Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
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
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| 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. |
Outcome Measures
Primary Outcome Measures
- Occurence of recanalization of thrombosed vessel [24 weeks from baseline]
Efficacy of anticoagulants describe its ability to prevent further thrombosis and restore patency of thrmobosed vessel
Secondary Outcome Measures
- detect safety of anticoagulants in cirrhotic [During treatment period wither 12 or 24 weeks from starting therapy]
Occurrence of any bleeding event while on anticoagulants therapy
- Correlate thromboelastography results with hypercoagluable state in cirrhotic patients with venous thromboembolism [1 day]
Changes in r, k and MA- TEG parameters in cirrhotic patients with venous thromboembolism
Eligibility Criteria
Criteria
Inclusion Criteria:
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all cirrhotic patient who developed venous thromboembolic events
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written informed consent (patient or nearest relative )
Exclusion Criteria:
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Patient with chronic thromboembolic event ( e.g. chronic pulmonary embolism, chronic portal vein thrombosis).
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patients on antiplatelets or anticoagulants.
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Patients with end stage kidney, heart or lung diseases
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Pregnant.
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Cirrhotic patients on control group who develop an acute thromboembolic event during the study period will be excluded and shifted to the case group
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Assiut university | Assiut | Egypt |
Sponsors and Collaborators
- Assiut University
Investigators
- Study Director: Mohamed Abdel Sabour Mohamed Mekky, Assiut University
Study Documents (Full-Text)
None provided.More Information
Publications
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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.
- HARTERT H. [Thrombelastography, a method for physical analysis of blood coagulation]. Z Gesamte Exp Med. 1951;117(2):189-203. Undetermined Language.
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- 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.
- 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.
- 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.
- 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.
- 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.
- van Wijngaarden A, van den Besselaar AM, Bertina RM. Thrombomodulin activity in commercial thromboplastin preparations. Thromb Res. 1986 Aug 1;43(3):265-74.
- Liver cirrhosis and thrombosis