1379

have been reduced if the

or chair.
St. James Hospital,

patients had remained confined to bed

ALEXANDER KAHAN.

Balham, London S.W.12.

SIR,-Dr. Spencer, in his interesting paper last week,

does not mention the blood-uric-acid levels of the two patients
who died. Hyperuricxmia is an invariable accompaniment of
the fasting state, and the only two patients I have treated by
this method achieved blood-levels of 105 and 15.6 mg. per
100 ml. Could hyperuricæmia sensitise the myocardium to the
action of catecholamines ?
Church Hill,
A. M. W. PORTER.
Camberley, Surrey.
APLASTIC ANÆMIA AFTER
PROPYLTHIOURACIL

SIR,—Antithyroid drugs (thiouracil, methylthiouracil, propylthiouracil, methimazole, and carbimazole) are usually
listed among agents associated with the development of
agranulocytosis, but bone-marrow aplasia rarely2 follows
their use.3—5 The only case of aplastic anxmia which has been
described after propylthiouracil therapy is the one recently
reported by Martelo et al.But, though their patient had bone
marrow aplasia with pancytopenia, the clinical course was "more
in keeping with that of agranulocytosis in the authors own
"

of aplastic anaemia with

manifestations which followed propyl-

words. We report here

severe

hmmorrhagic

typical

case

thiouracil therapy.
The patient, a 39-year-old man, was admitted to this
department with weakness, fatigue, palpitation, weight-loss,
pallor, epistaxis, and petechiæ. Two months before he had
been diagnosed as having Graves disease and treated with
propylthiouracil in another hospital. In 3 weeks, he had
received 80 x 50 mg. tablets of this drug. A week after stophe had begun to complain of epistaxis
and weakness, for which he had been treated with bloodtransfusions without much success.
At admission the patient was well developed but looked
very pale and tired, with purpuric spots all over his body.
He had pronounced exophthalmos and moderate diffuse

ping propylthiouracil,

thyroid enlargement. Blood-pressure (B.P.) was 125/50 mm.

Hg.; pulse-rate regular, 119 beats per minute; temperature
37°C.

Investigations were as follows: red blood-cells (R.B.C.)

1,350,000 per c.mm.; haemoglobin 35 g. per 100 ml.; packedcell volume 13%; platelets 10,800 per c.mm.; white bloodcells 2600 per c.mm. (14% segmented neutrophils, 8% neutrophilic band forms, 10% monocytes, and 68% lymphocytes);
bone-marrow aspirates from sternum and iliac crest were
hypocellular with 62% lymphocytes, 8% neutrophilic myelocytes, 10% neutrophilic metamyelocytes, 6% neutrophilic
band forms, 4% segmented neutrophils, 1% plasma cells, 1%

polychromatic macroblasts, 7% polychromatic normoblasts,

and 1 % orthochromatic normoblasts; foetal haemoglobin
5-7%, serum-iron 180;jt.g. per 100 ml., serum-cholesterol 135
mg. per 100 ml., serum-protein-bound-iodine 7.5µg. per 100
ml., basal metabolic rate +58%. No agglutination could be
demonstrated in the leucoagglutinin and platelet-agglutinin
tests,7performed with and without propylthiouracil, using
patients serum, with drug concentrations of 20, 30, and 40
(l.g. per 100 ml.
Aolastic anaemia due to oroovlthiouracil

was

diasnosed.

1. Thomson, T. J., Runcie, J., Miller, V. Lancet, 1966, ii, 992.

2. Trotter, W. R. J. New Drugs, 1962, 2, 333.
3. Burrell, C. D. Br. med. J. 1956, i, 1456.
4. Levine, B., Rosenberg, D. V. Ann. intern. Med. 1954, 41, 844.
5. Poate, H. R. G. Med. J. Aust. 1957, ii, 208.
6. Martelo, O. J., Katims, R. B., Yunis, A. A. Archs intern. Med. 1967,
120, 587.
7. Dausset, J., Colombani, J., Okochi, K. Leukocyte and Platelet Agglutination Immunological Methods; p. 539. Philadelphia, 1964.
8. Harrington, W. J., Minnich, V., Arimura, A. K. Progress in Hæmatology; p. 166. New York, 1956.

Despite energetic treatment, which consisted of seven wholeblood transfusions in 3 weeks, the last two in plastic bags,
250 mg. methyltestosterone ( Testoviron) weekly, and 12
x 0-5 mg. tablets of dexamethasone daily, R.B.c. count increased
only to 2,130,000 per c.mm., haemoglobin to 56 g. per 100
ml., and platelets to about 100,000 per c.mm. In the meantime, an episode of sore throat was treated with penicillin.
Unlike the case reported by Martelo et al.,6 spontaneous
clinical and haematological improvement did not follow discontinuation of propylthiouracil. Now, about 2 months after
stopping propylthiouracil, the condition of the patient is very
critical.
Hxmorrhagic manifestations (epistaxis, bleeding
from the gums, and widespread purpuric spots) dominate
the clinical picture.
The pathogenesis of drug-induced aplastic anaemia is still
obscure.9 No satisfactory evidence supporting an immune
mechanism could be obtained from experimental investigations. No leucocyte or platelet agglutinins could be found in
our patient or in the patient of Martelo et al.6 Our patient
received a moderate dose of propylthiouracil, daily and overall.
Therefore it seems likely that the amount of the drug that he
received did not play a significant role. Overall haematological
side-effects occur in roughly 1-5% of patients treated with
propylthiouracil, and there is no consistent relation between
the dosage and the occurrence of haematological side-effects.10
It seems likely that their occurrence depends on personal
susceptibility rather than on the quantity of drug used. The
available evidence does

not

enable

us to

personal susceptibility might involve

process as yet undetermined.

Section of Hæmatology,
2nd Internal Clinic of Istanbul Medical School,

Istanbul, Turkey.

which, but this

essential metabolic

say

some

MUZAFFER AKSOY
SAKIR ERDEM.

TONSILLECTOMY AND ADENOIDECTOMY

SIR,—I am grateful to Dr. Alpert and his colleagues (last

week, p. 1319) for confirming my impression that the mortality
figures which they gave for the operations of tonsillectomy and
adenoidectomy had been calculated before they drafted their
original letter (May 25, p. 1149) and for explaining their
estimations in detail. They have been sadly misled by accepting
all the figures on which their calculations were based. Perhaps
they had some right to assume that figures quoted in the
Hospital In-Patient Enquiry would be completely accurate,
but a calculation giving a mortality figure of 1 in 1355 is so
clearly erroneous that it is surprising that it was cited without
any attempt at verification, and that it has been repeated despite
the figures which I gave in my letter.
It is now known that a few hospitals committed fundamental
errors in submitting their returns to the Hospital In-Patient
Enquiry, and it has been verified that almost all of the few
patients recorded in the survey as having died after these
operations are in fact very much alive and well. It is not a case,
as Dr. Alpert and his colleagues now suggest, that some of
these deaths have been attributed to other events-they just
did not occur at all. As a result, the ratio which they calculated
so precisely has no basis in reality. A careful analysis of all
possible sources of information, including those referred to by
Dr. Alpert and his colleagues, has been undertaken by the
General Register Office and, as pointed out previously, these
figures show that in the last three years for which there are
records available there have been an average of 7 deaths per
year at a rate of 1 in approximately 27,000 operations.
It is unfortunate that any erroneous figures should be
included in an official publication, but I think it is possible to
understand how they could find their way into a large volume
packed with statistics. It is not so easy to understand the uncritical acceptance of such figures by workers submitting a
critical apppraisal of the results of these operations.
D. RANGER.
London W.I.
9. Wintrobe, M. M. Clinical Hæmatology;
10. Bartels, E. C. Am. J. Med. 1948, 5, 48.

p. 785. Philadelphia, 1967.