OC-069 Rotational thromboelastometry in cirrhosis: hypercoagulable and hyperfibrinolytic

Abstract

BACKGROUND Cirrhotic patients have complex acquired derangements of haemostasis. Routine coagulation tests suggest a hypocoaguable profile, resulting in frequent administration of blood components for prophylaxis and treatment of bleeding. Rotational thromboelastography (ROTEM®), unlike standard coagulation tests, provides a real-time measurement of clot formation, strength and stability in whole blood and may more accurately reflect In Vivo coagulation. AIMS 1) To identify the key derangements in the haemostatic pathways in patients with cirrhosis; 2) To determine the prevalence of overt hyperfibrinolysis in patients with cirrhosis and whether this could be improved by anti-fibrinolytics. METHODS: We used ROTEM® to investigate: 1) Clotting time (CT) and maximum clot firmness (MCF) in stable, non-bleeding cirrhotics compared to healthy volunteers; 2) The correlation between ROTEM® parameters of coagulation and routine coagulation tests; 3) The presence of overt hyperfibrinolysis and whether this could be reversed by spiking blood samples ex-vivo with the antifibrinolytic aprotinin (APTEM test). Overt hyperfibrinolysis was defined by a maximum lysis (ML) of >15% and by comparing the clot lysis index at 60 mins (CLI60) between EXTEM and APTEM parameters. RESULTS: 106 adult cirrhotics and 28 healthy volunteers were enrolled after informed consent. Median EXTEM CT was shorter in cirrhotics than controls (51s vs. 58s, p<0.01) and the CT clotting time shortened as Child-Pugh score increased in severity (52s Child A, 49s, Child B, 47s Child C). In cirrhotics there was strong correlation between EXTEM MCF, and both platelet count (r=0.801, p<0.0001) and fibrinogen levels (r=0.653, p<0.0001), as well as fibrinogen and FIBTEM MCF (r= 0.641, p<0.0001). 25% (26/106) of cirrhotics had evidence of overt hyperfibrinolysis. No healthy volunteers had evidence of hyperfibrinolysis. After spiking samples from cirrhotics with aprotinin, hyperfibrinolysis was completely reversed (ML<15%) in 13/26 cases and partially reversed in 13/14 cases. There was a significant reduction in the median ML between EXTEM and APTEM clot profiles (13 vs. 11, p<0.001) and an increase in the median LI60 (91% vs. 93%, p<0.001) from EXTEM to APTEM test. D-dimer levels increased with increasing disease severity (Child A- 894, Child B- 1835, Child C-5281). CONCLUSIONS: ROTEM® demonstrated hypercoagulable clotting time in cirrhotics, despite prolonged PT, APTT thrombocytopenia and hyperfibrinolysis supporting the concept of re-balanced haemostasis. Use of ROTEM® may avoid unnecessary and potentially harmful transfusion of pro-coagulant blood components in cirrhotics. The high prevalence of overt hyperfibrinolysis in cirrhosis requires further elucidation and clinical studies to investigate the role of anti-fibrinolytics in the prophylaxis of variceal bleeding.