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BLOOD TRANSFUSION IN BLACKWATER FEVER.
645
BLOOD TRANSFUSION IN BLACKWATER FEVER. BY G. CARMICHAEL LOW, M.D. EDIN., F.R.C.P. LOND., SENIOR PHYSICIAN, HOSPITAL FOR TROPICAL DISEASES, LONDON, AND SEAMEN’S HOSPITAL, ROYAL ALBERT DOCKS ; CONSULTING PHYSICIAN FOR TROPICAL DISEASES, TILBURY HOSPITAL ;
W. E. COOKE, F.R.C.S. IREL., D.P.H., MEDICAL SUPERINTENDENT, HOSPITAL FOR TROPICAL DISEASES ;
AND
P. H. MARTIN,
B.M.,
B.CH.
OXF.,M.R.C.P. LOND.,
D.T.M. & H., LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE.
(From the Hospital for Tropical Diseases, Endsleighgardens, W.C. 1.)
Present Illness.-In January, 1928, the patient suffered from a series of short attacks (about four in number) of what was called haematuria. He did not go to bed, but went on with his work the whole time. The attacks lasted three or four days to a week, with three to ten days’ intervals. Patient then sailed for England and at first felt fit and well, but a little later he felt feverish once or twice. On Friday morning, March 23rd, he got a chill while on deck and developed a sharp fever. He passed dark-coloured urine that afternoon, and his temperature was 103° F. that night. The ship arrived at Tilbury on March 26th, 1928, and the patient was immediately brought up to the Hospital for Tropical Diseases and admitted at 1 P.M. A cursory examination at once showed that he was suffering from haemoglobinuria (blackwater) and not haematuria. He was desperately ill, deeply jaundiced, anaemic, with a large spleen and a subnormal temperature, 966° F. The pulse was fair. The lungs showed considerable bronchitis, with rales and rhonchi over both bases. A blood count showed the number of red blood corpuscles to be as low as 980,000 per c.mm. ; white blood cells, 7000; haemoglobin, 30 per
cent. ; differential count: polymorphonuclear leucocytes, cent. ; large mononuclear leucocytes, 7 per cent. ; lymphocytes, 26 per cent. ; eosinophils, 0. No parasites. Anisocytosis and poikilocytosis, marked. Urine: dark reddish black colour ; albumin, + + many granular casts and debris ; no red blood corpuscles ; haemoglobin present. Treatment was at once commenced with rest, warmth, fluids, nourishment, and alkalies. The foot of the bed was raised ; milk diluted with soda water, orange water with glucose, barley-water, and sodium bicarbonate in water were given repeatedly in small amounts by the mouth. At 11 P.M. on the night of admission, considering the journey from the dock to the hospital, the patient’s condition 67 per
THERE is
disease in which the prognosis is so blackwater fever, whether treated in the tropics or in England. From time to time practitioners get a series of favourable cases and are then apt to conclude that the success is due, say, to the administration of some special drug. A subsequent unfavourable series, however, causes them to doubt, and warns them not to boast about their previous results. An experience of 28 years, both abroad and at home, leads me to the conclusion that, apart from careful nursing and attention, there is no specific treatment for this disease. Many drugs have been lauded from time to time, only to fall into disfavour and disuse. The main causes of death in blackwater fever are (1) syncope, (2) acute haemolysis, (3) suppression of urine, (4) hyperpyrexia, and (5) asthenia, which produces, perhaps, the most disappointing results. In this type of case the urine clears, yet the patient does not improve, the blood does not regenerate, and gradually a semi-comatose condition supervenes and death takes place. Looking back, one is impressed by our powerlessness to prevent death in such cases. The marrow seems to become exhausted, and no longer capable of producing new blood. In a recent case of this kind we tried to save life by blood transfusion, and so had the opportunity of seeing its effect in stimulating the marrow to renewed life and the formation of fresh blood corpuscles. We had no hesitation about trying this, even considering the possibility of causing more haemolysis, because the patient could not have lived through the night. In a paper on blackwater fever in London,1 MansonBahr and Sayers record a somewhat similar case.
uncertain
They
no
as
say :-
"In
a
recent moribund
case
in whom the urine had
suffering from extreme anaemia, (the blood count showing only 850,000 red cells per c.mm.), blood transfusion of 700 c.cm. of blood was performed, with the result that the patient revived in a miraculous manner and regained consciousness. There was no evidence of any further hsemolysis, and the urine remained clear. Unfortunately the improvement was not maintained and, in spite of a further transfusion, the patient died three days later."
cleared, but who
In this
the authors considered the results thought it was worthy of another suitable case occurred. case
encouraging trial if The
a
was
and
The Present Case Described. history of our case is as follows :-
European, male, aged 50, a planter in British Guiana. Born in England ; went to British Guiana about 1896 and has lived there ever since with the exception of holidays in England, the last of which was four years ago. Previous 7MMesses.—Measles ; no scarlatina, enteric, or rheumatic fever. Many attacks of malaria during the last 25 years; one attack of dysentery. Had an attack of (?) hsematuria, five years ago (1923), and was in hospital six weeks. No definite diagnosis was made. Came to England after this attack and saw a specialist, who could find no cause for the hsematuria. X ray examinations were negative. 1 P. Manson-Bahr and E. G.
i., 273.
Sayers: THE LANCET, 1927,
fair. Since admission at 1 P.M. over 20 oz. of black urine had been passed, which showed evidence of clearing in the later samples. Fluids were being taken well; the pulse was 112, and its volume fair. At 6.30 A.M. next morning the patient showed signs of collapse. The pulse became almost imperceptible at the wrist, and the breathing irregular and of the Cheyne-Stokes type. The mouth and tongue were very dry and sore. Strychnine gr. 1/30 subcutaneously was followed by intravenous glucose 3 viii. at 8 A.M. By 10 A.M. a rapid change for the worse set in, with sweating, pain in the chest, rapid and feeble pulse, and respiration-rate 42. The features became pinched, the eyes dull, and a mucus rattle appeared with respiration, the patient being too weak to cough. Strychnine gr. 1/30 was again given, followed by camphor in oil 1 c.cm. an hour later. Some delay (through no fault of the London Blood Transfusion Service, who in this case, as in all previous cases, have never failed to provide volunteer donors to this hospital at short notice) arose in arranging for a blood donor, and during the interval before his arrival the temporary improvement, which had again followed the stimulants given at 3 P.M., passed off. By 6 P.M. signs of rapid dissolution were present: a semi-conscious state, glazing of the eyes, rattle in the throat, and very feeble pulse. We were unanimous that without blood transfusion death was imminent.
was
II,
The
patient’sblood had previously
been examined and
found as follows : red cells, 980,000 per c.mm. ; haemoglobin, 30 per cent. ; white cells, 7000 ; blood-group III. ; van den Bergh : direct test negative ; indirect test strongly positive -about 22 units. Test for haemolytic system, as found in cases of paroxysmal haemoglobinuria, negative. At 7 P.M., after checking the absence of agglutination of the donor’s cells by the patient’s serum, blood transfusion was started and 400 c.cm. of citrated whole blood was given. During the transfusion a visible improvement took place ; the pulse became stronger, the colour less ashy, the tongue less dry, and at the close of the transfusion the patient succeeded in coughing up mucus from his throat. The urine subsequently passed showed no evidence of any further haemolysis ; 44 oz. of black water had been passed in the first 16 hours in hospital, and contained much albumin and some granular casts. Red blood cells were not seen, but haemoglobin was present. At 10.45 P.M. strychnine was again used to treat a sudden collapse ; the very brief improvement was followed at 11.20 P.M. by another period of collapse. Shortly afterwards the bowels moved in response to an oil enema ; there was a very distinct improvement, the pulse being better and stronger. As the bowels had been confined for some time and, as was discovered later, haemorrhoids caused much pain on def2ecation, it is probable that the collapse was associated with the bowel movement. March 28th : The patient had slept for short periods during the night. He maintained the improvement during the day, but had slight incontinence of fseces and urine with pain on micturition. His general condition remained much the same until the afternoon of the 29th, when he became distressed and appeared to have considerable pain over the f the right chest, where pleuritic friction was audible. l’é):]
646 The application of antiphlogistine gave relief and the condition appeared to resolve. The urine collected for the two periods of 24 hours was 61 oz. and 47 oz. The blood count showed 1,000,000 red cells and haemoglobin 30 per cent. 30th : In the morning the breathing became laboured, the pulse quickened, and the patient appeared more drowsy and weaker. He was coughing up large quantities of sputum. As he was obviously sinking, it was decided to transfuse blood again, and at noon 300 c.cm. of citrated whole blood were given. There was an immediate general improvement, which was maintained throughout the afternoon and evening. 31st: Patient had slept a little during the night, in spite of a distressing cough, and was stronger and mentally brighter by the morning. A blood film showed normoblasts for the first time. A blood count on April 1st showed 1,630,000 red cells and still no parasites, and another, next day, showed 2,200,000 red cells. From April lst onwards the history was one of slow but steady progress. The amount of urine passed daily varied from 60 to 80 oz., the temperature, which had been swinging between 995° F. to 101° F., began to subside, and the cough became less troublesome. Liquor arsenicalis ffli. t.d.s. was started on April 2nd, and was gradually increased. On the 9th " ring" forms of the parasite of subtertian malaria (Plasmodium falciparum) were found for the first time. Quinine hydrochloride gr. i. with iron and arsenic was therefore given three times. On April 10th, tablet plasmochin co., one twice a day, was started, and the iron and arsenic were discontinued. The plasmochin tablets were gradually increased.
his illness, suggest that as a case he would into Group II. as described by G. R. Ross.a Group II. cases are described as those showing definite haemoglobinuria of moderate severity; no suppression ; recovery." These cases show Fouchet’s van den Bergh : test for bile pigments in blood + +. direct—negative ; indirect-5 and 16 units. If placed in this group our patient must have been in the severest attack compatible with inclusion in the group, and were it not for the fact that he was alive, almost untreated, 70 hours from the onset of blackwater, it might be justifiable to place his case in Group III. : " Cases with severe haemoglobinuria: no suppression ; death in 24 to 48 hours." These cases showed Fouchet’s test-)--)- : van den Bergh: direct-negative ; indirect-6 (first day) to 20 units. W. Kikuth3 gives a comprehensive summary of the therapy recorded by various authors in blackwater fever, but no reference to blood transfusion appears. Actual and Theoretical Effects of Blood Transfusion in Blackwater Fever. 1. It undoubtedly treats anoxaemia symptomatically by helping to replenish the patient’s supply of red blood cells. 2. It acts as a stimulus to blood cell formation. There may or may not be an adequate stimulus already provided, but in our case the rise in the number of red cells per cubic millimetre coincided with the time at which blood rejuvenation occurs in other diseases after blood transfusion. 3. The urine in blackwater fever is loaded with albumin. The introduction of healthy blood plasma is probably advantageous. 4. It dilutes the haemoglobin and the bile pigment already free in the plasma, and so may aid the kidney in its work of excretion. 5. It replenishes blood-volume without unduly increasing the amount of sodium chloride. Baker and Dodds4 have shown in their work on obstruction of renal tubules during the excretion of haemoglobin that a percentage of more than about 1 of sodium chloride is a very important factor in causing coagulation of haemoglobin, and therefore tends to cause suppression of urine. Further, Dr. J. G. Thomson, in conversation with one of us (P. H. M.), has recounted how disappointing and sometimes even disastrous were his results in treating blackwater fever in S. This was, of Rhodesia with intravenous salines. course, before the publication of the work of Baker and Dodds in 1925.4 6. It provides the most natural antidote possible to the acidosis and the acid urine which Baker and Dodds have shown in the same paper to be so very important in causing coagulation of the liberated
day of
corne "
I
haemoglobin. It is noteworthy
*
that in our case, in spite of the alkali treatment which was carried out from the start of hospital treatment, the urine was still acid to litmus on the second day-after nearly 24 hours’ treatment. 7. It provides such antibodies as the donor may have in his blood against organisms which are likely to cause intercurrent infection-e.g., lung complications. 8. It does not appear to lead to further haemolysis, provided the bloods are carefully matched. Autoagglutination has been observed by us in severe malarial infections, and demands the utmost care to keep the temperature of the ingoing blood and of the receiving limb as near normal as possible. 9. Whether there is any specific therapeutic action against P. falciparum is very doubtful. It should be noted that neither our patient nor the donor had any quinine in his system at the time of the transfusion. M. Ghiron, in his studies on the pathogenesis of blackwater fever5has demonstrated in
From this date onwards.
The maximum dose of plasmochin co. given was 12 tablets per diem; this dosage was reached gradually from an initial dosage of two tablets per diem. The plasmochin was given in short courses of decreasing length-viz., six, four, and four days-and the intervals of rest from plasmochin co. between each course increased-viz., fiveeight days in this case.
Blood transfusion is not an entirely new line of treatment in blackwater fever, for Manson-Bahr and Sayersl record a case. Nevertheless, the results in 2 our case, considered with the scanty records of other Ross, G. R. : Brit. Jour. Exp. Path., 1927, viii., 442. 3 Kikuth, W. : Arch. f. Schiff- und Tropen-Hygiene, 1927, i., people’s work on this line, appear to justify this 501. somewhat lengthy account of our single case. 4 S. L. Baker and E. C. Dodds : Brit. Jour. Exper. Path., 1925, The clinical condition, combined with the vi., 247. tests of our patient on his admission on the fourth 5 Arch. f. Schiffs- und Tropen-Hyg., 1927, xxxi., 113.
laboratory
I
647 vitro the marked hæmolytic action of blackwater fever serum on quininised red cells, particularly on those from a malarial patient. Transfusion of blood would therefore appear to be inadvisable at a time when the blood of either donor or recipient contains quinine. Prof. Ghiron’s charts suggest that the haemolytic system disappears from the serum of a blackwater fever patient within a month of the attack. Conclusions. In view of the facts brought out by this case, it would seem that transfusion of whole blood at the time of, or immediately after, an attack of blackwater
On the other hand, tumours which to the naked eye appear to be innocent papillomata have, on pathological investigation, shown evidence of invasion. One of the chief methods of treatment of vesical new growth is diathermic cauterisation, the destruction of the growth being performed through an operating cystoscope. Specimens from these cases are not suitable for pathological investigation, so that the diagnosis rests mainly on the cystoscopic appearances. It would therefore not be justifiable to distinguish definitely between simple and malignant tumours on clinical appearances alone. Incidence and Course.
us with a new and useful therapeutic Vesical neoplasm is a fairly common and fatal in the treatment of certain types of this disease. Of 168 cases taken from the records of disease, the usual methods of rest, warmth, finids, and St. Thomas’s Hospital between the years 1914 and alkalis of course being combined. 59 1926 were known to be alive in the latter only Further, our case suggests that the fear of causing year ; 57 had died and the remainder were untraced. more haemolysis should never be allowed to prevent The disease is most common between the ages of blood transfusion in desperate cases of blackwater 65, but two patients in this series were aged fever, and that even in less severe cases transfusion 50 and one being male and one female. It is more 18, be a useful to addition treatment. We feel sure mav that transfusion should not be delayed until a patient 3common in males than females, in the proportion of to 1. The tables show the sex- and ageis moribund, but that even at the last minute it is worthy of trial. The exhibition of tablet plasmochin incidence (Table 1.). TABLE I. co. several days after the initial heemoglobinuria caused no further haemolysis and it was successfully exhibited against the parasites of P. fulcipa.rurr2 when they reappeared in the peripheral blood.
fever, provides measure
SOME ASPECTS OF VESICAL TUMOURS AND THE RESULTS
OF TREATMENT.
BY G. A. Q. LENNANE, M.B. CAMB., M.R.C.S. ENG., Of these 168 cases, only 116 could be traced up to 1926 or till death; 11 additional cases were traced for a time and then lost sight of. Up to the end of 1922, 68 cases were treated for vesical new growth. THIS investigation began in an endeavour to Of these, 59 were traced from the date of their first ascertain the best form of treatment for papilloma of treatment until 1926 or until death. These cases, the bladder, more especially to prevent recurrences, therefore, have a minimum possible post-operative but it soon became evident that other vesical lifetime of at least four years, and (as one first received neoplasms would have to be included. The neoplasms treatment in 1911) a maximum up to 15 years, to which the bladder is susceptible are classified into according to the date on which they first received simple and malignant, the latter being either locally treatment. The period since 1922 is too short to give or generally malignant, according to whether they a fair idea of the comparative fatality of the disease invade the bladder alone or form metastases in other in cases treated after that year. The following table parts of the body. The most important simple shows the number of cases treated up to the end of tumour is the papilloma, which may be sessile or 1922 and the duration of life after the first treatment. pedunculated, varies in size from a small pea to an TABLE II. orange, and possesses long villous processes. Other simple tumours, such as the connective tissue tumours which arise in childhood, adenomata arising in glands at the base, and cholesteatomata, are exceedingly uncommon and none occurred in this series. The malignant growths which attack the bladder are the malignant papilloma, the carcinoma, and the In the malignant papilloma the villi are sarcoma. more stunted and irregular than in the benign form, the bladder wall becomes infiltrated, and the mucous membrane at the base of the tumour adheres to the submucous tissue. Carcinoma of the bladder may be a sessile nodular growth, irregular in appearance, Ddead. L= Living. m=months ; yrs. =years. projecting into the lumen of the bladder, and varying in size from a marble to an orange, or it may be mainly intramural with a few nodules of the surface. Only about half of these patients, therefore, are still Sarcoma is extremely rare and is found only in infancy alive, and of the 30 who are dead 20, or 66 per cent., and late adult life. Only epithelial neoplasms occurred lived less than five years after operation. A large in this series. proportion of deaths occur within six months of The difficulty in diagnosing, in certain cases, treatment. The fatality of this disease is just as between carcinoma and the more malignant forms of strikingly shown in 43 traced patients who received papilloma has made it necessary to include all cases treatment between 1922 and 1926. Only 27 of these of vesical new growth in this investigation. For 43, or 63 per cent., have managed to live four years instance, in some of the cases examined the clinical and many have lived very much less, as some only findings at operation have been those of carcinoma, received treatment in 1925. It must be borne in but on section no pathological evidence of invasion mind that many of these patients have had several has been found. One of the chief reasons for this is treatments, and of those who were still alive in 1926 that, in the specimen removed for pathological many still had symptoms. The two main causes of examination, the base of the tumour has not been cut. death from vesical tumours are haemorrhage and
LATE HOUSE
TO THE SURGICAL UNIT, ST. ASSISTANT MEDICAL OFFICER, QUEEN HOSPITAL FOR CHILDREN, CARSHALTON.
HOSPITAL ;
SURGEON
THOMAS’S MARY’S
N2
BLOOD TRANSFUSION IN BLACKWATER FEVER. BY G. CARMICHAEL LOW, M.D. EDIN., F.R.C.P. LOND., SENIOR PHYSICIAN, HOSPITAL FOR TROPICAL DISEASES, LONDON, AND SEAMEN’S HOSPITAL, ROYAL ALBERT DOCKS ; CONSULTING PHYSICIAN FOR TROPICAL DISEASES, TILBURY HOSPITAL ;
W. E. COOKE, F.R.C.S. IREL., D.P.H., MEDICAL SUPERINTENDENT, HOSPITAL FOR TROPICAL DISEASES ;
AND
P. H. MARTIN,
B.M.,
B.CH.
OXF.,M.R.C.P. LOND.,
D.T.M. & H., LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE.
(From the Hospital for Tropical Diseases, Endsleighgardens, W.C. 1.)
Present Illness.-In January, 1928, the patient suffered from a series of short attacks (about four in number) of what was called haematuria. He did not go to bed, but went on with his work the whole time. The attacks lasted three or four days to a week, with three to ten days’ intervals. Patient then sailed for England and at first felt fit and well, but a little later he felt feverish once or twice. On Friday morning, March 23rd, he got a chill while on deck and developed a sharp fever. He passed dark-coloured urine that afternoon, and his temperature was 103° F. that night. The ship arrived at Tilbury on March 26th, 1928, and the patient was immediately brought up to the Hospital for Tropical Diseases and admitted at 1 P.M. A cursory examination at once showed that he was suffering from haemoglobinuria (blackwater) and not haematuria. He was desperately ill, deeply jaundiced, anaemic, with a large spleen and a subnormal temperature, 966° F. The pulse was fair. The lungs showed considerable bronchitis, with rales and rhonchi over both bases. A blood count showed the number of red blood corpuscles to be as low as 980,000 per c.mm. ; white blood cells, 7000; haemoglobin, 30 per
cent. ; differential count: polymorphonuclear leucocytes, cent. ; large mononuclear leucocytes, 7 per cent. ; lymphocytes, 26 per cent. ; eosinophils, 0. No parasites. Anisocytosis and poikilocytosis, marked. Urine: dark reddish black colour ; albumin, + + many granular casts and debris ; no red blood corpuscles ; haemoglobin present. Treatment was at once commenced with rest, warmth, fluids, nourishment, and alkalies. The foot of the bed was raised ; milk diluted with soda water, orange water with glucose, barley-water, and sodium bicarbonate in water were given repeatedly in small amounts by the mouth. At 11 P.M. on the night of admission, considering the journey from the dock to the hospital, the patient’s condition 67 per
THERE is
disease in which the prognosis is so blackwater fever, whether treated in the tropics or in England. From time to time practitioners get a series of favourable cases and are then apt to conclude that the success is due, say, to the administration of some special drug. A subsequent unfavourable series, however, causes them to doubt, and warns them not to boast about their previous results. An experience of 28 years, both abroad and at home, leads me to the conclusion that, apart from careful nursing and attention, there is no specific treatment for this disease. Many drugs have been lauded from time to time, only to fall into disfavour and disuse. The main causes of death in blackwater fever are (1) syncope, (2) acute haemolysis, (3) suppression of urine, (4) hyperpyrexia, and (5) asthenia, which produces, perhaps, the most disappointing results. In this type of case the urine clears, yet the patient does not improve, the blood does not regenerate, and gradually a semi-comatose condition supervenes and death takes place. Looking back, one is impressed by our powerlessness to prevent death in such cases. The marrow seems to become exhausted, and no longer capable of producing new blood. In a recent case of this kind we tried to save life by blood transfusion, and so had the opportunity of seeing its effect in stimulating the marrow to renewed life and the formation of fresh blood corpuscles. We had no hesitation about trying this, even considering the possibility of causing more haemolysis, because the patient could not have lived through the night. In a paper on blackwater fever in London,1 MansonBahr and Sayers record a somewhat similar case.
uncertain
They
no
as
say :-
"In
a
recent moribund
case
in whom the urine had
suffering from extreme anaemia, (the blood count showing only 850,000 red cells per c.mm.), blood transfusion of 700 c.cm. of blood was performed, with the result that the patient revived in a miraculous manner and regained consciousness. There was no evidence of any further hsemolysis, and the urine remained clear. Unfortunately the improvement was not maintained and, in spite of a further transfusion, the patient died three days later."
cleared, but who
In this
the authors considered the results thought it was worthy of another suitable case occurred. case
encouraging trial if The
a
was
and
The Present Case Described. history of our case is as follows :-
European, male, aged 50, a planter in British Guiana. Born in England ; went to British Guiana about 1896 and has lived there ever since with the exception of holidays in England, the last of which was four years ago. Previous 7MMesses.—Measles ; no scarlatina, enteric, or rheumatic fever. Many attacks of malaria during the last 25 years; one attack of dysentery. Had an attack of (?) hsematuria, five years ago (1923), and was in hospital six weeks. No definite diagnosis was made. Came to England after this attack and saw a specialist, who could find no cause for the hsematuria. X ray examinations were negative. 1 P. Manson-Bahr and E. G.
i., 273.
Sayers: THE LANCET, 1927,
fair. Since admission at 1 P.M. over 20 oz. of black urine had been passed, which showed evidence of clearing in the later samples. Fluids were being taken well; the pulse was 112, and its volume fair. At 6.30 A.M. next morning the patient showed signs of collapse. The pulse became almost imperceptible at the wrist, and the breathing irregular and of the Cheyne-Stokes type. The mouth and tongue were very dry and sore. Strychnine gr. 1/30 subcutaneously was followed by intravenous glucose 3 viii. at 8 A.M. By 10 A.M. a rapid change for the worse set in, with sweating, pain in the chest, rapid and feeble pulse, and respiration-rate 42. The features became pinched, the eyes dull, and a mucus rattle appeared with respiration, the patient being too weak to cough. Strychnine gr. 1/30 was again given, followed by camphor in oil 1 c.cm. an hour later. Some delay (through no fault of the London Blood Transfusion Service, who in this case, as in all previous cases, have never failed to provide volunteer donors to this hospital at short notice) arose in arranging for a blood donor, and during the interval before his arrival the temporary improvement, which had again followed the stimulants given at 3 P.M., passed off. By 6 P.M. signs of rapid dissolution were present: a semi-conscious state, glazing of the eyes, rattle in the throat, and very feeble pulse. We were unanimous that without blood transfusion death was imminent.
was
II,
The
patient’sblood had previously
been examined and
found as follows : red cells, 980,000 per c.mm. ; haemoglobin, 30 per cent. ; white cells, 7000 ; blood-group III. ; van den Bergh : direct test negative ; indirect test strongly positive -about 22 units. Test for haemolytic system, as found in cases of paroxysmal haemoglobinuria, negative. At 7 P.M., after checking the absence of agglutination of the donor’s cells by the patient’s serum, blood transfusion was started and 400 c.cm. of citrated whole blood was given. During the transfusion a visible improvement took place ; the pulse became stronger, the colour less ashy, the tongue less dry, and at the close of the transfusion the patient succeeded in coughing up mucus from his throat. The urine subsequently passed showed no evidence of any further haemolysis ; 44 oz. of black water had been passed in the first 16 hours in hospital, and contained much albumin and some granular casts. Red blood cells were not seen, but haemoglobin was present. At 10.45 P.M. strychnine was again used to treat a sudden collapse ; the very brief improvement was followed at 11.20 P.M. by another period of collapse. Shortly afterwards the bowels moved in response to an oil enema ; there was a very distinct improvement, the pulse being better and stronger. As the bowels had been confined for some time and, as was discovered later, haemorrhoids caused much pain on def2ecation, it is probable that the collapse was associated with the bowel movement. March 28th : The patient had slept for short periods during the night. He maintained the improvement during the day, but had slight incontinence of fseces and urine with pain on micturition. His general condition remained much the same until the afternoon of the 29th, when he became distressed and appeared to have considerable pain over the f the right chest, where pleuritic friction was audible. l’é):]
646 The application of antiphlogistine gave relief and the condition appeared to resolve. The urine collected for the two periods of 24 hours was 61 oz. and 47 oz. The blood count showed 1,000,000 red cells and haemoglobin 30 per cent. 30th : In the morning the breathing became laboured, the pulse quickened, and the patient appeared more drowsy and weaker. He was coughing up large quantities of sputum. As he was obviously sinking, it was decided to transfuse blood again, and at noon 300 c.cm. of citrated whole blood were given. There was an immediate general improvement, which was maintained throughout the afternoon and evening. 31st: Patient had slept a little during the night, in spite of a distressing cough, and was stronger and mentally brighter by the morning. A blood film showed normoblasts for the first time. A blood count on April 1st showed 1,630,000 red cells and still no parasites, and another, next day, showed 2,200,000 red cells. From April lst onwards the history was one of slow but steady progress. The amount of urine passed daily varied from 60 to 80 oz., the temperature, which had been swinging between 995° F. to 101° F., began to subside, and the cough became less troublesome. Liquor arsenicalis ffli. t.d.s. was started on April 2nd, and was gradually increased. On the 9th " ring" forms of the parasite of subtertian malaria (Plasmodium falciparum) were found for the first time. Quinine hydrochloride gr. i. with iron and arsenic was therefore given three times. On April 10th, tablet plasmochin co., one twice a day, was started, and the iron and arsenic were discontinued. The plasmochin tablets were gradually increased.
his illness, suggest that as a case he would into Group II. as described by G. R. Ross.a Group II. cases are described as those showing definite haemoglobinuria of moderate severity; no suppression ; recovery." These cases show Fouchet’s van den Bergh : test for bile pigments in blood + +. direct—negative ; indirect-5 and 16 units. If placed in this group our patient must have been in the severest attack compatible with inclusion in the group, and were it not for the fact that he was alive, almost untreated, 70 hours from the onset of blackwater, it might be justifiable to place his case in Group III. : " Cases with severe haemoglobinuria: no suppression ; death in 24 to 48 hours." These cases showed Fouchet’s test-)--)- : van den Bergh: direct-negative ; indirect-6 (first day) to 20 units. W. Kikuth3 gives a comprehensive summary of the therapy recorded by various authors in blackwater fever, but no reference to blood transfusion appears. Actual and Theoretical Effects of Blood Transfusion in Blackwater Fever. 1. It undoubtedly treats anoxaemia symptomatically by helping to replenish the patient’s supply of red blood cells. 2. It acts as a stimulus to blood cell formation. There may or may not be an adequate stimulus already provided, but in our case the rise in the number of red cells per cubic millimetre coincided with the time at which blood rejuvenation occurs in other diseases after blood transfusion. 3. The urine in blackwater fever is loaded with albumin. The introduction of healthy blood plasma is probably advantageous. 4. It dilutes the haemoglobin and the bile pigment already free in the plasma, and so may aid the kidney in its work of excretion. 5. It replenishes blood-volume without unduly increasing the amount of sodium chloride. Baker and Dodds4 have shown in their work on obstruction of renal tubules during the excretion of haemoglobin that a percentage of more than about 1 of sodium chloride is a very important factor in causing coagulation of haemoglobin, and therefore tends to cause suppression of urine. Further, Dr. J. G. Thomson, in conversation with one of us (P. H. M.), has recounted how disappointing and sometimes even disastrous were his results in treating blackwater fever in S. This was, of Rhodesia with intravenous salines. course, before the publication of the work of Baker and Dodds in 1925.4 6. It provides the most natural antidote possible to the acidosis and the acid urine which Baker and Dodds have shown in the same paper to be so very important in causing coagulation of the liberated
day of
corne "
I
haemoglobin. It is noteworthy
*
that in our case, in spite of the alkali treatment which was carried out from the start of hospital treatment, the urine was still acid to litmus on the second day-after nearly 24 hours’ treatment. 7. It provides such antibodies as the donor may have in his blood against organisms which are likely to cause intercurrent infection-e.g., lung complications. 8. It does not appear to lead to further haemolysis, provided the bloods are carefully matched. Autoagglutination has been observed by us in severe malarial infections, and demands the utmost care to keep the temperature of the ingoing blood and of the receiving limb as near normal as possible. 9. Whether there is any specific therapeutic action against P. falciparum is very doubtful. It should be noted that neither our patient nor the donor had any quinine in his system at the time of the transfusion. M. Ghiron, in his studies on the pathogenesis of blackwater fever5has demonstrated in
From this date onwards.
The maximum dose of plasmochin co. given was 12 tablets per diem; this dosage was reached gradually from an initial dosage of two tablets per diem. The plasmochin was given in short courses of decreasing length-viz., six, four, and four days-and the intervals of rest from plasmochin co. between each course increased-viz., fiveeight days in this case.
Blood transfusion is not an entirely new line of treatment in blackwater fever, for Manson-Bahr and Sayersl record a case. Nevertheless, the results in 2 our case, considered with the scanty records of other Ross, G. R. : Brit. Jour. Exp. Path., 1927, viii., 442. 3 Kikuth, W. : Arch. f. Schiff- und Tropen-Hygiene, 1927, i., people’s work on this line, appear to justify this 501. somewhat lengthy account of our single case. 4 S. L. Baker and E. C. Dodds : Brit. Jour. Exper. Path., 1925, The clinical condition, combined with the vi., 247. tests of our patient on his admission on the fourth 5 Arch. f. Schiffs- und Tropen-Hyg., 1927, xxxi., 113.
laboratory
I
647 vitro the marked hæmolytic action of blackwater fever serum on quininised red cells, particularly on those from a malarial patient. Transfusion of blood would therefore appear to be inadvisable at a time when the blood of either donor or recipient contains quinine. Prof. Ghiron’s charts suggest that the haemolytic system disappears from the serum of a blackwater fever patient within a month of the attack. Conclusions. In view of the facts brought out by this case, it would seem that transfusion of whole blood at the time of, or immediately after, an attack of blackwater
On the other hand, tumours which to the naked eye appear to be innocent papillomata have, on pathological investigation, shown evidence of invasion. One of the chief methods of treatment of vesical new growth is diathermic cauterisation, the destruction of the growth being performed through an operating cystoscope. Specimens from these cases are not suitable for pathological investigation, so that the diagnosis rests mainly on the cystoscopic appearances. It would therefore not be justifiable to distinguish definitely between simple and malignant tumours on clinical appearances alone. Incidence and Course.
us with a new and useful therapeutic Vesical neoplasm is a fairly common and fatal in the treatment of certain types of this disease. Of 168 cases taken from the records of disease, the usual methods of rest, warmth, finids, and St. Thomas’s Hospital between the years 1914 and alkalis of course being combined. 59 1926 were known to be alive in the latter only Further, our case suggests that the fear of causing year ; 57 had died and the remainder were untraced. more haemolysis should never be allowed to prevent The disease is most common between the ages of blood transfusion in desperate cases of blackwater 65, but two patients in this series were aged fever, and that even in less severe cases transfusion 50 and one being male and one female. It is more 18, be a useful to addition treatment. We feel sure mav that transfusion should not be delayed until a patient 3common in males than females, in the proportion of to 1. The tables show the sex- and ageis moribund, but that even at the last minute it is worthy of trial. The exhibition of tablet plasmochin incidence (Table 1.). TABLE I. co. several days after the initial heemoglobinuria caused no further haemolysis and it was successfully exhibited against the parasites of P. fulcipa.rurr2 when they reappeared in the peripheral blood.
fever, provides measure
SOME ASPECTS OF VESICAL TUMOURS AND THE RESULTS
OF TREATMENT.
BY G. A. Q. LENNANE, M.B. CAMB., M.R.C.S. ENG., Of these 168 cases, only 116 could be traced up to 1926 or till death; 11 additional cases were traced for a time and then lost sight of. Up to the end of 1922, 68 cases were treated for vesical new growth. THIS investigation began in an endeavour to Of these, 59 were traced from the date of their first ascertain the best form of treatment for papilloma of treatment until 1926 or until death. These cases, the bladder, more especially to prevent recurrences, therefore, have a minimum possible post-operative but it soon became evident that other vesical lifetime of at least four years, and (as one first received neoplasms would have to be included. The neoplasms treatment in 1911) a maximum up to 15 years, to which the bladder is susceptible are classified into according to the date on which they first received simple and malignant, the latter being either locally treatment. The period since 1922 is too short to give or generally malignant, according to whether they a fair idea of the comparative fatality of the disease invade the bladder alone or form metastases in other in cases treated after that year. The following table parts of the body. The most important simple shows the number of cases treated up to the end of tumour is the papilloma, which may be sessile or 1922 and the duration of life after the first treatment. pedunculated, varies in size from a small pea to an TABLE II. orange, and possesses long villous processes. Other simple tumours, such as the connective tissue tumours which arise in childhood, adenomata arising in glands at the base, and cholesteatomata, are exceedingly uncommon and none occurred in this series. The malignant growths which attack the bladder are the malignant papilloma, the carcinoma, and the In the malignant papilloma the villi are sarcoma. more stunted and irregular than in the benign form, the bladder wall becomes infiltrated, and the mucous membrane at the base of the tumour adheres to the submucous tissue. Carcinoma of the bladder may be a sessile nodular growth, irregular in appearance, Ddead. L= Living. m=months ; yrs. =years. projecting into the lumen of the bladder, and varying in size from a marble to an orange, or it may be mainly intramural with a few nodules of the surface. Only about half of these patients, therefore, are still Sarcoma is extremely rare and is found only in infancy alive, and of the 30 who are dead 20, or 66 per cent., and late adult life. Only epithelial neoplasms occurred lived less than five years after operation. A large in this series. proportion of deaths occur within six months of The difficulty in diagnosing, in certain cases, treatment. The fatality of this disease is just as between carcinoma and the more malignant forms of strikingly shown in 43 traced patients who received papilloma has made it necessary to include all cases treatment between 1922 and 1926. Only 27 of these of vesical new growth in this investigation. For 43, or 63 per cent., have managed to live four years instance, in some of the cases examined the clinical and many have lived very much less, as some only findings at operation have been those of carcinoma, received treatment in 1925. It must be borne in but on section no pathological evidence of invasion mind that many of these patients have had several has been found. One of the chief reasons for this is treatments, and of those who were still alive in 1926 that, in the specimen removed for pathological many still had symptoms. The two main causes of examination, the base of the tumour has not been cut. death from vesical tumours are haemorrhage and
LATE HOUSE
TO THE SURGICAL UNIT, ST. ASSISTANT MEDICAL OFFICER, QUEEN HOSPITAL FOR CHILDREN, CARSHALTON.
HOSPITAL ;
SURGEON
THOMAS’S MARY’S
N2