1. The concentration in plasma of fibrinogen derivatives fibrinopeptide A (FPA) and Bβ1-42 and the platelet release products β-thromboglobulin (βTG) and platelet factor 4 (PF4) have been determined in patients with acute and chronic liver disease. 2. In 21 patients with fulminant hepatic failure on admission in grade III or IV coma the plasma FPA, Bβ1-42, βTG and PF4 levels were significantly increased compared with those in normal control subjects. On heparinization before haemoperfusion the FPA levels returned to the normal range and during resin and charcoal haemoperfusion there were no significant changes in the coagulation or platelet factors, except for a small increase in FPA with charcoal haemoperfusion. 3. In ten patients with compensated chronic liver disease there was a significant increase in Bβ1-42 and βTG levels but not FPA and PF4 as compared with normal controls. 4. Interpretation of the results is complicated by the possible reduced clearance of these proteins as a result of renal failure in some of the patients with fulminant hepatic failure and also by the damaged liver itself. However, these results have confirmed that disseminated intravascular coagulation can occur in both acute and chronic liver disease.

1. Sera from patients with fulminant hepatic failure (FHF) has previously been shown to contain substance(s) which inhibit leucocyte ouabain-sensitive sodium efflux and rat brain Na + ,K + -dependent ATPase in vitro. Similar effects in the patients could be an important mechanism in the development of encephalopathy and cerebral oedema. 2. In previous studies, bilirubin, free fatty acids and mercaptans have been shown to inhibit Na + ,K + -ATPase in vitro. The present report is concerned with the effects of a number of other potentially toxic substances present in the serum of patients with FHF. 3. Chenodeoxycholic acid, p -hydroxyphenyllactic acid, p -hydroxyphenylpyruvic acid and endotoxin caused 30–45% inhibition of partially purified rat brain Na + ,K + -ATPase at concentrations known to occur in the serum of patients with FHF. At low concentrations the inhibitory effects of these substances were additive, but at higher concentrations a maximum level of inhibition was reached. 4. These further substances are likely, therefore, to be of importance in the disturbances of brain function found in FHF.

1. Serum from patients with fulminant hepatic failure inhibits the ouabain-sensitive sodium efflux in leucocytes. A 1:100 dilution of the serum was necessary before the inhibition became undetectable. 2. Dialysates of the serum through cuprophane in vitro and polyacrylonitrile haemodialysis in vivo were inhibitory in small amounts. 3. Ultrafiltrates (<10 000 daltons) of serum were chromatographed on Sephadex G-25 and the elution profile obtained from patients with fulminant hepatic failure was both qualitatively and quantitatively different from that of normal controls. Material from peaks 3, 4, 5 and 7 in patients with fulminant hepatic failure inhibited leucocyte sodium transport. 4. The dialysate from haemodialysis with the polyacrylonitrile membrane contained most peaks, particularly peaks 4 and 5. Adsorption of serum with polymer coated charcoal in vitro largely removed peaks 5−8.

1. The aim of this study was to define the factors influencing plasma separation from the continuous flow celltrifuge and to evaluate plasma as an alternative to whole blood for perfusion of exchange resins as part of a system of artificial liver support. 2. Studies in vitro showed the importance of packed cell volume, centrifugal force and duration of centrifugation on the degree of plasma separation. From these data it was possible to calculate plasma flow rates likely to be obtained from the celltrifuge when used in vivo. These predicted values correlated closely with plasma flow rates obtained in twenty-six studies in dogs. 3. Comparison of whole blood perfusion with plasma perfusion of exchange resins in another series of dog experiments showed that with whole blood perfusion there was often a considerable rise in pressure across the resin column but that this did not occur with plasma perfusion. 4. Measurements of platelet losses in the same series of experiments showed a 50% reduction of arterial platelet counts over a 3 1/2 h period of perfusion when whole blood was perfused. Although the fall was lower with plasma perfusion, the difference was not statistically significant. 5. Use of the celltrifuge provides a means of resin perfusion free of the mechanical difficulties of whole blood perfusion, but platelet losses still remain a problem.