P. T. Flute

LOW DOSES OF HEPARIN IN PREVENTION OF DEEP-VEIN THROMBOSIS

Abstract The effectiveness of subcutaneous heparin in the prophylaxis of deep-vein thrombosis was investigated in 53 consecutive patients over the age of 50 undergoing repair of inguinal hernia. Deep-vein thrombosis was detected by means of the 125 I-fibrinogen test in 7 (26%) of the 27 control patients, while this was significantly reduced (4%) in the 26 similar patients who received heparin before and after surgery.

EARLY AND INTENSIVE THERAPY OF INTRAVASCULAR COAGULATION IN ACUTE LIVER FAILURE

Four consecutive patients, three with fulminant hepatic failure and one with a severe relapse of serum hepatitis, who showed evidence of intravascular coagulation, were treated intensively with heparin and fresh frozen plasma. Rapid correction of the coagulation disturbance was achieved, and all four patients recovered completely. The necessity for starting such treatment early in the course of the disease and before the onset of major gastrointestinal bleeding is stressed, and it is suggested that intravascular coagulation may act as an intermediary in the pathogenesis of the hepatic necrosis.

Liver Transplantation in Man—II, a Report of two Orthotopic Liver Transplants in Adult Recipients

Two patients with primary hepatic malignancy were treated by hepatectomy and orthotopic liver transplantation. In both cases the donor liver was infused with cold solutions and kept chilled without continuous perfusion. There was immediate satisfactory hepatic function in both transplants. The first patient died after 11 weeks from overwhelming bacterial and fungal infections probably secondary to hepatic infarction due to thrombosis of the recipient hepatic artery. The thrombus occurred at the site of the arterial clamp. In an attempt to control the growth before transplantation, the patient had been treated with large doses of chlorambucil, which resulted in extreme marrow depression and septicaemia. The second patient developed cholestatic jaundice during the second and third weeks after transplantation, with histological evidence of mild rejection, which was controlled by increasing the dose of immunosuppressive agents. He is now well, having returned to work six weeks after the operation. Though the first patient showed no evidence of rejection, it is concluded that patients receiving liver allografts should receive immunosuppressive therapy.

Liver Transplantation in Man—IV, Haemorrhage and Thrombosis

Blood coagulation and fibrinolytic factors have been measured in 13 patients treated by liver transplantation. During operation intravascular coagulation and fibrinolysis were increased, but seldom to a degree which would cause abnormal bleeding. Measurement of the catabolism of radioactive fibrinogen showed that increased intravascular coagulation continued for long periods after the operation. Despite secondarily increased fibrinolysis, there was a high incidence of thrombosis. Treatment with anticoagulants or with fibrinolysis inhibitors may be valuable in these patients.

FIBRINOLYTIC ACTIVITY AND POSTOPERATIVE DEEP-VEIN THROMBOSIS

Abstract 95 patients undergoing gynaecological operations were studied in a double-blind trial to assess the effect of phenformin and ethylœstrenol, given for four weeks, on the incidence of post-operative deep-vein thrombosis (D.V.T.). 45 patients received phenformin and ethylœstrenol and 50 patients received placebo preparations. Although phenformin and ethylœstrenol produced a significant shortening of the dilute blood-clot lysis-time, there was no difference in the incidence of D.V.T. in the two groups of patients.

Liver Transplantation in Man—III, Studies of Liver Function, Histology, and Immunosuppressive Therapy

The experience gained from 13 hepatic transplant operations is described, with particular reference to the findings in nine patients who survived the immediate operative period. A major problem was found to be infection. Fulminant pneumonia caused death in two adults, at a time when liver function was virtually normal. Infection related to bile fistula and sepsis may be overcome by an improved method of biliary drainage by cholecyst-dochostomy, which was carried out in the last two patients. Jaundice in the second week due to rejection was observed in several patients. The striking histological change was centrilobular cholestasis. The jaundice, which was not prevented by administration of antilymphocyte globulin, was rapidly controlled by temporarily increasing die dose of prednisone. One patient who survived for four and a half months and who had a poor tissue match subsequently developed chronic rejection with progressive cholestatic jaundice. Five of the patients were able to go home and at time of publication two are alive and well 14 and 20 weeks after treatment.

Experimental hepatic necrosis: Studies on coagulation abnormalities, plasma clearance, and organ distribution of 125I-labelled fibrinogen

Studies in the rat with hepatic necrosis induced by carbon tetrachloride showed that the abnormalities in one-stage coagulation tests and the increased catabolism of fibrinogen were similar to those found in man with acute viral or drug-induced hepatic necrosis. Determination of the distribution of the radioactive label shows that excessive deposition was maximal in the liver but also occurred in the spleen. The appearance is delayed by heparin but accelerated by tranexamic acid.

Fibrinogen metabolism in acute hepatitis and active chronic hepatitis.

Summary. Coagulation studies, including those of radioactive fibrinogen metabolism, were performed in seven patients with acute viral hepatitis and 12 patients with active chronic hepatitis. An increased fractional catabolic rate for fibrinogen was observed in four patients from the first group, and seven from the second. The catabolic rate was increased in those patients with the greatest degree of hepatic necrosis as demonstrated by the raised serum aminotransferase levels. There was no correlation between the rate of fibrinogen catabolism and the standard clotting tests, but the SDPS test (indicating the presence of fibrin monomers in the circulation) was consistently positive in those cases where the catabolic rate was increased.

Factor VIII levels during the course of acute hepatitis in a haemophiliac.

A 51-year-old patient with haemophilia since childhood (usual factor VIII level 14%) developed acute viral hepatitis type B two months after an operation which had been covered by cryoprecipitate. The course of the hepatitis following admission was severe with encephalopathy and ascites. Evidence of intravascular coagulation with an increased radioactive fibrinogen turnover was also present. The factor VIII level measured by a one-stage clotting factor assay rose rapidly to 200% of normal and remained at this level for two weeks, and factor-VIII-related antigen as measured by electroimmunoassay also became greatly elevated (900% of normal). The possible mechanisms underlying those surprising changes are discussed.