Project details

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Current and past use of anticoagulants in cirrhosis

Keywords:
thrombosis anticoagulants cirrhosis

Researchers:
Drs. S. Bos
Dr. T.C.M.A. Schreuder

Nature of the research:
This research will focus on the past and current prescription behaviour of physicians concerning anticoagulants in patients with cirrhosis. Besides, the ex vivo potency of the given anticoagulants will be determined by thrombin generation.

Fields of study:
laboratory medicine gastroenterology vascular medicine

Background / introduction
Patients with cirrhosis have a delicate hemostatic balance, which can lead to both bleeding and thrombotic events. The incidence of thrombotic events is higher than previously appreciated, whereas antithrombotic treatment in this specific population is challenging. Specifically, dosing and monitoring of traditional anticoagulants, such as vitamin K antagonists (VKA) and low molecular weight heparin (LMWH), is difficult. The international normalized ratio (INR) is frequently prolonged in patients with cirrhosis, which makes monitoring of VKA troublesome. Treatment with LMWH is inconvenient through its subcutaneous administration. The direct oral anticoagulants lack these disadvantages, but clinical experience in patients with cirrhosis is minimal. In the absence of evidence-based guidelines for patients with cirrhosis antithrombotic treatment is at the discretion of the treating physician.
Research question / problem definition
1. To investigate the ex vivo efficacy of prophylactic and therapeutic anticoagulants administered in daily clinical practice.
2. To observe and describe the past and current prescription behaviour of treating physicians
Workplan
The data for the first research objective wil be gathered prospectively by drawing blood samples before and after initiation of anticoagulation. The ex vivo potentcy will then be performed by determining the thrombin generation time in a research laboratory.
The data for the second objective will be gathered by retrospective chart review of all known cirrhotic patients from the Hepatology outpatient clinic. Past use of anticoagulants and past bleeding or thrombotic events need to be documented. The student will mainly be involved in the proces for the second objective, but can participate in the prospective study as well.
References
(1) Lisman T et al. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010-8-12;116(6):878-85.
(2) Tripodi A. The coagulopathy of chronic liver disease. N Engl J Med 2011-7-14;365(2):147-56.
(3) Sogaard KK, Horvath-Puho E, Gronbaek H, Jepsen P, Vilstrup H, Sorensen HT. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009 Jan;104(1):96-101.
(4) Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012 Nov;143(5):1253-60.e1-4.
(5) Lisman T et al. Established and new-generation antithrombotic drugs in patients with cirrhosis - possibilities and caveats. J Hepatol 2013-8;59(2):358-66.
(6) Amitrano L et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010-7;44(6):448-51.
(7) Intagliata NM et al. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver International 2014-1;34(1):26-32.
(8) Shatzel J et al. Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. Journal of Thrombosis and Haemostasis 2015-7;13(7):1245-53.
(9) Gómez Cuervo Covadonga C et al. Efficacy and safety of the use of heparin as thromboprophylaxis in patients with liver cirrhosis: a systematic review and meta-analysis. Thromb Res 2013-10;132(4):414-9.
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