Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography

Abstract

Background & aims: Patients with acute liver injury/failure (ALI/ALF) are assumed to have a bleeding diathesis on the basis of elevated INR; however, clinically significant bleeding is rare. We hypothesized that patients with ALI/ALF have normal hemostasis despite elevated INR.

Methods: Fifty-one patients with ALI/ALF were studied prospectively using thromboelastography (TEG), which measures the dynamics and physical properties of clot formation in whole blood. ALI was defined as an INR ≥1.5 in a patient with no previous liver disease, and ALF as ALI with hepatic encephalopathy.

Results: Thirty-seven of 51 patients (73%) had ALF and 22 patients (43%) underwent liver transplantation or died. Despite a mean INR of 3.4±1.7 (range 1.5-9.6), mean TEG parameters were normal, and 5 individual TEG parameters were normal in 32 (63%). Low maximum amplitude, the measure of ultimate clot strength, was confined to patients with platelet counts <126×10(9)/L. Maximum amplitude was higher in patients with ALF than ALI and correlated directly with venous ammonia concentrations and with increasing severity of liver injury assessed by elements of the systemic inflammatory response syndrome. All patients had markedly decreased procoagulant factor V and VII levels, which were proportional to decreases in anticoagulant proteins and inversely proportional to elevated factor VIII levels.

Conclusions: Despite elevated INR, most patients with ALI/ALF maintain normal hemostasis by TEG, the mechanisms of which include an increase in clot strength with increasing severity of liver injury, increased factor VIII levels, and a commensurate decline in pro- and anticoagulant proteins.

Figure 1. Representative thromboelastogram from a patient with acute liver failure from acetaminophen

The tracing is normal in all of the 5 TEG parameters indicated despite an INR of 4.2: (R-time, 3.8 min; K-time, 1.1 min; α-angle, 73.8 degrees; MA, 63.0 mm; lysis at 30 min, 0.3%). At the time of this TEG, the patient had grade 3 hepatic encephalopathy and venous ammonia of 120 μmol/L. Other coagulation components included: platelet count, 163 × 10⁹/L; fibrinogen, 189 mg/dl; factor VII, 4% of normal; factor VIII, 558% of normal; protein C, 5% of normal.

Figure 2. Maximum amplitude of clot formation according to the number of SIRS concurrently determined in patients with acute liver injury/failure on admission to study

Data represent mean values with lower/higher 95%; width of columns reflect number of patients with indicated number of SIRS. (P = 0.024 for trend).