Pharmacological Reviews, Vol 13, 279-328, Copyright © 1961 by the American Society for Pharmacology and Experimental Therapeutics

ANTICOAGULANT THERAPY

¹ Louis Jenner Laboratory, St. Thomas's Hospital and Medical School, London, England

Anticoagulant drugs have been considered in their clinical rather than their experimental context, for it is the problems of the assessment of therapeutic effect and of the control of dosage which are now being most keenly discussed. Space has been devoted to the evidence for therapeutic benefit in different thrombotic conditions, and to the practical difficulties which may be encountered. The control of dosage has been discussed in some detail, and an integration of the clinical and laboratory problems has been attempted. These, of course, are concerns which have attracted the attention of many able people, to only a fraction of whose work has it been possible to refer.

Good evidence has been found to support the value of anticoagulant.s in venous thrombosis, but their effect on arterial thrombosis is less marked. Routine administration to patients with fractured femur led to a marked reduction in the incidence of venous thrombosis and of embolism; a similar result was obtained after obstetric and gynaecologic surgery. The treatment of established venous thrombosis did not eliminate pulmonary embolism, but did reduce the morbidity of the primary thrombosis. Nevertheless, even after pulmonary embolus had been diagnosed, anticoagulant treatment reduced the immediate mortality and the danger of recurrence. In the chronic stage of rheumatic heart disease the incidence of thromboembolic episodes was much reduced. In coronary artery disease and myocardial infarction definitive studies have proved difficult to set up, owing to the number of factors which influence prognosis and which therefore have to be controlled; the evidence is incomplete but suggests that some benefit may be expected. In the acute phase, at least a reduction in secondary thrombosis seems established ; and long-term treatment may somewhat reduce the mortality. In peripheral arterial disease the effect on the arterial lesions is dubious.

Overdose bleeding may be reduced by withholding anticoagulants from patients with local lesions liable to bleed. Minor haematuria or provoked purpura ("capillary fragility" tests) are of little value as warning signs of major bleeding. Surprisingly, the coumarin-indanedione drugs do not greatly impair surgical haemostasis. Side-effects other than bleeding seem to be rare with either coumarins or indanediones, but perhaps a little more frequent with the latter.

The development of Quick's test and of Owren's "P & P" and "Thrombotest" is described and their relative merits are discussed. The Quick test is still being found satisfactory in many hospitals but the Thrombotest would seem to have definite advantages under certain circumstances.

The reviewer has thus aligned himself soberly with the enthusiasts for anticoagulant treatment; but he remains conservative in continuing to use Quick's one-stage prothrombin time test for control.

Note:

I should like to thank Professor P. Owren and Messrs. Nyegaard and Co., A/S, Oslo, Norway, for permission to reproduce Figures 1 to 3 ; Dr. C. F. Borchgrevink, for putting his results at my disposal in advance of publication (ref. 31) ; Dr. G. A. Carnachan of Evans Medical Ltd., Liverpool, England, for certain references; and C. W. Peck, Esq., F.P.S., Pharmacist to St. Thomas's Hospdital, London, England, for his advice on the names of drugs. I am very grateful to Miss D. Burridge for the typescript.