Goal-Directed Hemostatic Resuscitation Trial in ACLF Induced Coagulopathy

Patients with acute-on-chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra-hepatic organ failures. The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing.Need for periprocedural blood transfusion is still high in patients with decompensated cirrhosis or ACLF who present with major bleeding. Allogeneic blood transfusion may be detrimental in patients with cirrhosis, due to volume overload and acute lung injury. Viscoelastic testing of global coagulation such as thromboelastometry has been proposed as a superior tool to rapidly diagnose and help guide resuscitation with blood products. In prior studies, we have clarified the pathophysiology of hemostasis in relation to the evidence of sepsis in liver disease and described the accuracy of various available laboratory tests in assessment of these patients. We have described the role of endogenous heparinoids in severe alcoholic hepatitis and the pathogenesis of the coagulation defect in ACLF. We determined the influence of sepsis on coagulation disorders in ACLF patients, to correctly identify the type and optimal quantity of blood product requirement in at risk patients.

Patient with ACLF with variceal bleeding is eligible for the study if one or more of the criteria are met following primary endoscopic intervention.

• Multiple sites of bleed e.g. diffuse mucosal ooze, post EVL ulcers, diffuse portal hypertensive gastropathy, etc which are associated with coagulation dysfunction against a background of portal hypertensive bleeding
• Failure to control bleeding
• Active bleeding on endoscopy with refractory variceal bleeding, need for balloon tamponade or self expandable metal stents (SEMS)
• At the time of bridge therapy to a more definite treatment such as PTFE covered TIPS.

If one of the above criteria is met, then the patient is enrolled provided they meet the criteria below.

Inclusion criteria

• Age 18-65 years
• ACLF, as diagnosed by CANONIC/ APASL criteria .
• Upper gastrointestinal bleeding

Exclusion criteria

• 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