Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic

NCT ID: NCT03580577

Last Updated: 2018-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-09-01

Study Completion Date

2019-09-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Liver Cirrhosis Venous Thromboembolism

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Cirrhotic with venous thromboembolism

cirrhotic patients with a venous thromboembolic event (including deep venous thrombosis, pulmonary embolism, acute non-malignant portal vein thrombosis, splenic vein, inferior vena cava thrombosis or mesenteric vascular occlusion).

Each patient will subjected to through history taking and careful examination to detect and risk factors also laboratory work to detect thrombocytopenia, disease severity, coagulation status thrombelastography before starting anticoagulants.

* Patients will start treatment with anticoagulants therapy after liaise with the specialized physician.
* Protein C, protein S and antithrombin III level will be assessed 3 months after the acute thrombotic event and 1 month of vitamin K antagonist (VKA) withdrawal.

thromboelastography

Intervention Type DEVICE

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

Cirrhotic without venous thromboembolism

cirrhotic patients without any thrombotic events Each patient will subjected to through history taking and careful examination to detect and risk factors.

\- Protein C, protein S and antithrombin III level will be assessed at baseline.

No interventions assigned to this group

Interventions

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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

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Ahmed Radwan Riad

Assistant lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mohamed Abdel Sabour Mohamed Mekky

Role: STUDY_DIRECTOR

Assiut University

Locations

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Assiut university

Asyut, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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Ahmed Radwan Riad

Role: CONTACT

+2 01126435001

Mohamed Abdel Sabour Mohamed Mekky

Role: CONTACT

References

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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.

Reference Type BACKGROUND
PMID: 18443906 (View on PubMed)

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. doi: 10.1111/j.1572-0241.2006.00588.x.

Reference Type BACKGROUND
PMID: 16863556 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28088580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19706293 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23583273 (View on PubMed)

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. doi: 10.1002/hep.21266.

Reference Type BACKGROUND
PMID: 16871542 (View on PubMed)

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. doi: 10.1002/hep.20569.

Reference Type BACKGROUND
PMID: 15726661 (View on PubMed)

van Wijngaarden A, van den Besselaar AM, Bertina RM. Thrombomodulin activity in commercial thromboplastin preparations. Thromb Res. 1986 Aug 1;43(3):265-74. doi: 10.1016/0049-3848(86)90146-5.

Reference Type BACKGROUND
PMID: 3016943 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27470055 (View on PubMed)

HARTERT H. [Thrombelastography, a method for physical analysis of blood coagulation]. Z Gesamte Exp Med. 1951;117(2):189-203. No abstract available. Undetermined Language.

Reference Type BACKGROUND
PMID: 14836887 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 27311154 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 22670837 (View on PubMed)

Other Identifiers

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Liver cirrhosis and thrombosis

Identifier Type: -

Identifier Source: org_study_id

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