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SUMMARY 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.

SYNOPSISThe effect of heparin therapy was followed in 50 patients treated for thrombo-embolic disease. Individual response to a standard dose of 40,000 units of heparin daily showed a considerable variation and the effect was not constant on subsequent days. Five of the 50 patients developed a serious haemorrhage.It is proposed that to ensure the adequacy of treatment detectable levels of heparin should be obtained but because of the high risk of bleeding these levels should not be excessive.The results suggest that control of heparin therapy can be based on the thrombin clotting time. Using this test it is advised that treatment is monitored daily in order to achieve a plasma heparin level of up to 1 mg per 100 ml. Classical laboratory control is with the whole blood clotting time. It is often said that this should be prolonged to between one and a half and three and a half times the normal value for the individual. On intermittent intravenous injection the test should be taken just before the next dose is due. It is not clear whether the same criteria should be used for continuous heparin infusion. The clotting time is imprecise, difficult to standardize, and if any degree of accuracy is to be obtained the test must be performed at the bedside and at 37°C. Few will be content to wait the long time till the endpoint is reached. Since heparin inhibits the action of thrombin many of the standard clotting tests should be affected. Some of these were first examined for their sensitivity to the effect of heparin added to normal plasma. Blood from a series of 50 patients who were receiving heparin infusions was then examined to test these laboratory findings in practice.

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