Evaluation of coagulation abnormalities in acute liver failure.
OBJECTIVE
In acute liver failure (ALF), prothrombin time (PT) and its derivative prothrombin time ratio (PTR) are elevated, and are considered predictors of increased bleeding risk. We aimed at determining whether increased PT/PTR reflects the haemostatic potential and bleeding risk in ALF patients.


METHODS
Twenty consecutive ALF patients were recruited. Samples were analysed on admission for standard laboratory clotting tests (e.g. PT), thromboelastography (TEG), individual pro and anticoagulant factors and thrombin generation (TG) kinetics with and without Protac, a snake venom protein C activator, and microparticle assay. TG was also measured in 20 age and sex matched healthy volunteers.


RESULTS
PT was significantly raised (50.7s ± 7.2, p=0.0001) but did not correlate with TEG parameters. TEG tracings were consistent with a hypocoagulable state in 20%, normal in 45%, and hypercoagulable in 35% of the patients. There was a concomitant and proportional reduction in plasma levels of both procoagulants and natural anticoagulant proteins, in conjunction with a significant elevation in plasma levels of factors-VIII (FVIII) and Von Willebrand factor, and microparticles, culminating in an overall efficient, albeit reduced, thrombin generation capacity in comparison with healthy individuals. A heparin-like effect (HLE) was also noted in most patients. No significant clinical bleeding complications occurred and no blood transfusions were required.


CONCLUSIONS
In ALF, despite grossly deranged PT in all patients, estimation of bleeding risk suggests that the coagulation disturbance in ALF patients is complex and heterogeneous for which an individualised approach is required.
Department of Intensive Care Medicine, Royal Free Hospital, London, United Kingdom.
Banwari
B
Agarwal
Gavin
G
Wright
Alex
A
Gatt
Anne
A
Riddell
Vishwaraj
V
Vemala
Susan
S
Mallett
Pratima
P
Chowdary
Andrew
A
Davenport
Rajiv
R
Jalan
Andrew
A
Burroughs
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055252:Cell-Derived Microparticles; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006487:Hemostasis; D006496:Heparinoids / Q000097:blood; D006801:Humans; D019934:International Normalized Ratio; D017114:Liver Failure, Acute / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011517:Prothrombin Time; D012307:Risk Factors; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000378:metabolism
D006496:Heparinoids; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII; D005340:Fibrinogen; D013917:Thrombin