:440–445
doi: 10.1016/j.dld.2016.12.019
Becatti M, Mannucci A, Argento F et al (2018) Fibrinogen structural changes in cirrhosis-associated coagulopathy: the role of oxidative stress. Blood Transfus 16(Suppl 4):s459
Lisman T, Ariëns RA (2016) Alterations in fibrin structure in patients with liver diseases. Semin Thromb Hemost 42:389–396
doi: 10.1055/s-0036-1572327
Colucci M, Binetti BM, Branca MG et al (2003) Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 38:230–237
doi: 10.1053/jhep.2003.50277
Gresele P, Binetti BM, Branca G et al (2008) TAFI deficiency in liver cirrhosis: relation with plasma fibrinolysis and survival. Thromb Res 121:763–768
doi: 10.1016/j.thromres.2007.08.011
van De Water L, Carr JM, Aronson D, McDonagh J (1986) Analysis of elevated fibrin(ogen) degradation product levels in patients with liver disease. Blood 67:1468–1147
doi: 10.1182/blood.V67.5.1468.1468
Bakker CM, Knot EA, Stibbe J, Wilson JH (1992) Disseminated intravascular coagulation in liver cirrhosis. J Hepatol 15:330–335
doi: 10.1016/0168-8278(92)90064-V
Tripodi A, Anstee QM, Sogaard KK et al (2011) Hypercoagulability in cirrhosis causes and consequences. J Thromb Haemost 9:1713–1723
doi: 10.1111/j.1538-7836.2011.04429.x
Agarwal S, Joyner KA Jr, Swaim MW (2000) Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease. Am J Gastroenterol 95:3218–3224
doi: 10.1111/j.1572-0241.2000.03299.x
Toschi V, Rocchini GM, Motta A et al (1993) The hyperfibrinolytic state of liver cirrhosis: possible pathogenetic role of ascites. Biomed Pharmacother 47:345–352
doi: 10.1016/0753-3322(93)90084-X
LeVeen HH, Ip M, Ahmed N et al (1987) Coagulopathy post peritoneovenous shunt. Ann Surg 205:305–311
doi: 10.1097/00000658-198703000-00015
Marshall BC, Santana A, Xu QP et al (1993) Metalloproteinases and tissue inhibitor of metalloproteinases in mesothelial cells. Cellular differentiation influences expression. J Clin Invest 91:1792–1799
doi: 10.1172/JCI116390
Buhac I, Jarmolych J (1978) Histology of the intestinal peritoneum in patients with cirrhosis of the liver and ascites. Am J Dig 23:417–422
doi: 10.1007/BF01072924