Clinical trial NCT05123326: Global Coagulation Assessment in Portal Vein Thrombosis and Budd-Chiari Syndrome
Official title: Prospective Evaluation of Coagulation Status and Thromboelastometry Guided Management of Genetic and Acquired Thrombophilia in Patients With Portal Vein Thrombosis and Budd-Chiari Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatic Vein Thromboses
Hepatic Venous Outflow Obstruction
Portal Vein Thrombosis
Portal Hypertension, Noncirrhotic
Portal Vein Occlusion
Portal Vein Embolism
JAK2 Mutation
CALR Gene Mutation
Prothrombin G20210A
Anticoagulants and Bleeding Disorders
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2021-11-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with PVT and HVOTO fitting the inclusion criteria will be prospectively enrolled in the study

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical presentation
timeFrame: At enrolment
measure: Clinical presentation- Extent of disease
timeFrame: At enrolment
measure: Occurrence of new thrombotic complications
timeFrame: At enrolment-3 years
measure: Occurrence of all thrombotic complications after anticoagulation
timeFrame: At enrolment-3 years
measure: Comparison of performance of standard coagulation tests vs. global coagulation tests to determine the hypercoagulable defect
timeFrame: At enrolment
measure: Comparison of performance of global coagulation tests to determine the hypercoagulable defect
timeFrame: At enrolment
Secondary outcomes:
measure: Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
timeFrame: At enrolment
measure: Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
timeFrame: At enrolment
measure: Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
timeFrame: At enrolment
measure: Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
timeFrame: At enrolment
measure: Occurrence of new hemorrhagic complications
timeFrame: At enrolment-3 years
measure: Occurrence of new hemorrhagic complications in anticoagulated patients
timeFrame: At enrolment-3 years
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
state: Choose Any State/Province
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Madhumita Premkumar, MD DM
role: PRINCIPAL_INVESTIGATOR
References: