Global Coagulation Assessment in Portal Vein Thrombosis and Budd-Chiari Syndrome
- Conditions
- Hepatic Vein ThrombosesHepatic Venous Outflow ObstructionPortal Vein ThrombosisPortal Vein OcclusionCALR Gene MutationPortal Vein EmbolismJAK2 MutationPortal Hypertension, NoncirrhoticProthrombin G20210AAnticoagulants and Bleeding Disorders
- Interventions
- Diagnostic Test: Rotational thromboelastometryDiagnostic Test: Genetic tests for ThrombophiliaDiagnostic Test: ELISA tests/ Functional assays
- Registration Number
- NCT05123326
- Lead Sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Brief Summary
Portal vein thrombosis is defined as partial or complete occlusion of the portal vein lumen by the blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, known as 'portal cavernoma'. \[1,2\] Based on the published literature, 15-25% of patients with cirrhosis have portal vein thrombosis (PVT) \[3\], and 35-50% of patients with hepatocellular carcinoma (HCC) have malignant PVT \[4\] compared to 1-3.8 per 100,000 patients in the general population. \[5\] The reported cumulative incidence of PVT in patients of Child-Pugh A and B is 4.6% and 10.7% at 1 and 5 years respectively with higher incidence among those with decompensated disease or with an underlying hypercoagulable disorder. \[6\]. Similarly, the prevalence of PVT in compensated cirrhosis is around 1% which increases to 8 - 25% in liver transplant (LT) candidates and 40% in patients with hepatocellular carcinoma (HCC) \[7,8\]. Based on the published literature 7-9 % of all chronic liver disease patients have hepatic vein outflow tract obstruction (HVOTO) in the Indian population. \[9\] HVOTO is defined as obstruction to hepatic venous outflow at any site from the right atrium inlet to the small hepatic venules. The Budd-Chiari syndrome (BCS) results from occlusion of one or more hepatic veins (HV) and/or the inferior vena cava (IVC). In the West, the most common cause is HV occlusion by thrombosis. More recent Indian studies have however shown that isolated HV and combined IVC+HV obstruction are now more common. \[10\]
In the post COVID-19 era, there has been great interest in the prothrombotic states associated with the SARS-Cov-2 virus infection, and the adverse effects of some vaccines. \[11\] With the availability of better molecular tests for hypercoagulable states, use of global coagulation tests (GCT) like rotational thromboelastometry (ROTEM), thromboelastography (TEG) and Sonoclot, use of therapeutic procedures like Transjugular intrahepatic portosystemic shunt (TIPS), availability of novel oral anticoagulants (NOAC), the natural course of disease can be changed with good outcomes. \[12\] Standard Coagulation tests (SCTs) like PT, aPTT, and platelet count are not predictive of bleeding or coagulation risk as they exclude the cellular elements of hemostasis and are unable to assess the effect of thrombomodulin and cannot assess the stage of the coagulation pathway which is affected. Global coagulation tests provide dynamic information on the coagulation pathway that is not available from conventional tests. \[13\]
- Detailed Description
Our proposed study is important for the following 4 reasons.
1. SCTs cannot be used to demonstrate the thrombomodulin mediated normal thrombin generation in patients with liver disease, so the monitoring of such patient using global coagulation tests can be validated. The use of point-of-care global coagulation tests like ROTEM and Sonoclot enables us to identify the true prothrombotic and hypocoagulable states which can be used to assess for increased clot strength, clot formation time, and indicate hyperfibrinolysis. The use of conventional tests like prothrombin time, partial thromboplastin time and INR cannot bolster the therapeutic strategy.
2. This study will also help to determine role of global coagulation tests rather than PT/INR /aPTT in monitoring the dose and response of anticoagulants like vitamin K antagonists and novel oral anticoagulants (NOAC) in patients who are on therapeutic anticoagulation for HVOTO/PVT.
3. This study will also help to determine the prevalence and role of CALR, JAK2V617F, factor V Leiden mutations in patients with PVT and HVOTO in our population.
4. We will also be prospectively assessing the rate of thrombophilia complications in the Post COVID-19 era, and the study will generate information regarding new incidence of PVT/HVOTO in those exposed to COVID-19.
Therefore, the current study is the need of the hour, as we intend to assess the relevance of PVT and outcomes, test the genetic predisposition of Indian patients to hyper coagulable states, develop anticoagulation algorithms using NOAC, and determine the true burden on disease in India.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Gender: Either gender
- Age:18 - 65 years of age
- Patient with portal vein thrombosis documented on imaging (USG with color doppler, CECT abdomen and CEMRI abdomen
- Patients who do not consent to the study.
- Patient with pregnancy and lactation
- Patients with a history of blood transfusions in the last two weeks
- Patients who are too sick to undergo screening tests.
- Patients on hemodialysis
- Chronic heart failure and chronic pulmonary or end-stage renal disease
- Patients who are on plasma therapy
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PVT Genetic tests for Thrombophilia Portal Vein Thrombosis (PVT) refers to partial or complete occlusion of the portal vein lumen by a blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, commonly known as 'portal cavernoma.' 240 patients to be recruited HVOTO Genetic tests for Thrombophilia Occlusion of two or more hepatic veins. 100 patients PVT ELISA tests/ Functional assays Portal Vein Thrombosis (PVT) refers to partial or complete occlusion of the portal vein lumen by a blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, commonly known as 'portal cavernoma.' 240 patients to be recruited PVT Rotational thromboelastometry Portal Vein Thrombosis (PVT) refers to partial or complete occlusion of the portal vein lumen by a blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, commonly known as 'portal cavernoma.' 240 patients to be recruited HVOTO ELISA tests/ Functional assays Occlusion of two or more hepatic veins. 100 patients HVOTO Rotational thromboelastometry Occlusion of two or more hepatic veins. 100 patients
- Primary Outcome Measures
Name Time Method Clinical presentation- Extent of disease At enrolment Grading of PVT and HVOTO in our patient population
Occurrence of new thrombotic complications At enrolment-3 years Description of new sites of thrombosis spectrum of PVT and HVOTO in our patient population
Comparison of performance of standard coagulation tests vs. global coagulation tests to determine the hypercoagulable defect At enrolment PT aPTT INR
Clinical presentation At enrolment Number of participants with clinical and imaging evidence of PVT and HVOTO in our patient population
Occurrence of all thrombotic complications after anticoagulation At enrolment-3 years Description of new sites of thrombosis spectrum of PVT and HVOTO after anticoagulation
Comparison of performance of global coagulation tests to determine the hypercoagulable defect At enrolment ROTEM/Sonoclot
- Secondary Outcome Measures
Name Time Method Occurrence of new hemorrhagic complications in anticoagulated patients At enrolment-3 years Sites of bleeding in patients who are on anticoagulation
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO At enrolment JAK2 mutation test
Occurrence of new hemorrhagic complications At enrolment-3 years Sites of bleeding in patients who are not on anticoagulation
Trial Locations
- Locations (1)
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, Choose Any State/Province, India