ANTICOAGULANTS IN CORONARY THROMBOSIS

536

of approach .may be said to be so, for the investigatorsaim at following processes step by step, any falteringbeing signalled to the observer by the Geiger countersin circuit.

ANTICOAGULANTS IN CORONARY THROMBOSISEMBOLl and tnromboses in various parts of the a,rterial

system are recognised complications of coronary throm-bosis, occurring in 14% of Blumer’s 1000 cases,1 and in18 of the 100 cases reported by Nay and Barnes.2 Thesecomplications have usually been attributed to narrowingof the arterial lumen and stasis in the blood-flow, butPeters and colleagues 3 have noted that in three-quartersof their patients with coronary thrombosis there wasan increased prothrombin activity. This observation isin agreement with de Takats’s 4 observation that patientswith coronary thrombosis show an increased resistanceto hepa,rin.

In view of Solandt and Best’s evidence 5 that myo-cardial infarction and thrombus formation in the

coronary tree can be prevented by the administration ofheparin, it was only natural that physicians shouldconsider its clinical application. There are difficultiesand even dangers in this use of heparin ; but the intro-duction of dicoumarol by Link and his colleagues 6gave fresh impetus to the study, and several reportshave recently appeared in American journals. ’ Petersand his associates have used dicoumarol in a series of50 patients with coronary thrombosis, among whom theincidence of clinical embolism was 2%, as against 16%in a control group. The mortality-rate in the dicoumarolgroup was 4%, compared with 20% in the untreatedgroup. Although dicoumarol was given for at least sixweeks and sometimes much longer, no serious toxiceffects and no frank haemorrhages were noted ; but inthree patients microscopic haematuria was found. Itis emphasised that this treatment should be given onlywhen there is a laboratory for the estimation of theprothrombin clotting-time. Definite contra-indicationsare hepatic disease and any blood dyscrasia. Specialcare must be exercised in the presence of hypertension,and the dicoumarol-like action of salicylates 8 andquinine 9 must be borne in mind. Dosage was determinedentirely by the prothrombin clotting-time of dilutedplasma (12-5%), for which the normal is 85-100 seconds.The usual dose is 300 mg., which can be repeated dailyunless the prothrombin clotting-time of 12.5% plasmareaches 400 seconds, which is the upper limit of safety.Haemorrhage, should it occur, can be controlled by theintravenous administration of menadione bisulphite37-5 mg. The scheme is very similar to that of Wright,7who uses the prothrombin time of undiluted plasma ashis guide : the normal figure here is 13-17 seconds, anddicoumarol was discontinued if the time exceeded 30seconds. Wright’s report is only a preliminary one ;

but, considering that most of his patients were selectedfor treatment because of repeated episodes of multiplethrombi or repeated embolic phenomena elsewhere inthe arterial tree, his results are certainly encouraging.Of 43 patients selected because of complications knownto be associated with a very high mortality-rate, only11 (25%) died, compared with an anticipated risk of

60-70% ; while of 33 patients having their first or seconduncomplicated attack of coronary thrombosis, 4 (12%)died, compared with an anticipated mortality of 20-30%.Two further aspects are worth considering. It has

been confirmed by Peters and his co-workers that one1. Blumer, G. Ann. intern. med. 1937, 11, 499.2. Nay, R. M., Barnes, A. R. Amer. Heart J. 1945, 30, 65.3. Peters, H. R., Guyther, J. R., Brambel, C. E. J. Amer. med. Ass.

1946, 130, 398.4. de Takats, G. Surg. Gynec. Obstet. 1943, 77, 31.5. Solandt, D. U., Best, C. H. Lancet, 1938, ii, 130.6. Campbell, H. A., Smith, W. K., Roberts, W. L., Link, K. P.

J. biol. Chem. 1941, 138, 1.7. Wright, I. S. Amer. Heart J. 1946, 32, 20.8. Shapiro, S. J. Amer. med. Ass. 1944, 125, 546.9. Pirk, L. A., Engelberg, R. Ibid, 1945, 128, 1093.

risk in using digitalis for the heart-failure of coronarythrombosis is its tendency to increase the clotting-timeof the blood.10 Does dicoumarol neutralise this danger IScherf and Schlachman 11 found that the prothrombintime and the plasma coagulation time are shortenedafter the intravenous administration of theophyllinewith ethylenediamine, and also of theophylline sodiumacetate. A similar effect was obtained by the oraladministration of the methylxanthines (theophyllinewith ethylene diamine, theobromine, and theobronlinesodium aceta.te). This is not a new observation (someof the earlier German workers actually recommendedtheophylline with ethylenediamine as a coagulant, andWright gave it as part of his " conventional treatment "*to patients receiving dicoumarol) ; but it suggests thata careful review of our treatment of coronary thrombosisis called for. Until much fuller data are obtaineddicoumarol should clearly be used only in selectedcases treated in hospitals.

SIXTH AND LAST

THE final issue of the sixth volume of the Bulletin ofWar 3tedicine contains two epilogues which mark theend of this publication. The first, by Sir EdwardMellanby, F.R.S., secretary of the Medical ResearchCouncil, recounts briefly the history of its inception ; thesecond, by Dr. Charles Wilcocks, director of the Bureauof Hygiene and Tropical Diseases, acknowledges theservices of all those whose work contributed to the valueof the Bulletin. Together, these epilogues reflect a fruitfulcollaboration between the Medical Research Council andits publications officer, the bureau, and the large numberof abstracters who devoted part of their meagre leisureto the task of providing medical information for thosewho otherwise might have missed it. Though theimmediate purpose of the Bulletin has now been served,the medical historians of the war will find in it muchof the material they may need for describing the develop-ments of that period of-in some directions-phenomenalprogress. The rapid growth of knowledge in relation totransfusion, penicillin, D.D.T., and mepacrine, for instance,is reflected in these abstracts.The enormous importance of diseases (especially

tropical diseases) in military campaigns has beenreaffirmed during the war, when the success of operationsturned on the maintenance of forces healthy enough toundertake them. That many of the problems involvedwere quickly solved was largely due to the stimulus

given to research by the urgency of the situation. Butthe same or similar problems persist among the indigenousinhabitants of these tropical countries, and we musthope that research will be pursued as vigorously forpeace as for war. There is still, therefore, the same needfor information on tropical diseases and on public-healthmeasures, and this will continue to be supplied by thebureau in its two publications, the Tropical DiseasesBulletin and the Bulletin of Hygiene, which were inexistence long before the war, and which were the modelson which the Bulletin of War lTedicine was based.

A MEETING has been arranged at the London School ofHygiene, Keppel Street, London, W.C.I, for Thursday,Oct. 17, at 3.30 P.M., with the object of inaugurating a.council for the care of spastic children. The chair will betaken by Mr. G. R. Girdlestone, F.R.c.s. The actingsecretary is Mr. H. P. Weston, c/o Council for the Care ofCripples, 34, Eccleston Square, S.W.I.

WE regret to record that Lieut.-Colonel R. J. C.THOMpsol.7, who retired from the secretaryship ofSt. Thomas’s Hospital medical school last month, died onOct.. 2. He was 66 years of age.

10. de Takats, D., Trump, R. A., Gilbert, N. C. Ibid, 1914, 125,840.

11. Scherf, D., Schlachman, M. Amer. J. med. Sci. 1946, 212,83.