Platelet function in chronic liver disease: relationship to disease severity.

Abnormalities of platelet aggregation in response to adenosine diphosphate in 56 patients with chronic liver disease correlated with impairment of hepatocellular function but not with the etiology of the liver disease. Platelet-poor plasma from some patients appeared to contain an inhibitor since, in cross-over studies, it reduced the degree of aggregation of control subjects. However, platelet-poor plasma from some other patients enhanced aggregation in controls, and this was thought to be due to the presence of fibrin monomer. In the majority of patients with severe liver disease, platelet function still appeared defective, even after exclusion of the effects of plasma, and was independent of the platelet count in peripheral venous blood. Since patient platelet volumes were smaller than those of controls, these findings might be explained by deficiency of the larger hemostatically active type of platelet as a consequence of either bone marrow failure or splenic sequestration.

Platelet function in fulminant hepatic failure and effect of charcoal haemoperfusion.

In 34 patients with fulminant hepatic failure, platelets, in addition to being reduced in numbers, were smaller than those of healthy controls. In keeping with this, capillary bleeding times were significantly longer than could be accounted for by reduction in numbers alone. In a small group of these patients use of charcoal haemoperfusion for temporary liver support produced a doubling of the capillary bleeding time despite only a small drop in arterial platelet counts. This disproportionate prolongation of bleeding time was almost certainly caused by the loss of larger platelets in the charcoal columns during perfusion, as the mean median volume also fell during perfusion. Rises in screen filtration pressure of blood leaving the columns were found during some perfusions and thought to be indicative of platelet aggregates. Release of vasoactive substances from platelets could account for the hypotension often found at this time.

Biocompatibility of coated and uncoated charcoal during haemoperfusion in healthy dogs.

The biocompatibility of two commercially available charcoal columns, one containing coated and the other uncoated but immobilized charcoal, was compared during four haemoperfusions with each in eight healthy greyhounds. Reductions in arterial levels of platelets (49% and 42% respectively) and leucocytes (both 21%) were similar. Microaggregates, detected by the Swank screen filtration pressure technique, were found in blood leaving the columns during three of the four perfusions with each column. Another twelve perfusions with the uncoated column were carried out with the addition of one or other of the following three agents which inhibit platelet aggregation: sulfinpyrazone, dipyridamole, or citrate-phosphate-dextrose. With none of these were platelet losses less as compared with the four perfusions in which heparin only was used. However, rises in screen filtration pressure were less pronounced. In other perfusions, where its dosage was varied, heparin was shown to reverse, and in large doses delay, the appearance of micro-aggregates. Thrombus in the column itself may be a source of microaggregates, but platelet aggregation in the absence of thrombus deposition may be responsible. The relation of these findings to micro-aggregate formation, which has constituted a clinical problem during charcoal haemoperfusion in humans with fulminant hepatic failure, is considered.