ACUTE PORPHYRIA

193

Letters

to

the Editor

CORONARY DISEASE

Professor Ryle’s contention (Nov. 9) that mental and emotional strain are potent factors in causing coronary thrombosis in professional men, so sceptically received by Sir Henry Bashford (Nov. 23), gets a certain gloomy support from the obituary columns of the Journal of the American Medical Association (September-

November, 1944).

,

I find that in 1000 consecutive notices where the cause was given--and very rarely was it not-22 % of the deaths were ascribed to coronary thrombosis. The really interesting observation, however, was that of a select 7% whose worldly fame merited an obituary of over fifteen lines no less than 41 % died of coronary diseasedouble the number among their less conspicuous

colleagues.

The above figures show that the greater incidence of coronary disease among the " famous ". men cannot be accounted for by their being older than the less famous. There seems, then, to be a definite relation between " greatness " in the profession and susceptibility to coronary disease. Moreover the relation does not apply to other forms of cardiovascular diseases, for the difference observed on the samples taken is not significant. The " greater " the man the poorer the arteries seems to be the rule ; but whether this is due to a greater burden of work and responsibility is coniecture only. DONOUGH O’BRIEN. London, S.W.3. FATAL USE OF A DANGEROUS UNIVERSAL DONOR SIR,—Maior Sevitt (Dec. 28) has rightly observed that there is slender evidence for the conclusion by Dr. Morgan and Dr. Lumb (Dec. 14) that their patient died as the result of a transfusion of blood containing high-titre incompatible anti-A agglutinins. This conclusion can be established with certainty only when it has been demonstrated that the patient’s own cells have been haemolysed, and that the cells of the transfused blood are showing a normal survival-time in the recipient’s circulation. Morgan and Lumb’s paper is of value, however, in reminding us of one of the dangers associated with the routine transfusion of group-0 blood. They recommend that group-0 blood should be accepted as "universal, donor blood " only if the titre of the anti-A and anti-B agglutinins in the plasma is below 256. This is a wise precaution, but their paper would have still further assisted in combating the hazards of blood-transfusion had it contained a warning that the phrase " universal donor blood " is a grave misnomer which should be deleted from medical

terminology. The term " universal donor " was introduced when it thought there were only two corpuscular agglutinogens-those we now call A and B. When neither of these could be demonstrated in certain red-blood corpuscles it was concluded that blood of this type was free from all potentially dangerous reactors. This conclusion has been proved false. Corpuscles lacking A and B contain an agglutinogen 0 ; 80 % contain a factor M and a similar number a factor P. The plasma of some potential recipients contains natural antibodies incompatible with one or more of these agglutinogens. Group-0 blood will be accepted as "-universal donor blood" by none of these recipients. In addition, all corpuscles of group 0 contain a minimum of three Rh and/or rh factors. Women who have had stillborn or jaundiced babies, and patients who have had previous blood-transfusions, may have formed immune antibodies to one or more of these factors, and may react fatally if transfused with " universal donor " corpuscles containing the corresponding antigen. 85 % of corpuscles of group 0 contain an Rh agglutinogen D. Levine has was

demonstrated that the indiscriminate transfusion of females with corpuscles containing this antigen may result in the recipient giving birth to a stillborn baby at a subsequent pregnancy. Our so-called " universal donor " corpuscles are still further complicated by antigens described as Kell, Lutheran, and Lewis. It is very evident, therefore, that there can be no such thing as " universal donor blood." The term should be assiduously avoided and the fact faced that, before transfusion, all blood to be given must be tested for direct compatibility against the potential recipient’s serum or plasma. The only exception to this rule should be the case where urgency is too extreme to permit of such a test. At a first transfusion incompatible reactions from natural antibodies in the plasma of the recipient can be excluded by the simple type of slide-compatibility test well known to all pathologists-a test which all practitioners giving transfusions should be prepared to undertake. More elaborate tests are required when the patient has received a previous transfusion, and especial caution is necessary when these transfusions have been accompanied by reactions, or the recipient is a woman who has given birth to a child affected with haemolytic disease. All such cases should be referred to a bloodgroup laboratory whenever practicable. The serious consequences resulting from sensitisation to the D antigen will be prevented only when it becomes possible never to give D-negative females blood containing the D antigen. " " Group-to-group transfusion will prevent the type of reaction described by Morgan and Lumb. There is an even more urgent reason, however, for the immediate adoption of this practice. The giving of group-0 blood to patients other than group 0 is placing a great and unnecessary strain upon’the group-0 blood-donor panels. It behoves all clinicians therefore not only to test for compatibility before transfusion but to make every effort to ensure that recipients are given blood of homologous group. More blood will then be available, and there will not be the same risk that the group-0 donor may suffer such a surfeit of bleeding that his appetite for blood donation mav " sicken and so die." GEOFFREY H. TOVEY South-West Regional Transfusion Regional Transfusion Officer. Centre, Southmead, Bristol.

ACUTE PORPHYRIA

SIR,—The article by Jorgensen and With in your issue of Jan. 11 serves a valuable purpose in drawing attention to the syndrome of acute porphyria, but we feel that a number of statements may prove misleading. In reference to lead poisoning, the authors state that the condition encountered is a porphyria and that the only porphyrin excreted is coproporphyrin I. According to Waldenstrom’s1 classification, to which the authors refer, the term porphyria is reserved for two familial diseases of unknown aetiology ; increased excretion of coproporphyrin following poisoning by lead, &c., is regarded as symptomatic and is referred to as porphyrinuria. Whereas the porphyrin of normal urine2 and that of patients with haemolytic anæmia3 is predominantly coproporphyrin i, that excreted in large amounts in lead poisoning has definitely been identified as coproporphyrin jll,4 a fact which may be of value in the diagnosis of the condition. Secondly, whereas Jorgensen and With do not make any reference to the simple and effective test for porphobilinogen devised by Watson and Schwartz,5 we would point out that whenever routine examination of a urine reveals a positive Ehrlich aldehyde reaction but a negative Schlesinger test, the presence of porphobilinogen should be suspected, since this material, unlike urobilinogen, does not give a green fluorescence when alcoholic zinc acetate is added to urine containing it. Watson and Schwartz’s modification of the aldehyde reaction may then be applied for confirmation. Waldenström, J. Acta. med. scand. 1937, suppl. 82. Grotepass, W. Z. physiol. Chem. 1938, 253, 276. Dobriner, K. J. biol. Chem. 1936, 113, 1. Grotepass, W. Z. physiol. Chem. 1932, 205, 193. Vigliani, E. C., Waldenstrom, J. Dtsch. Arch. klin. Med. 1937, 180, 182. 5. Watson, C. J., Schwartz, S. Proc. Soc. exp. Biol., N.Y. 1941, 47, 393. 1. 2. 3. 4.

194 We consider it dangerous to advise that if, in a case of acute porphyria, porphobilinogen be absent from the specimen examined, any examination for increased amount of porphyrin may be dispensed with. The conversion of porphobilinogen to porphyrin and porphobilin takes place with some speed in these acid urines and might have occurred to completion before the specimen was examined. Direct spectroscopic examination of a suspected urine before and after the addition of a few drops of concentrated hydrochloric acid is extremely easy to perform and in our hands has proved very informative and reliable. Confusion of the absorption spectra of porphyrin metal complexes, frequently seen in these urines, with the bands of oxyhamoglobin is readily avoided if the shift in position on addition of the acid is watched for. There is no justification for describing the test, performed in this way, as useless or

suspected

,

misleading. Should a quantitative determination of uroporphyrin be desired, a technique based on adsorption behaviour is available.s We feel that too little attention is paid by Jorgensen and With in their article to the work of Watson and his collaborators 78 on the nature of the uroporphyrin III fraction, in which the porphyrin hitherto accepted as uroporphyrin ill is alleged to be in reality a mixture of at least two porphyrins. It is clear that further work is necessary before one can dogmatise on the significance of structural differences in the realm of porphyrin metabolism. We would also like to draw attention to the fact that the structure for porphobilinogen proposed by Waldenstrom 9 and quoted by Jorgensen and With is unsatisfactory in that consideration is not given to the necessary introduction of two carbon atoms (as methine bridges) when porphobilinogen is transformed into uroporphyrin, or of one such carbon atom during the formation of porphobilin. C. H. GRAY C. RIMINGTON. London. THE CRUX

SIR,—Your leader of Jan. 25 makes good reading; but of the matter is implicit not so much in that article, or in the admirable letter by Mr. H. Taylor, as in the other letter, entitled Rescue of General Practice, by Mr. Wilfrid Adams. Though, in order to uncover its final meaning, one has to ask the question as to why this rescue is necessary. The answer then comes out-because the new Act plans to abolish the private patient who is in fact the crux. The private patient is the crux because he provides the fee. Now I know it is fashionable to deprecate money, especially money freely earned. The very young often despise it; those who lack it hate it; and the B.B.C. discussion groups, together with those who talk unctuously of " the community," try to cry it down. Yet in reality the private fee is an inestimable boon ; for it gives more than anything else to the general practitioner his chance to excel: to become proficient in minor surgery; in modern therapeutics, psychology, and here I can see the medical anaesthetics, X rays, &c. ; purist raising his eyes in horror at the thought of these crafts being handled by anyone but the appropriate specialist. I am aware also that the quack, whether medically qualified or not, may at times cash in on the fee system ; which is a pity, but we live in an imperfect world. I long to discover, but so far without success, how the

surely

the

crux

100 % capitation system or the whole-time salary can operate in general practice with anything approaching the efficiency of the private fee as a stimulant to good work on the part of the doctor. I am therefore compelled to visualise the new health service as a great leveller (which one must admit is what some socialists seem to want). One in which the slacker or the nincompoop will find himself on equal financial terms with the born doctor ; and wherein the needs of the patient will be met by a closely knit trinity-the district nurse, the 6. Rimington, C. Biochem. J. 1943, 37, 443. 7. Grinstein, M., Schwartz, S., Watson, C. J.

157, 323.

J. biol. Chem. 1945,

8. Watson, C. J., Schwartz, S., Hawkinson, V. Ibid, 1945, 157, 323, 345. Vahlquist, B. Z. physiol. Chem. 1939, 260, 189.

9. Waldenström, J.,

relieving officer,

and

the

domiciliary

health worker

(alias G.P.). And I draw the inevitable conclusion that the way for a vigorous medico to escape from this embrace is by getting himself " upgraded " into the ranks of the petty specialists. And what of the residuum, the "backbone" of our profession, to whom the high-ups still pay lip service ? Time runs short. The new Act (axe I nearly wrote by mistake) will soon be upon us. We must speak out our fears. We must make them known not only to authority but also to the students who so far don’t know. For if these problems are neglected, the new service, however imposing its machinery, will bring disillusionment all round. W. R. E. HARRISON. Buxted, Sussex.

only

ANXIETY AS A CAUSE OF FIBRINOLYSIS

SIR,-The following experiments, carried out between 1939 and 1945, seem to find support in the observations of Dr. Macfarlane and Dr. Biggs (Lancet, 1946, ii, 862) on the relationship between emotional upset and fibrinolysis. 1. Fibrinolysis After Ancesthesia but Before Operation.Blood was collected from three patients who had just received a general anaesthetic and were about to undergo a major operation. A further sample of blood was also collected after the operation. The phenomenon of fibrinolysis was studied in each case according to the technique of Macfarlane. The results are tabulated below.

Immediately after the anaesthetic we have the combined psychological trauma of the expected operation and the general anaesthetic. The actual trauma of operation seems to make the fibrinolysis more pronounced. 2. Fibrinolysis in Emotional Upsets not Associated with Operation.-Blood was examined after collection from patients in various conditions of anxiety. Two had just heard their first air-raid warning, two were suffering from thyrotoxicosis, and three were diagnosed as anxiety states.

The results

were as

follows :

3. Control Experiments.—Samples of blood from fifteen transfusion donors were studied. None of these showed any fibrinolysis, even after a period of some weeks. The number of cases studied is somewhat small and the test employed was of a qualitative nature. Nevertheless, it would seem a fairly clear-cut observation that various conditions of anxiety can produce fibrinolysis. The mechanism wheieby anxiety leads to an increased content of blood fibrinolysin has also been under study. So far it has been shown that the addition of adrenaline to blood does not lead to fibrinolysis. It is also interesting to note that fibrinolysis could not as a rule be reproduced in rabbits by operation or by violent death produced by a sharp blow on the back of the neck. A limited number of experiments, in whicb 1.

Macfarlane, R. G.

Lancet, 1937, i, 10.