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Global Coagulation Assessment in Portal Vein Thrombosis and Budd-Chiari Syndrome (Liv-Thrombus)

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ClinicalTrials.gov Identifier: NCT05123326
Recruitment Status : Recruiting
First Posted : November 17, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
Madhumita Premkumar, Postgraduate Institute of Medical Education and Research

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]


Condition or disease Intervention/treatment
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 Diagnostic Test: Rotational thromboelastometry Diagnostic Test: Genetic tests for Thrombophilia Diagnostic Test: ELISA tests/ Functional assays

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.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : October 15, 2021
Estimated Primary Completion Date : April 15, 2024
Estimated Study Completion Date : October 15, 2024


Group/Cohort Intervention/treatment
PVT
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
Diagnostic Test: Rotational thromboelastometry
ROTEM/ Sonoclot tests will be done in all patients at enrolment and after initiating anticoagulation in those who are eligible for the same.
Other Name: Global coagulation test

Diagnostic Test: Genetic tests for Thrombophilia
Tests for JAK2 mutation, CAL R mutation and Factor V Leiden mutation will be done.

Diagnostic Test: ELISA tests/ Functional assays
Antithrombin III, Protein C, Protein S, Factor VIII, VWF using commercial assays

HVOTO
Occlusion of two or more hepatic veins. 100 patients
Diagnostic Test: Rotational thromboelastometry
ROTEM/ Sonoclot tests will be done in all patients at enrolment and after initiating anticoagulation in those who are eligible for the same.
Other Name: Global coagulation test

Diagnostic Test: Genetic tests for Thrombophilia
Tests for JAK2 mutation, CAL R mutation and Factor V Leiden mutation will be done.

Diagnostic Test: ELISA tests/ Functional assays
Antithrombin III, Protein C, Protein S, Factor VIII, VWF using commercial assays




Primary Outcome Measures :
  1. Clinical presentation [ Time Frame: At enrolment ]
    Number of participants with clinical and imaging evidence of PVT and HVOTO in our patient population

  2. Clinical presentation- Extent of disease [ Time Frame: At enrolment ]
    Grading of PVT and HVOTO in our patient population

  3. Occurrence of new thrombotic complications [ Time Frame: At enrolment-3 years ]
    Description of new sites of thrombosis spectrum of PVT and HVOTO in our patient population

  4. Occurrence of all thrombotic complications after anticoagulation [ Time Frame: At enrolment-3 years ]
    Description of new sites of thrombosis spectrum of PVT and HVOTO after anticoagulation

  5. Comparison of performance of standard coagulation tests vs. global coagulation tests to determine the hypercoagulable defect [ Time Frame: At enrolment ]
    PT aPTT INR

  6. Comparison of performance of global coagulation tests to determine the hypercoagulable defect [ Time Frame: At enrolment ]
    ROTEM/Sonoclot


Secondary Outcome Measures :
  1. Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO [ Time Frame: At enrolment ]
    JAK2, CALR, Factor V Leiden mutation

  2. Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO [ Time Frame: At enrolment ]
    CALR mutation test

  3. Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO [ Time Frame: At enrolment ]
    Factor V Leiden mutation

  4. Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO [ Time Frame: At enrolment ]
    JAK2 mutation test

  5. Occurrence of new hemorrhagic complications [ Time Frame: At enrolment-3 years ]
    Sites of bleeding in patients who are not on anticoagulation

  6. Occurrence of new hemorrhagic complications in anticoagulated patients [ Time Frame: At enrolment-3 years ]
    Sites of bleeding in patients who are on anticoagulation


Biospecimen Retention:   Samples Without DNA
Blood and serum samples for thrombophilia evaluation.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
All patients with PVT and HVOTO fitting the inclusion criteria will be prospectively enrolled in the study
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05123326


Contacts
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Contact: Madhumita Prem Kumar, MD DM 0172-2754777 drmadhumitap@gmail.com
Contact: Harmanpreet Kaur Kaur, MSc 0172-2754777 harmandhaliwal635@yahoo.com

Locations
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India
Postgraduate Institute of Medical Education and Research Recruiting
Chandigarh, Choose Any State/Province, India, 160012
Contact: Madhumita Premkumar, MD DM       drmadhumitap@gmail.com   
Contact: Harmanpreet Kaur, MSc    0172-2754777      
Sub-Investigator: Harmanpreet Kaur Kaur, MSc         
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Principal Investigator: Madhumita Premkumar, MD DM Postgraduate Institute of Medical Education and Research
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Responsible Party: Madhumita Premkumar, Associate Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT05123326    
Other Study ID Numbers: PGI/IEC/2021/001451
First Posted: November 17, 2021    Key Record Dates
Last Update Posted: November 17, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension, Portal
Budd-Chiari Syndrome
Thrombosis
Embolism
Venous Thrombosis
Hemostatic Disorders
Blood Coagulation Disorders
Vascular Diseases
Cardiovascular Diseases
Embolism and Thrombosis
Liver Diseases
Digestive System Diseases
Hematologic Diseases
Hemorrhagic Disorders