928

PSEUDOHYPERKALÆMIA IN ACUTEMYELOID LEUKÆMIA

SIR,-Dr Fennelly and his colleagues (Jan. 5, p. 27),who described a patient with acute lymphatic leukaemia andhyperkalsmia, suggested that the excess of potassium inplasma might have originated from the leuksemic tissueand be set off by the " lytic

" action of the antileukaemictreatment. We have investigated a patient with acutemyeloid leukaemia (type: promyelocyte II), in whom wefound pseudohyperkalaemia. In this case the source of theadditional potassium was the peripheral white-cell mass,and potassium was released from the cells in vitro, notin vivo.

A 34-year-old man had an enlarged spleen and liver and a veryhigh white-cell count. On admission the lower tip of the spleenwas palpable about 4 cm. below the umbilicus and the liver about8 cm. below the costal margin. The white-cell count was 580,000,the red-cell count 2,400,000, and the platelet-count 135,000,70-80% of the leucocytes belonged to the myeloid series, themajority being promyelocytes n. However, a number of moremature granulocytes could also be seen-i.e., hiatus leuksmicuswas absent. A marrow aspirate contained some white-cell andred-cell precursors, and the morphology of these cells wassimilar to those found in the peripheral blood. The first diagnosiswas chronic myeloid leukaemia with an acute paramyelocyticcrisis, and busulphan treatment was started. There was no

improvement, and the number of younger cells in the bloodincreased. Busulphan was abandoned, and vincristine and

prednisolone were started. This new treatment produced someimprovement, the number of white-cells falling and the spleenbecoming somewhat smaller. However, the beneficial effect wasshort-lived, and the treatment had to be repeated again and again.The patient was treated for 219 days in the department, duringwhich time he received 10 courses of antileukxmic treatment.The last three included also cytosine arabinose and rubidomycin.He died in cardiac failure.

During his stay in the ward the electrolyte content of theblood was frequently measured, and sodium was found to be135-141 meq. per litre, and potassium 3-7-4-2 meq. per litre.6 days before his death the potassium was very high (10-2 meq.per litre). The test was repeated, and again a high value wasobtained. Since the patient did not show any symptoms ofhyperkalaemia, investigation of the source of the increasedpotassium was started (see table). A blood-film showed red cells3,400,000 per c.mm., white cells 456,000 per c.mm. (promyelo-cytes and other granulocytes 82%, lymphocytes 14%, eosinophils2%, monocytes 2%), platelets 40,000 per c.mm.

Up to 15 minutes after the blood-taking the potassiumcontent of the plasma did not rise. However, the serum-potassium rose 30 minutes after venepuncture, and 2hours later it increased even more. The plasma-potassiumrose when his white cells were incubated after centrifuga-tion both in his own plasma and in a control plasma. Thered cells did not release potassium in either their ownplasma or a control plasma. Platelets seemed unlikelyto be the source of increased potassium.

The potassium contents of the washed white and redcells after wet ashing were higher than in the controlbut lower than values found by others. I, The patient diedbefore we were able to finish our investigations.

Flahavan et al. found higher potassium levels in lympho-blasts of patients with acute lymphoblastic leuksmia.

They do not mention hyperkalaemia.It is not clear whether the high potassium content of

the leukxmic cells and the release of this electrolyte into theplasma at the terminal stage of the disease is a result ofthe antileuksemic treatment, but this is a possibility. Weshould like to draw attention to the fact that this release

may occur after the cells have been taken out of the circula-tion-i.e., in vitro. When investigating hyperkalasmia inleukaemia this must be kept in mind.The control platelets and white blood-cells were kindly

supplied by the Hungarian Transfusion Centre.

2nd Department of Medicine,Semmelweis University,Budapest, Hungary.

BELA RINGELHANNELÖD LASZLOLIDIA VAJDA.

ACUTE MYELOBLASTIC LEUKÆMIA AFTERPROPYLTHIOURACIL

SiR,-After propylthiouracil treatment, agranulocytosis 3and aplastic anxmia 4 have been reported; but leukaemiahas not yet been recorded. We have seen a patient withacute myeloblastic leukaemia which followed propylthiou-racil therapy.The patient, a 74-year-old housewife, was admitted with

palpitations, dyspnoea, weakness, and fatigue. Three yearspreviously Graves’ disease had been diagnosed by the

family physician on clinical findings. She had been treatedwith 50 mg. of propylthiouracil three times daily forapproximately two years. Her palpitations disappearedcompletely. Nearly a year before admission another

hospital treated her for cardiac insufficiency with Natig-oxine ’. Two months before admission she started againto take 50 mg. of propylthiouracil three times daily.On admission investigations were as follows:Red blood-cells 3,200,000 per c.mm.; hxmoglobin 9-3 g. per

100 ml.; hsematocrit 30%, platelets 86,000 per c.mm.; whiteblood-cells 120,000 per c.mm. (1% neutrophilic band form, 3-5%neutrophilic metamyelocytes, 0-5% neutrophilic myelocyte, 94%myeloblasts, and 1 % lymphocytes); bone-marrow aspirate fromsternum was hypercellular with 92% myeloblasts, 0-5% neutro-

1. Baron, D. N. Clin. Chem. 1972, 18, 320.2. Flahavan, E., Smyth, H., Thormes, R. D. Br. J. Cancer, 1973,

28, 354.3. Martello, O. J., Katims, R. B., Yunis, A. A. Archs intern. Med.

1967, 120, 587.4. Aksoy, M., Erdem, S. Lancet, 1968, ii, 1379.

POTASSIUM LEVELS OF PATIENT’S BLOOD CONSTITUENTS

I I

929

philic myelocytes, 4% neutrophilic metamyelocytes, 3% neutro-philic band forms, 0-5% orthochromatic normoblasts. Mitotic

elements 4-5%. Fetal haemoglobin 1%., serum-iron 140 !g. per100 ml., serum-cholesterol 90 mg. per 100 ml., uric acid 6-8 mg.per 100 ml. Basal metabolic rate -9-91%. Radioactive iodine

(1311) uptake: 1 hr. 7%, 24 hr. 6%, 48 hr. 6%.Acute myeloblastic leukxmia was diagnosed and com-

bined therapy with corticosteroid, mercaptopurine, andvincristine was started. The patient was transfused severaltimes. Despite this, her condition deteriorated and shedied from bleeding.

Propylthiouracil may depress granulocytopoiesis and

occasionally depresses the bone-marrow. We are inclinedto think that, in our patient with acute myeloblasticleukxmia, this antithyroid agent was possibly one of thefactors leading to the blood disorder.

Section of Hæmatology,Internal Clinic of

Istanbul Medical School,Capa, Istanbul, Turkey.

MUZAFFER AKSOYSAKIR ERDEMHIKMET TEZELTUNA TEZEL.

IMMUNOLOGICAL FEATURES OF

WEGENER’S GRANULOMATOSISSIR,-We read the letter by Dr Fauci and Dr Wolff

(April 13, p. 688) and await with interest their papers in thepress. Although corticosteroids have been shown to

deplete lymphocytes and to inhibit cell-mediated immunereactions in animal models, 1,2 the evidence that therapeuticdoses of corticosteroids in man suppress delayed hyper-sensitivity reactions is at best inconclusive. 3-6 6 The briefreview cited by Fauci and Wolff clearly indicates that,although early reports suggest suppression in some patients,later reports usually failed to confirm this finding. A pointthat seemed to have been overlooked is that delayed hyper-sensitivity responses were absent in 4 of our 5 patients whohad not received steroids.A possible reason for the difference between our results

and those of Fauci and Wolff 11 may lie in the clinical statusof the patients. Many of their patients were in partial orcomplete remission at the time skin tests were carried out,whereas all our patients had active disease. We think thatpatients with active disease are more likely to reveal abasic abnormality than patients who are in a therapeuticallyinduced remission.We wish to emphasise that skin tests alone do not provide

an adequate assessment of cell-mediated immunity. Inthe only published paper on the subject at the time wecompleted our manuscript,8 the only tests of delayed hyper-sensitivity which seem to have been performed were skintests with S.K.S.D. and mumps antigen. In addition to skintests we carried out lymphocyte transformation and macro-phage migration inhibition studies with 4 antigens andP.H.A. and found a significant impairment of lymphocytetransformation, both in the presence of antigens and withthe mitogen. This was associated with an apparently intactmacrophage migration inhibition. The defect was seen inboth treated and untreated patients, and the response toP.H.A. in our untreated cases ranged from 9-6% to 72%of normal.The role of immune complexes in the xtiology of

1. Harris, S., Harris, T. N. Proc. Soc. exp. Biol. Med. 1950, 74, 186.2. Osgood, C. K., Favour, C. B. J. exp. Med. 1951, 94, 415.3. Harvier, P., Camus, J. L., Deuil, R., Di Matteo, J. J. franç. Med.

Chir. Thor. 1951, 5, 164.4. Marie, J., Cruciani, C. Presse méd. 1952, 60, 829.5. Truelove, L. H. Br. med. J. 1957, ii, 1131.6. Toh, B. H., Roberts-Thompson, I. C., Mathers, J. D., Whittingham,

S., Mackay, I. R. Clin. exp. Immun. 1973, 13, 55.7. Gabrielsen, A. E., Good, R. A. Adv. Immun. 1967, 6, 92.8. Fauci, A. S., Wolff, S. M., Johnson, J. S. Now Engl. J. Med. 1971,

285, 1493.

Wegener’s granulomatosis is unclear. Methods for

detecting circulating immune complexes remain imperfect,but they were not found in 8 of our 10 patients tested bythe anti-complementary method.9 We agree that this doesnot exclude the possibility that immune complexes mightbe localised in the kidneys, although in the case-historiesquoted by Dr Fauci and Dr Wolff this was not consideredan important finding. Indeed, in one of them there was apreponderance of fibrin and very little globulin,to andfibrin was also found in this type of lesion, in the absenceof either immunoglobulin or complement.ll

In Wegener’s granulomatosis it is of course possiblethat, as in leprosy 12 and the well-known animal model oflymphocytic choriomeningitis,13 there is a spectrum ofdifferent clinicopathological patterns, in some of which adepression of cell-mediated immunity might be associatedwith or followed by immune complex deposition.

Guy’s Hospital,London SE1 9RT.

E. J. SHILLITOET. LEHNERM. H. LESSOFD. F. N. HARRISON.

CO-TRIMOXAZOLE AND THE BLOOD

SIR,-Although the adverse effects of co-trimoxazolehave attracted comment, 14,1.5 they seem to be more frequentand serious than is realised. Of 112 patients with megalo-blastic anaemia investigated in this department during1972 and 1973, 108 had deficiencies of folate, vitamin B12,or both. Co-trimoxazole appeared to be a precipitatingfactor in the remaining 4 (3-6%).

Case 1.-A pregnant woman aged 31 presented with iron-defi-ciency anaemia (Hb 8.0 g. per 100 ml., mean corpuscular volume63 fl., mean corpuscular haemoglobin 20-4 pg.). After treatmentwith parenteral iron, her hxmoglobin rose to 9-8 g. (M.C.V. 9-1 fl.,M.C.H. 28-7 pg.). She was then given two courses of co-trimoxazole(9’60 g. each) for urinary-tract infection. Hxmoglobin fell to8-3 g. per 100 ml. and M.C.V. rose to 103 fl. Erythropoiesis wasmegaloblastic. Folic acid was given for 10 days without improve-ment. It was discovered that a third course of the antibacterial(9-60 g.) had been prescribed concurrently with the folic acid.When it was stopped the reticulocyte count rose and anaemiaimproved.

Case 2.-Pharyngo-laryngo-oesophagectomy was performedupon a woman aged 70 years. Three weeks after operation herhaemoglobin was 11-1 g. per 100 ml. (M.C.V. 89 fl., M.C.H.29-9 pg.). A chest infection developed and she was given co-trimoxazole (total dose 13-44 g.) for one week. Eight days laterthe hxmoglobin level had fallen to 7-3 g. per 100 ml. (M.C.V.89 fl., M.C.H. 30 pg.) with neutropenia (2100 per c.mm.) andthrombocytopenia (5000 per c.mm.). A blood-film showedneutrophil hypersegmentation and a few macrocytes. Althoughhypocellular, the marrow showed megaloblastic changes. She wasgiven parenteral folic acid and the blood picture soon returned tonormal.

Case 3.-A woman of 83 was given two courses of co-trimoxazole(total dose 19-20 g.) for urinary-tract infection. The haemoglobinlevel fell from 12-9 g. to 11-4 g. per 100 ml. and the M.C.V. rosefrom 97 fl. to 110 fl. during six weeks in hospital. Erythropoiesiswas megaloblastic. She died of bronchopneumonia before theblood condition could be treated effectively.

Case 4.-A man of 81 with chronic congestive heart-failure and

9. Mowbray, J. F., Hoffbrand, A. V., Holborow, E. J., Seah, P. P.,Fry, L. Lancet, 1973, i, 400.

10. Roback, S. A., Herdmann, R. C., Horger, J., Good, R. A. Am. J.Dis. Child. 1969, 118, 608.

11. Paronetto, F. in Textbook of Immunopathology (edited by P. A.Miescher, H. J. Muller-Eberhard); p. 722. New York and London,1969.

12. Turk, J. L. in Immune Complex Diseases (edited by L. Bonomoand J. L. Turk); p. 165. Milan, 1970.

13. Hirsch, M. S., Murphy, F. A., Hicklin, M. D. J. exp. Med. 1968,127, 757.

14. Lancet, 1973, ii, 950.15. Hamblin, T. J. ibid. p. 1153.