Global Coagulation Assessment in Portal Vein Thrombosis and Budd-Chiari Syndrome

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. \[13\]

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

Interventions

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.

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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh

  lead OTHER

Principal Investigators

• Madhumita Premkumar, MD DM · Post Graduate Institute of Medical Education and Research, Chandigarh

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-15

Primary Completion

2024-10-15

Completion

2024-10-15

Countries

• India

Study Locations