Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 ± 0.03 U/ml S.E.; at 1 hr 0.99 ± 0.06 U/ml; p <0.001; control prelevels: 0.24 ± 0.03 U/ml; at 1 hr 0.23 ± 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,005 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p <0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III—supplemented subjects (0.40 ± 0.07 U/ml compared with 0.22 ± 0.05 U/ml in the control group; p < 0.05). The significant reduction in platelet count observed in the control patients (18% ± 6% at 1 hr; p < 0.05) did not occur in antithrombin III patients (6% ± 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein β-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis. Over the course of the study, no significant difference was seen in the frequency of bleeding from vascular access sites, gastrointestinal tract or other locations.
Thus in a controlled study, supplementation of antithrombin III markedly reduced the amount of heparin required during hemodialysis of patients with fulminant hepatic failure and also reduced platelet losses. Antithrombin III supplementation may be of benefit in hemodialysis, continuous arteriovenous hemofiltration or other invasive techniques requiring anticoagulation in these patients at particular risk of bleeding. (HEPATOLOGY 1991;14:251–256.)