Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Internal and Emergency Medicine
Published in: Internal and Emergency Medicine 1/2010

01-02-2010 | IM - Review

Abnormalities of hemostasis and bleeding in chronic liver disease: the paradigm is challenged

Authors: Armando Tripodi, Massimo Primignani, Pier Mannuccio Mannucci

Published in: Internal and Emergency Medicine | Issue 1/2010

Login to get access

Abstract

Chronic liver disease is characterized by a global hemostatic defect including platelet–vessel wall interaction (primary hemostasis), coagulation and fibrinolysis that may cause abnormalities of the relevant laboratory tests. The causal relationship between abnormal tests and bleeding has been widely accepted, despite the fact that abnormal tests are poorly associated with the timing and incidence of actual bleeding. In this article, we review recent evidence from the literature that disputes the above paradigm, and opens new venues for laboratory/clinical research and patient management in this field.
Literature
1.
Hedner U, Erhardtsen E (2003) Hemostatic disorders in liver disease. In: Schiff ER et al (eds) Schiff’s disease of the liver. Lippincott Williams and Wilkins, Philadelphia, pp 625–636
2.
3.
Ordinas A, Escolar G, Cirera I, Vinas M, Cobo F, Bosch J et al (1996) Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions. Hepatology 24:1137–1142CrossRefPubMed
4.
Thomas DP, Ream VJ, Stuart RK (1967) Platelet aggregation in patients with Laennec’s cirrhosis of the liver. N Engl J Med 276:1344–1348PubMed
5.
Ballard HS, Marcus AJ (1976) Platelet aggregation in portal cirrhosis. Arch Intern Med 136:316–319CrossRefPubMed
6.
Laffi G, La Villa G, Pinzani M, Ciabattoni G, Patrignani P, Mannelli M et al (1986) Altered renal and platelet arachidonic acid metabolism in cirrhosis. Gastroenterology 90:274–282PubMed
7.
Laffi G, Cominelli F, Ruggiero M, Fedi S, Chiarugi VP, La Villa G et al (1988) Altered platelet function in cirrhosis of the liver: impairment of inositol lipid and arachidonic acid metabolism in response to agonists. Hepatology 8:1620–1626CrossRefPubMed
8.
Laffi G, Daskalopoulos G, Kronborg I, Hsueh W, Gentilini P, Zipser RD (1986) Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac. Gastroenterology 90:182–187PubMed
9.
Laffi G, Marra F, Failli P, Ruggiero M, Cecchi E, Carloni V et al (1993) Defective signal transduction in platelets from cirrhotics is associated with increased cyclic nucleotides. Gastroenterology 105:148–156PubMed
10.
Laffi G, Marra F, Gresele P, Romagnoli P, Palermo A, Bartolini O et al (1992) Evidence for a storage pool defect in platelets from cirrhotic patients with defective aggregation. Gastroenterology 103:641–646PubMed
11.
Ordinas A, Maragall S, Castillo R, Nurden AT (1978) A glycoprotein I defect in the platelets of three patients with severe cirrhosis of the liver. Thromb Res 13:297–302CrossRefPubMed
12.
Grant A, Neuberger J (1999) Guidelines on the use of liver biopsy in clinical practice. British Society of Gastroenterology. Gut 45(Suppl 4):IV1–IV11CrossRefPubMed
13.
Violi F, Leo R, Vezza E, Basili S, Cordova C, Balsano F (1994) Bleeding time in patients with cirrhosis: relation with degree of liver failure and clotting abnormalities. C.A.L.C. Group. Coagulation Abnormalities in Cirrhosis Study Group. J Hepatol 20:531–536CrossRefPubMed
14.
Boberg KM, Brosstad F, Egeland T, Egge T, Schrumpf E (1999) Is a prolonged bleeding time associated with an increased risk of hemorrhage after liver biopsy? Thromb Haemost 81:378–381PubMed
15.
Mannucci PM, Vicente V, Vianello L, Cattaneo M, Alberca I, Coccato MP et al (1986) Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood 67:1148–1153PubMed
16.
Burroughs AK, Matthews K, Qadiri M, Thomas N, Kernoff P, Tuddenham E et al (1985) Desmopressin and bleeding time in patients with cirrhosis. Br Med J 291:1377–1381CrossRef
17.
Cattaneo M, Tenconi PM, Alberca I, Garcia VV, Mannucci PM (1990) Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis. Thromb Haemost 64:358–360PubMed
18.
de Franchis R, Arcidiacono PG, Carpinelli L, Andreoni B, Cestari L, Brunati S et al (1993) Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: a multicenter, double-blind study. New Italian Endoscopic Club. Hepatology 18:1102–1107CrossRefPubMed
19.
Wong AY, Irwin MG, Hui TW, Fung SK, Fan ST, Ma ES (2003) Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can J Anaesth 50:14–20CrossRefPubMed
20.
Lisman T, Bongers TN, Adelmeijer J, Janssen HL, de Maat MP, de Groot PG, Leebeek WF (2006) Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 44:53–61CrossRefPubMed
21.
Escolar G, Cases A, Viñas M, Pino M, Calls J, Cirera I, Ordinas A (1999) Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100): influence of hematocrit elevation. Haematologica 84:614–619PubMed
22.
Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, Tripodi A, Sanyal AJ (2006) Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 44:1039–1046CrossRefPubMed
23.
Esmon CT (1989) The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 264:4743–4746PubMed
24.
Tripodi A, Caldwell SH, Hoffman M, Trotter JF, Sanyal AJ (2007) The prothrombin time test as a measure of bleeding risk and prognosis in liver disease. Aliment Pharmacol Ther 26:141–148CrossRefPubMed
25.
Tripodi A, Ramenghi LA, Chantarangkul V, De Carli A, Clerici M, Groppo M, Mosca F, Mannucci PM (2008) Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests. Haematologica 93:1256–1259CrossRefPubMed
26.
Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, Mannucci PM (2005) Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 41:553–558CrossRefPubMed
27.
Bevers EM, Comfurius P, Zwaal RF (1991) Platelet procoagulant activity: physiological significance and mechanisms of exposure. Blood Rev 5:146–154CrossRefPubMed
28.
Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell’Era A, Fabris F, Salerno F, Mannucci PM (2006) Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 44:440–445CrossRefPubMed
29.
Bosch J, Thabut D, Bendtsen F, D’Amico G, Albillos A, Gonzalez Abraldes J, Fabricius S, Erhardtsen E, de Franchis R, European Study Group on rFVIIa in UGI Haemorrhage (2004) Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 127:1123–1130CrossRefPubMed
30.
Lodge JP, Jonas S, Jones RM, Olausson M, Mir-Pallardo J, Soefelt S, Garcia-Valdecasas JC, McAlister V, Mirza DF, rFVIIa OLT Study Group (2005) Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 11:973–979CrossRefPubMed
31.
Planinsic RM, van der Meer J, Testa G, Grande L, Candela A, Porte RJ, Ghobrial RM, Isoniemi H, Schelde PB, Erhardtsen E, Klintmalm G, Emre S (2005) Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 11:895–900CrossRefPubMed
32.
McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH, TPL102357 Study Group (2007) Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 357:2227–2236CrossRefPubMed
33.
Tripodi A, Primignani M, Chantarangkul V, Viscardi Y, Dell’Era A, Fabris FM, Mannucci PM (2009) The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters. Thromb Res 124:132–136CrossRefPubMed
34.
35.
Amitrano L, Brancaccio V, Guardascione MA, Margaglione M, Iannaccone L, D’Andrea G, Marmo R, Ames PR, Balzano A (2000) Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 31:345–348CrossRefPubMed
36.
Saliola M, Lorenzet R, Ferro D, Basili S, Caroselli C, Santo AD, Sallese M, Violi F (1998) Enhanced expression of monocyte tissue factor in patients with liver cirrhosis. Gut 43:428–432PubMedCrossRef
37.
Søgaard KK, Horváth-Puhó E, Grønbaek H, Jepsen P, Vilstrup H, Sørensen HT (2009) Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 104:96–101CrossRefPubMed
38.
Rijken DC, Lijnen HR (2009) New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost 7:4–13CrossRefPubMed
39.
Lisman T, Leebeek FW, Mosnier LO, Bouma BN, Meijers JC, Janssen HL, Nieuwenhuis HK, De Groot PG (2001) Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 121:131–139CrossRefPubMed
40.
Colucci M, Binetti BM, Branca MG, Clerici C, Morelli A, Semeraro N, Gresele P (2003) Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 38:230–237CrossRefPubMed
41.
Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD (2009) American Association for the Study of Liver Diseases. Liver biopsy. Hepatology 49:1017–1044CrossRefPubMed
Metadata
Title
Abnormalities of hemostasis and bleeding in chronic liver disease: the paradigm is challenged
Authors
Armando Tripodi
Massimo Primignani
Pier Mannuccio Mannucci
Publication date
01-02-2010
Publisher
Springer Milan
Published in
Internal and Emergency Medicine / Issue 1/2010
Print ISSN: 1828-0447
Electronic ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-009-0302-z

Other articles of this Issue 1/2010

Internal and Emergency Medicine 1/2010 Go to the issue

Editor's Page

Breaking news for the fifth year of Internal and Emergency Medicine

IM - Original

A comparison amongst three rapid urease tests to diagnose Helicobacter pylori infection in 375 consecutive dyspeptic

CE - Letter to the Editor

Hepcidin mutation in a β-thalassemia major patient with persistent severe iron overload despite chelation therapy

CE - Medical Illustration

Anomalous origin of circumflex arteries evaluated with MDCT

EM - Original

Clinical, historical and diagnostic findings associated with right ventricular dysfunction in patients with central and non-massive pulmonary embolism

CE - Medical Illustration

Tibial intercondylar eminence fractures in adults
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits