Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic

Liver Cirrhosis Clinical Trial

Official title:

Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic Patients: A Hospital Based Prospective Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03580577
• Other study ID #: Liver cirrhosis and thrombosis
• Status: Not yet recruiting
• Start date: September 1, 2018
• Est. completion date: September 1, 2019

Study information

• Verified date: July 2018
• Source: Assiut University
• Contact: Ahmed Radwan Riad
• Phone: +2 01126435001
• Email: dr.radwan1988[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

patient with liver cirrhosis was supposed to have autoanticoagulation which approved to be wrong, with absence of conventional method to detect all abnormalities in coagulation state. Thromboelastography (TEG) give a broad picture for the coagulation defects.

In addition to that no guidelines prescribed anticoagulants for venous thromboembolism in cirrhotic, so the investigators will do a study to demonstrate frequency and risk factors for acute venous thromboembolism in cirrhotic patients, find a conventional laboratory method and test TEG to assess risk of thrombosis in cirrhotic patients.Also, to validate current algorithm for use of anticoagulant and antiplatelet for thromboembolism for non cirrhotic in cirrhotic patients.

Description:

Nowadays, the term "autoanticoagulated" ,which prescribed coagulopathy state in chronic liver disease (CLD) patients due to impaired synthesis of coagulation factors and elevated international normalized ratio(INR), has been approved to be wrong and those patients are liable for venous thromboembolism (VTE) with 0.5% - 6.3% incidence of deep venous thrombosis (DVT) and pulmonary thromboembolism (PE) among cirrhotic patients.

This may be explained by normal or even increased production of factor VIII and von Willebrand factor, enhanced thrombin activity and Low level of protein C, protein S and antithrombin III due to impaired liver synthesis, other risk factor include sedentary lifestyle, fractures, immobility, hospitalization, elevated estrogen levels, surgery, concomitant disease states and cancer, damaged vasculature that increases inflammation, and sluggish splanchnic blood flow, which are all common in those patients.

Absence of gold standard estimation for hypercoagulability in cirrhotic patients, is a big problem. During measurement of conventional parameters such as international normalized ratio (INR) or partial thromboplastin time, reagents used to measure the prothrombin time do not contain thrombomodulin on which protein C depend for activation, so it does not adequately reflect reduced levels protein C. Thromboelastography a device that has the ability to measure whole blood coagulation cascade including platelet function, It can be used to monitor coagulation status before liver transplantation operation to properly identify and treat coagulation abnormalities.

No worldwide guidelines is established neither for management nor prophylaxis of VTE in cirrhotic patients, this may be due to safety concerns regarding the risk of bleeding related to anticoagulant drugs when used in people with advanced liver disease, especially if there is significant thrombocytopenia, and/or the presence of varices.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 1, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• all cirrhotic patient who developed venous thromboembolic events

• written informed consent (patient or nearest relative )

Exclusion Criteria:

• Patient with chronic thromboembolic event ( e.g. chronic pulmonary embolism, chronic portal vein thrombosis).

• patients on antiplatelets or anticoagulants.

• Patients with end stage kidney, heart or lung diseases

• Pregnant.

• Cirrhotic patients on control group who develop an acute thromboembolic event during the study period will be excluded and shifted to the case group

Related Conditions & MeSH terms

• Liver Cirrhosis
• Thromboembolism
• Venous Thromboembolism

Intervention

Device:
• thromboelastography
thromboelastography will assess all coagulation abnormalities including platelets function in cirrhotic group with venous thromboembolism , and guide us about is there increased thrombosis risk or not, for that a fresh blood sample will be withdrawn from each patient before starting any treatment

Locations

Country	Name	City	State
Egypt	Assiut university	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (12)

Collins S, MacIntyre C, Hewer I. Thromboelastography: Clinical Application, Interpretation, and Transfusion Management. AANA J. 2016 Apr;84(2):129-34. — View Citation

Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017 Jun;66(6):1313-1326. doi: 10.1016/j.jhep.2017.01.006. Epub 2017 Jan 12. Review. — View Citation

Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008 Nov;53(11):3012-7. doi: 10.1007/s10620-008-0265-3. Epub 2008 Apr 29. — View Citation

HARTERT H. [Thrombelastography, a method for physical analysis of blood coagulation]. Z Gesamte Exp Med. 1951;117(2):189-203. Undetermined Language. — View Citation

MacIvor D, Rebel A, Hassan ZU. How do we integrate thromboelastography with perioperative transfusion management? Transfusion. 2013 Jul;53(7):1386-92. doi: 10.1111/j.1537-2995.2012.03728.x. Epub 2012 Jun 7. — View Citation

Northup PG, McMahon MM, Ruhl AP, Altschuler SE, Volk-Bednarz A, Caldwell SH, Berg CL. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006 Jul;101(7):1524-8; quiz 1680. — View Citation

Tripodi A, Primignani M, Braham S, Chantarangkul V, Clerici M, Moia M, Peyvandi F. Coagulation parameters in patients with cirrhosis and portal vein thrombosis treated sequentially with low molecular weight heparin and vitamin K antagonists. Dig Liver Dis. 2016 Oct;48(10):1208-13. doi: 10.1016/j.dld.2016.06.027. Epub 2016 Jul 1. — View Citation

Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell'Era A, Fabris F, Salerno F, Mannucci PM. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006 Aug;44(2):440-5. — View Citation

Tripodi A, Primignani M, Chantarangkul V, Dell'Era A, Clerici M, de Franchis R, Colombo M, Mannucci PM. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-11. doi: 10.1053/j.gastro.2009.08.045. Epub 2009 Aug 23. — View Citation

Tripodi A, Primignani M, Lemma L, Chantarangkul V, Mannucci PM. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol. 2013 Aug;59(2):265-70. doi: 10.1016/j.jhep.2013.03.036. Epub 2013 Apr 11. — View Citation

Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, Mannuccio Mannucci P. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005 Mar;41(3):553-8. — View Citation

van Wijngaarden A, van den Besselaar AM, Bertina RM. Thrombomodulin activity in commercial thromboplastin preparations. Thromb Res. 1986 Aug 1;43(3):265-74. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of recanalization of thrombosed vessel	Efficacy of anticoagulants describe its ability to prevent further thrombosis and restore patency of thrmobosed vessel	24 weeks from baseline
Secondary	detect safety of anticoagulants in cirrhotic	Occurrence of any bleeding event while on anticoagulants therapy	During treatment period wither 12 or 24 weeks from starting therapy
Secondary	Correlate thromboelastography results with hypercoagluable state in cirrhotic patients with venous thromboembolism	Changes in r, k and MA- TEG parameters in cirrhotic patients with venous thromboembolism	1 day