Edinburgh Medical Journal

November 1924

REPORT ON THE TREATMENT OF ANEMIA BY ADMINISTRATION OF SPLEEN AND RED BONE-MARROW EXTRACT.

By H. B. PORTEOUS, M.B., Ch.B.

(From the Department of Therapeutics, University of Edinburgh.) THE treatment of anæmias by the administration of bone. marrow, in spite of the favourable reports given by Fraser,2 Billing, and Whait during the last decade of the nineteenth century, has not been placed on a definite scientific basis up to the present. C. D. Leake and his co-workers 5, 6, 7, 8, during the last two years, have endeavoured to place this subject on a rational foundation. Their findings are as follows: The injection of freshly-prepared saline extracts of red bone marrow into the ear veins of rabbits caused in each case an immediate rise in the number of circulating erythrocytes; this rise was maintained during the period of administration of the extract, but on its cessation the count fell to normal in about two days. A similar extract was prepared from spleen, as Danilewsky and Selensky had shown that extracts of this organ have some hæmopoietic action when injected intraperitoneally. The results obtained from this extract differed somewhat from the previous in that a preliminary fall was succeeded by a rise rather less marked than that obtained by the injection of bonemarrow extract, but persisted longer after the discontinuance of the injections. The hæmoglobin also increased, but not in proportion to the rise in the number of erythrocytes, but this increase continued for a longer period. The administration of these extracts by the mouth produced similar results. On combining the extracts there was a greater increase in the number of erythrocytes than by either alone, and on cessation

Erythrocytes

CASE 1.-Miss J. C., aged 70. Post-hæmorrhagic Anemia.

Tubes showing no

Hæmolysis

Patient

Tubes showing
Hæmolysis

Patient

The tops of the columns indicate the tubes showing complete Hæmolysis. A broken topped column indicates Hemolysis not complete in last tube taken.

of the administrations there was a return to normal in about five days.

The effect on the number of circulating leucocytes seemed to point to an "alternating stimulation," in that when a rise in the number of leucocytes was conspicuous, the erythrocytes did not increase to the same extent, and vice versa. Similar results were obtained when normal humans were made the subjects of like experiments, the combined extracts being administered in the dried form in capsules containing 0.3 grams.

The following is a report of the results obtained in a clinical test of the above extracts, which were kindly provided by Professor Leake. Four cases were treated, and the results obtained are portrayed graphically in the accompanying figures. In addition to the cell counts and hæmoglobin estimations the fragility of the patient's corpuscles to hypotonic salt solution was estimated throughout the course of treatment, to discover whether there was any alteration in the resistance of these cells consequent upon treatment. The method used was slightly

modified from that of Giffin and Sandford, a definite amount of an emulsion of washed corpuscles being added to tubes containing a series of hypotonic salt solutions ranging from 0.5 per cent. to 0.28 per cent. in steps of 0.02 per cent. The results are compared with normal corpuscles and are expressed as initial hæmolysis-the tube showing the slightest tinge of hæmoglobin in the supernatant fluid after the corpuscles had settled-and complete hæmolysis, where there was no turbidity on shaking the tube. The height of the column in the diagram is an expression of the resistance of the corpuscles to hæmolysis. Twelve tubes were used in each case, numbered from 25 to 14; tube 25 containing the least dilute solution and 14 the most dilute.

CASE I.-Miss J. C., aged 70. The patient was admitted with a history of epigastric pain of only a few days' duration, and a hæmatemesis the day before admission. On admission there was melæna with dark, tarry stools. She was very anæmic and rather emaciated. Other examinations suggested the presence of a gastric ulcer.

For twelve days she received no specific treatment for her anæmia, being on special diets for her gastric condition. During this time her erythrocyte count rose, but the percentage of hæmoglobin altered very slightly. She was then put on iron in the form of Pil. aloes et ferr., but little effect was produced on her blood-count and hæmoglobin

Erythrocytes

CASE II.-Mrs J. A., aged 43. Chlorotic type of Anæmia.

FRAGILITY TEST:

Tubes showing no
Hæmolysis

Patient

estimation. At the end of a week the iron was stopped and the combined extracts given in doses of 0.3 grams. before meals, and as the curve shows (Fig. 1), there was a gradual increase in the number of erythrocytes, and in the first week a slight rise in the hæmoglobin. The leucocyte count was rather variable; the first rise was probably due to the fact that the patient had just had a meal before the blood was drawn off, and the second large rise occurred during an acute arthritis of the knee which cleared up under local treatment. The fragility test showed from the first an increased resistance to complete hæmolysis as compared with normal corpuscles, though the initial. hæmolysis was the same as normal. During the treatment the corpuscles showed increased resistance.

Case II.-Mrs J. A., aged 43. This case was admitted suffering from auricular fibrillation and acute failure of the right side of the heart. She was wasted and anæmic. Her cardiac condition responded well under digitalis and quinidine therapy before treatment for her anæmic condition was instituted. This was a chlorotic type of anæmia with a low colour index. Iron was given as in the previous case from the 10th of March, and though the erythrocyte count was very little altered, there was an immediate rise in the percentage of hæmoglobin. In the second week the erythrocyte count was slightly higher, but the hæmoglobin did not continue to rise at the rate at which it began. On the 24th March the combined extracts of spleen and bone marrow were commenced and the iron was stopped. As shown in Fig. 2, there was a slight increase in the erythrocyte count, a more marked increase in the leucocyte count, whilst the hæmoglobin increased by 12 per cent. During the two weeks following the hæmoglobin continued to rise but not so rapidly, the erythrocyte and leucocyte count hovered around the same level. There was, however, during the last week of this treatment a slight falling off in all the counts and in the amount of hæmoglobin, though not pronounced.

This case from the first showed a markedly increased resistance to hæmolysis which persisted throughout unaltered.

CASE III.-Mrs C. R., aged 60. The patient was admitted with a history of diarrhoea of several months' duration, becoming more severe during the month preceding admission. She also occasionally vomited what she had just taken. The day before admission she had severe melæna and passed large clots of blood. In appearance she was apathetic and markedly anæmic; the skin showed a yellowish tinge not amounting to true jaundice. There was some epigastric tenderness, and a tumour could be made out in the left hypochondrium. A test meal showed no free acid. This case was under observation for several weeks before specific treatment was commenced. At first