Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 1;32(1):1-7.
doi: 10.1097/MBC.0000000000000966.

Preservation of thrombin generation in cirrhosis despite abnormal results of international normalized ratio: implications for invasive procedures

Caroline M Ferreira  1 , Tania R F Rocha  2 , Evandro O Souza  1 , Flair J Carrilho  1 , Elbio A d'Amico  2 , Alberto Q Farias  1
Affiliations

Preservation of thrombin generation in cirrhosis despite abnormal results of international normalized ratio: implications for invasive procedures

Caroline M Ferreira et al. Blood Coagul Fibrinolysis. .

Abstract

Thrombin generation is normal or elevated in patients with cirrhosis when tested in the presence of thrombomodulin, the activator of the main natural anticoagulant protein C. However, the relationship between thrombin generation with bleeding has been little explored in literature. 97 Consecutive patients with cirrhosis were prospectively included (58 men; 54 ± 10 years) and divided into two groups international normalized ratio (INR) less than 1.5 (n = 72) or INR at least 1.5 (n = 25). 46 Healthy individuals were tested as controls. Endogenous thrombin potential (ETP) was measured without and with the addition of thrombomodulin. ETP measured without thrombomodulin was reduced in patients with cirrhosis when compared with controls, but no significant difference was found between the INR less than 1.5 and INR at least 1.5 groups (1250 ± 315.7 versus 1186 ± 238 nmol/l × min; P = 0.3572). After the addition of thrombomodulin, both groups generated thrombin comparable with controls (INR ≥ 1.5: 965.9 ± 232.3; INR < 1.5: 893.0 ± 368.6; controls: 915.0 ± 458 nmol/l × min). 80% of patients had high ETP without/with thrombomodulin ratio, demonstrating the resistance to the anticoagulant action of thrombomodulin for both groups. This was more marked in the INR at least 1.5 group (0.81 ± 0.1 versus 0.69 ± 0.2; P = 0.0042). Postligation of esophageal varices bleeding occurred in 5.2% of patients (INR < 1.5, n = 3; INR ≥ 1.5, n = 2), all of them with ETP without/with thrombomodulin ratio ranging from 0.72 to 0.90 (controls 0.57 ± 0.21). This study confirms that thrombin generation in the presence of thrombomodulin was normal in most patients with cirrhosis, including those with high INR value, but did not correlate with postligation of esophageal varices bleeding.

PubMed Disclaimer

References

    1. Tripodi A, Mannucci PM. Mechanisms of disease. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365:147–156.
    1. Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR. A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII. Blood 2014; 123:3706–3713.
    1. Shi Q, Fahs SA, Kuether EL, Cooley BC, Weiler H, Montgomery RR. Targeting FVIII expression to endothelial cells regenerates a releasable pool of FVIII and restores hemostasis in a mouse model of hemophilia A. Blood 2010; 116:3049–3057.
    1. Tripodi A, Primignani M, Chantarangkul V, Dell’Era A, Clerici M, de Franchis R, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137:2105–2111.
    1. Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell’Era A, Fabris F, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44:440–445.

LinkOut - more resources