Thromb Haemost 2010; 104(04): 741-749
DOI: 10.1160/TH10-01-0040
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Comparative study of coagulation and thrombin generation in the portal and jugular plasma of patients with cirrhosis

Bénédicte Delahousse*
1   Department of Haematology-Haemostasis, University Hospital of Tours, France
,
Valérie Labat-Debelleix*
2   Department of Gastroenterology and Hepatology, University Hospital of Tours, France
,
Loic Decalonne
1   Department of Haematology-Haemostasis, University Hospital of Tours, France
,
Louis d’Alteroche
2   Department of Gastroenterology and Hepatology, University Hospital of Tours, France
,
Jean-Marc Perarnau
2   Department of Gastroenterology and Hepatology, University Hospital of Tours, France
,
Yves Gruel
1   Department of Haematology-Haemostasis, University Hospital of Tours, France
3   U618 Inserm “Proteases et vectorisation pulmonaires”, University François Rabelais, Tours, France
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 15. Januar 2010

Accepted after major revision: 29. Mai 2010

Publikationsdatum:
24. November 2017 (online)

Summary

Portal vein thromboses are frequent in cirrhotic patients and may be favoured by hypercoagulability in the splanchnic venous system. The coagulation balance and thrombin generation (TG) were evaluated in platelet-free plasma obtained from portal and systemic blood samples in 28 cirrhotic patients while undergoing transjugular intrahepatic porto-systemic shunt. TG assay (TGA) was performed with all samples from cirrhotic patients and with plasma samples from 14 healthy controls, with varying concentrations of tissue factor and phospholipids, with or without thrombomodulin. Screening tests and specific assays were also performed and activated partial thromboplastin time was shorter in portal plasma samples with higher FVIII and lower protein C levels, well correlated with Child-Pugh scores, and higher D-dimers and F1+2 levels However, all TGA parameters were similar in portal and jugular samples, possibly due in part to similar concentrations of factor II and antithrombin in these two sites of plasma sampling. TGA showed lower thrombin peaks and endogenous thrombin potential values in cirrhotic plasma compared to those of healthy controls. Importantly, a resistance to thrombomodulin that well correlated with factor VIII and PC levels, was evidenced in all samples from patients with cirrhosis, and was more significant in those from severely affected cases. This study therefore supports the existence of a relative hypercoagulability in the portal vein of cirrhotic patients that is likely due to protein C/S deficiency and to high FVIII levels.

* These authors equally contributed to this study.


 
  • References

  • 1 Boks AL, Brommer EJ, Schalm SW. et al. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage.. Hepatology 1986; 6: 79-86.
  • 2 Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research.. J Hepatol 2007; 46: 727-733.
  • 3 Hemker HC, Giesen PL, Ramjee M. et al. The thrombogram: monitoring thrombin generation in platelet-rich plasma.. Thromb Haemost 2000; 83: 589-591.
  • 4 Hemker HC, Wielders S, Kessels H. et al. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential.. Thromb Haemost 1993; 70: 617-624.
  • 5 Baglin T. The measurement and application of thrombin generation.. Br J Haematol 2005; 130: 653-661.
  • 6 Tripodi A, Legnani C, Chantarangkul V. et al. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism.. J Thromb Haemost 2008; 6: 1327-1333.
  • 7 Besser M, Baglin C, Luddington R. et al. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study.. J Thromb Haemost 2008; 6: 1720-1725.
  • 8 Couturaud F, Duchemin J, Leroyer C. et al. Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden. A pilot study.. Thromb Haemost 2008; 99: 223-228.
  • 9 Segers O, van Oerle R, ten Cate H. et al. Thrombin generation as an intermediate phenotype for venous thrombosis.. Thromb Haemost 2010; 103: 114-122.
  • 10 Dargaud Y, Beguin S, Lienhart A. et al. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B.. Thromb Haemost 2005; 93: 475-480.
  • 11 Schols SE, van der Meijden PE, van Oerle R. et al. Increased thrombin generation and fibrinogen level after therapeutic plasma transfusion: relation to bleeding.. Thromb Haemost 2008; 99: 64-70.
  • 12 Salvagno GL, Astermark J, Lippi G. et al. Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?. Haemophilia 2009; 15: 290-296.
  • 13 Tripodi A, Salerno F, Chantarangkul V. et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests.. Hepatology 2005; 41: 553-558.
  • 14 Tripodi A, Primignani M, Chantarangkul V. et al. Thrombin generation in patients with cirrhosis: the role of platelets.. Hepatology 2006; 44: 440-445.
  • 15 Jacobi D, de Muret A, Arbeille B. et al. Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal hepatic fibrosis.. Eur J Gastroenterol Hepatol 2006; 18: 549-551.
  • 16 Rossle M, Haag K, Ochs A. et al. The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding.. N Engl J Med 1994; 330: 165-171.
  • 17 Pugh RN, Murray-Lyon IM, Dawson JL. et al. Transection of the oesophagus for bleeding oesophageal varices.. Br J Surg 1973; 60: 646-649.
  • 18 Ripoll L, Paulin D, Thomas S. et al. Multiplex PCR-mediated site-directed muta-genesis for one-step determination of factor V Leiden and G20210A transition of the prothrombin gene.. Thromb Haemost 1997; 78: 960-961.
  • 19 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma.. Pathophysiol Haemost Thromb 2003; 33: 4-15.
  • 20 Mayer LD, Hope MJ, Cullis PR. Vesicles of variable sizes produced by a rapid extrusion procedure.. Biochim Biophys Acta 1986; 858: 161-168.
  • 21 Dargaud Y, Trzeciak MC, Bordet JC. et al. Use of calibrated automated thrombinography +/- thrombomodulin to recognise the prothrombotic phenotype.. Thromb Haemost. 2006; 96: 562-567.
  • 22 Tchaikovski SN, van Vliet HA, Thomassen MC. et al. Effect of oral contraceptives on thrombin generation measured via calibrated automated thrombography.. Thromb Haemost 2007; 98: 1350-1356.
  • 23 Haidl H, Cimenti C, Leschnik B. et al. Age-dependency of thrombin generation measured by means of calibrated automated thrombography (CAT).. Thromb Haemost 2006; 95: 772-775.
  • 24 Dielis AW, Castoldi E, Spronk HM. et al. Coagulation factors and the protein C system as determinants of thrombin generation in a normal population.. J Thromb Haemost 2008; 6: 125-131.
  • 25 Al Dieri R, Peyvandi F, Santagostino E. et al. The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding.. Thromb Haemost 2002; 88: 576-582.
  • 26 Duchemin J, Pan-Petesch B, Arnaud B. et al. Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma.. Thromb Haemost 2008; 99: 767-773.
  • 27 Hollestelle MJ, Geertzen HG, Straatsburg IH. et al. Factor VIII expression in liver disease.. Thromb Haemost 2004; 91: 267-275.
  • 28 Martinelli I, Primignani M, Aghemo A. et al. High levels of factor VIII and risk of extra-hepatic portal vein obstruction.. J Hepatol 2009; 50: 916-922.
  • 29 Machlus KR, Colby EA, Wu JR. et al. Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram.. Thromb Haemost 2009; 102: 936-944.
  • 30 Tripodi A, Primignani M, Chantarangkul V. et al. An imbalance of pro- vs anticoagulation factors in plasma from patients with cirrhosis.. Gastroenterology 2009; 137: 2105-2111.
  • 31 Reverdiau-Moalic P, Delahousse B, Body G. et al. Evolution of blood coagulation activators and inhibitors in the healthy human fetus.. Blood. 1996; 88: 900-906.
  • 32 Zocco MA, Di Stasio E, De Cristofaro R. et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.. J Hepatol 2009; 51: 682-689.
  • 33 Fimognari FL, Violi F. Portal vein thrombosis in liver cirrhosis.. Intern Emerg Med 2008; 3: 213-218.
  • 34 Violi F, Ferro D, Basili S. et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients.. Thromb Haemost 1997; 77: 44-47.
  • 35 Hemker HC, Al Dieri R, De Smedt E. et al. Thrombin generation, a function test of the haemostatic-thrombotic system.. Thromb Haemost 2006; 96: 553-561.