Heparin Like Effect in Acute Variceal Bleeding

Assessment of Coagulation Profile and Role of Endogenous Heparinoids in SIRS and Sepsis in Acute Variceal Bleeding in Cirrhosis

This study attempts to clarify the pathophysiology of haemostasis in relation to the evidence of sepsis in liver disease, and compares the accuracy of various available laboratory tests in assessment of these patients. Further research is needed for proper understanding of the influence of sepsis on coagulation disorders in acute variceal bleeding in cirrhosis, to correctly identify the type and optimal quantity of blood product requirement in at risk patients.

Thromboelastography (TEG) /Sonoclot has been proposed as a superior tool to rapidly diagnose and help guide resuscitation with blood products. Secondly, the study of derangement in coagulopathy after the onset of sepsis is of paramount importance because of increased mortality after the onset of sepsis. In the present study, patients with cirrhosis who present with acute variceal bleeding, will be included in the study cohort, and will undergo a baseline diagnostic workup as described. They will be followed for development of any signs of infection after hospitalization. Then the effect of sepsis on their coagulation and thrombin generation response swill be assessed. Thus the effect of sepsis on the progression and outcome of coagulopathy in patients with acute variceal bleeding will be studied.

Study Overview

• Status: Recruiting
• Conditions: Coagulation Disorder; Cirrhosis, Liver; Variceal Hemorrhage
• Intervention / Treatment: Diagnostic test: SONOCLOT, coagulation factor assays for VIII/X, XIII, TPA/ PAI

• Study Type: Observational
• Enrollment (Anticipated): 75

Contacts and Locations

• Study Contact: Name: Madhumita Premkumar, MD DM; Phone Number: 01722756344; Email: drmadhumitap@gmail.com

Study Locations

• India
  • Choose Any State/Province
    • Chandigarh, Choose Any State/Province, India, 160012
      • Recruiting
      • Postgraduate Institute of Medical Education and Research
      • Contact: Madhumita Premkumar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cirrhosis with acute variceal bleeding

Description

Inclusion Criteria:

• Age 18-65 years
• Cirrhosis with acute variceal bleeding.

Exclusion Criteria:

• Patients with evidence of sepsis at presentation.
• Current therapy: Recent blood or blood component transfusion in the last 2 weeks.
• HIV positive/ AIDS patients
• Patients requiring antiplatelet therapy,
• Renal insufficiency requiring dialysis
• Active malignancy within the last 5 years
• Patient with other neurological disease and metabolic disorders, unbalanced heart failure and/or respiratory failure or end-stage renal disease
• Administration of anticoagulants, antifibrinolytics,
• Not willing to participate in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cirrhosis with variceal bleeding; Coagulation factor assays and heparinase treated SONOCLOT at Days 0,3, and 7	Diagnostic test: SONOCLOT, coagulation factor assays for VIII/X, XIII, TPA/ PAI; Coagulation assessment using heparinase treated SONOCLOT
Cirrhosis without Bleeding; Control group of 25 subjects	Diagnostic test: SONOCLOT, coagulation factor assays for VIII/X, XIII, TPA/ PAI; Coagulation assessment using heparinase treated SONOCLOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Generation of Endogenous Heparinoids	Change in SONOCLOT values- global and heparinase treated	7 days
Change in plasma levels of Specific Coagulation Factors -VIII, X, XIII, TPA and PAI	Specific factor assessment	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of sonoclot parameters- ACT, PF and Peak amplitude in predicting blood product utilization	blood transfusion requirements	7 Days

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Study Chair: RK Dhiman, MD DM, Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Premkumar M, Mehtani R, Kulkarni AV, Duseja AK, De A, Taneja S, Singh V, Verma N, Ahluwalia J, Kajal K, Divyaveer S, Roy A, Gandotra A, Kalson N, Kekan K, Kaur H, Kaur H. Association of Heparin-Like Effect, Factor VII/XIII Deficiency and Fibrinolysis with Rebleeding Risk in Cirrhosis with Acute Variceal Bleeding. Dig Dis Sci. 2022 Aug 19:1-17. doi: 10.1007/s10620-022-07656-9. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 28, 2019
• First Posted (Actual): October 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 26, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: variceal bleeding; thromboelastography
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Liver Diseases; Hemorrhagic Disorders; Fibrosis; Hemostatic Disorders; Blood Coagulation Disorders; Hemorrhage; Liver Cirrhosis
• Other Study ID Numbers: INT/IEC/2019/001615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No