LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Hugenholtz, GCG; Macrae, F; Adelmeijer, J; Dulfer, S; Porte, RJ; Lisman, T; Ariëns, RAS (2016)
Publisher: Wiley
Languages: English
Types: Article
Subjects:

Classified by OpenAIRE into

mesheuropmc: circulatory and respiratory physiology
Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however, clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. Background and Objectives: Patients with cirrhosis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods: We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrinogen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results: Tissue factor and thrombin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in turbidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot permeability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions: Delayed clot formation in cirrhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrinogen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Ldisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: Evidence and clinical consequences. Blood. 2010;116:878-85. e
    • 2. Ttripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011; 365:147- 56. p
    • 3. Northup PG, Sundaram V, Fallon MB, Reddy KR, Balogun RA, Sanyal AJ, Anstee QM, Hoffman MR, Ikura eY,Caldwell SH, Coagulation in Liver Disease Group. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost. 2008;6:2-9. c
    • 4. Anstee QM, Wright M, Goldin R, Thursz MR. Parenchymal extinction: Coagulation and hepatic c
    • fibrogenesis. Clin Liver Dis. 2009;13:117-26.
    • 5. Anstee QM, Goldin RD, Wright M, Martinelli A, Cox R, Thursz MR. Coagulation status modulates murine hepatic fibrogenesis: Implications for the development of novel therapies. J Thromb Haemost. 2008;6:1336-43. e
    • 6. Vlilla E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, Tata C, Zecchini R, Gitto S, Petta S, Lei B, Bernabucci V, Vukotic R, De Maria N, Schepis F, Karampatou A, Caporali C, Simoni L, Del Buono M, c
    • advanced cirrhosis. Gastroenterology. 2012;143:1253,1260.e4. t
    • 8. Tripodi A, Primignani M, Lemma L, Chantarangkul V, Dell'Era A, Iannuzzi F, Aghemo A, Mannucci PM. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple labodratory method. Hepatology. 2010;52:249-55.
    • 9. Leisman T, Bongers TN, Adelmeijer J, Janssen HL, de Maat MP, de Groot PG, Leebeek FW. Elevated levetlsof von willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology. 2006;44:53-61. p
    • 10. Hugenholtz GC, Adelmeijer J, Meijers JC, Porte RJ, Stravitz RT, Lisman T. An unbalance between von ewillebrand factor and ADAMTS13 in acute liver failure: Implications for hemostasis and clinical outcome. Hepatology. 2013;58:752-61. c
    • 11. Undas A, Ariens RA. Fibrin clot structure and function: A role in the pathophysiology of arterial c
    • and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2011;31:e88-99.
    • 12. Undas A, Szuldrzynski K, Stepien E, Zalewski J, Godlewski J, Tracz W, Pasowicz M, Zmudka K. Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: Effects of inflammation and oxidative stress. Atherosclerosis. 2008;196:551-7. e
    • 13. lUndas A, Zawilska K, Ciesla-Dul M, Lehmann-Kopydlowska A, Skubiszak A, Ciepluch K, Tracz W. Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in c
    • their relatives. Blood. 2009;114:4272-8. i
    • 14. tCollet JP, Allali Y, Lesty C, Tanguy ML, Silvain J, Ankri A, Blanchet B, Dumaine R, Gianetti J, Payot L, Wreisel JW, Montalescot G. Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis. Arterioscler Thromb Vasc Biol. 2006;26:2567-73.
    • 15. AUndasA, Plicner D, Stepien E, Drwila R, Sadowski J. Altered fibrin clot structure in patients with advanced coronary artery disease: A role of C-reactive protein, lipoprotein(a) and homocysteine. J Thromb Haemost. 2007;5:1988-90. d
    • 16. Martinez J, Palascak JE, Kwasniak D. Abnormal sialic acid content of the dysfibrinogenemia assoeciated with liver disease. J Clin Invest. 1978;61:535-8. t
    • 17. Martinez J, MacDonald KA, Palascak JE. The role of sialic acid in the dysfibrinogenemia associated with liver disease: Distribution of sialic acid on the constituent chains. Blood. 1983;61:1196-202. p
    • 18. Lisman T, Leebeek FW, Mosnier LO, Bouma BN, Meijers JC, Janssen HL, Nieuwenhuis HK, De e
    • Groot PG. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with incrceased plasma fibrinolysis. Gastroenterology. 2001;121:131-9.
    • 19. cPotze W, Adelmeijer J, Porte RJ, Lisman T. Preserved clot formation detected by the thrombodynamics analyzer in patients with cirrhosis. Thromb Res. 2015;135:1012-6 29. cSmith EL, Cardinali B, Ping L, Ariens RA, Philippou H. Elimination of coagulation factor XIII from fibrinogen preparations. J Thromb Haemost. 2013;11:993-5.
    • 47. eKremers RM, Wagenvoord RJ, Hemker HC. The effect of fibrin(ogen) on thrombin generation and declay. Thromb Haemost. 2014;112:486-94.
    • 48. cPaton LN, Mocatta TJ, Richards AM, Winterbourn CC. Increased thrombin-induced polyimerization of fibrinogen associated with high protein carbonyl levels in plasma from patients post tmyocardial infarction. Free Radic Biol Med. 2010;48:223-9.
    • 54. Northup PG, Sundaram V, Fallon MB, Reddy KR, Balogun RA, Sanyal AJ, Anstee QM, Hoffman MR, Ikura Y, Caldwell SH, Coagulation in Liver Disease Group. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost. 2008;6:2-9. e
    • 55. lBecatti M, Marcucci R, Bruschi G, Taddei N, Bani D, Gori AM, Giusti B, Gensini GF, Abbate R, Fiorillo C. Oxidative modification of fibrinogen is associated with altered function and structure in c
    • the subacute phase of myocardial infarction. Arterioscler Thromb Vasc Biol. 2014;34:1355-61. i
    • 56. tParastatidis I, Thomson L, Burke A, Chernysh I, Nagaswami C, Visser J, Stamer S, Liebler DC, Kolirakos G, Heijnen HF, Fitzgerald GA, Weisel JW, Ischiropoulos H. Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor. J Biol Chem. 2008;283:33846-53.
    • 57. ABaruaRS, Sy F, Srikanth S, Huang G, Javed U, Buhari C, Margosan D, Ambrose JA. Effects of cigarette smoke exposure on clot dynamics and fibrin structure: An ex vivo investigation. Arterioscler Thromb Vasc Biol. 2010;30:75-9. d
    • 58. Martinez M, Cuker A, Mills A, Lightfoot R, Fan Y, Tang WH, Hazen SL, Ischiropoulos H. Nitrated fibreinogen is a biomarker of oxidative stress in venous thromboembolism. Free Radic Biol Med. 201t2;53:230-6.
    • 59. Miniati M, Fiorillo C, Becatti M, Monti S, Bottai M, Marini C, Grifoni E, Formichi B, Bauleo C, p
    • Arcangeli C, Poli D, Nassi PA, Abbate R, Prisco D. Fibrin resistance to lysis in patients with pulmonary hypeertension other than thromboembolic. Am J Respir Crit Care Med. 2010;181:992-6.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article