PB0983 - Use of prothrombin complex concentrates in severe liver disease: in vitro dose effects on haemostasis parameters: COPIH Study

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Imen Ben Salah, MD

Hematologist
Service Hématologie Biologique, Hôpital Beaujon (APHP)
Clichy, Ile-de-France, France

Co-Author(s)

MR

Madeleine Rousseaux

Assistant
Service Hématologie Biologique, Hôpital Beaujon (APHP)
Clichy, Ile-de-France, France
Marie-Charlotte BOURRIENNE, PharmD

Assistant
Laboratoire d'Hématologie, AP-HP, Hôpital Bichat Claude-Bernard, Paris, France.
PARIS, Ile-de-France, France
LB

Larbi Boudaoud

Hematologist
Service Hématologie Biologique, Hôpital Beaujon (APHP)
Clichy, Ile-de-France, France
CT

Catherine Trichet

Hematologist
Service Hématologie Biologique, Hôpital Beaujon (APHP)
Clichy, Ile-de-France, France
PR

Pierre-Emmanuel Rautou

Hepatology Specialist
Service d’Hépatologie et de Réanimation Hépato-digestive, Hopital Beaujon (APHP)
Clichy, Ile-de-France, France
FD

François Durand

Hepatology Specialist
Service d’Hépatologie et de Réanimation Hépato-digestive, Hopital Beaujon (APHP)
Clichy, Ile-de-France, France
OR

Olivier Roux

Hepatology Specialist
Service d’Hépatologie et de Réanimation Hépato-digestive, Hopital Beaujon (APHP)
Clichy, Ile-de-France, France
Ed

Emmanuelle de Raucourt

Hematologist
Centre de ressources et compétences des Maladies Hémorragiques Constitutionnelles rares, centre hospitalier de Versailles (André Mignot)
Le chesnay, Ile-de-France, France

Background: Changes in pro- and anti-coagulant pathways are common features in patients with severe liver disease leading to an increased risk of both bleeding and thrombotic complications. Common strategies to manage hemorrhage include fresh frozen plasma, platelets transfusion and prothrombin complex concentrates infusion (PCCs). PCCs offer a good alternative in patients with liver diseases by avoiding large-volume infusion. However, conflicting results have been reported on optimal dosage of PCCs regarding thrombotic risk.

Aims: Hemostasis parameters were evaluated at baseline and, after in vitro addition in whole blood of two doses of PCCs in patients with severe liver diseases (acute liver failure or chronic liver disease).

Methods: PCC (Confidex®, CSL Behring) was added to reach 50% (low) or 100 % (high) of FII level at final concentration, which correspond respectively in vivo to 13 [9-14] U/kg and 31 [29-34] U/kg in patients. Then, rotational thromboelastometry (EXTEM) and thrombin generation (TG) assay (+/- thrombomodulin) were performed respectively, in whole blood and plasma. Results were compared with healthy controls and expressed as median [interquartile range].

Results: At baseline, patients had a coagulopathy characterized by significant prolonged INR, prolonged EXTEM clotting time and decreased thrombin generation without thrombomodulin. After PCC addition, INR was halved from baseline but did not improve significantly with increasing dose. TG parameters increased supraphysiologically in patients compared to baseline and controls. High-dose of PCC was associated with higher thrombin peak and endogenous thrombin potential (ETP) than low dose (p < 0.05) (Table 1). In addition, PCC increased thrombomodulin resistance, and significant higher resistance was observed with the high-dose (Table 1).

Conclusion(s): Our results support that, compared to high doses, low doses of PCC induce less hypercoagulability in patients with severe liver disease. Clinical studies are required to determine whether low doses of PCC may be used in these patients without increasing thrombotic risk.