T H E AMERICAN JOURNAL OF CLINICAL PATHOLOGY Vol. 35, No. 5, pp. 413-419 May, 1961 Copyright © 1961 by The Williams & Wilkins Co. Printed in U.S.A. TRANSFUSION OF POSTMORTEM HUMAN BLOOD JACK KEVORKIAN, M.D., AND GLENN W. BYLSMA, M.D. Department of Pathology, Pontiac General Hospital, Pontiac, Michigan Nine months ago we first became aware of a startling idea which led to the preliminary work recorded here. We were surprised to learn that for 30 years Russian medical men have been successfully transfusing cadaver blood as casually as we dispense whole blood taken from living donors.3 • 4 I t is a natural tendency merely to shrug the matter off as something which could never be performed or regarded as worthwhile in our country (see addendum). Because baseless rejection is unjustified, we decided to investigate for ourselves. The idea has an ostensible undercurrent of repugnance which makes it difficult to view objectively; but it also has obvious advantages. Before elucidating these pro and con factors, we present 4 cases of our own in which cadaver blood was transfused into living human recipients. METHOD Mutilation of the neck is to be avoided in handling corpses. We tried to follow the procedure outlined by the Russians, and, therefore, started the project by performing femoral phlebotomy under aseptic surgical conditions. Inasmuch as we were using vacuum bottles, available at any donor station, it seemed more reasonable to use either the internal or external jugular vein (preferably on the right because of direct innominate drainage) as the site for simple venipuncture. We now do this routinely. The skin is prepared by cleaning with a hexachlorophene solution and tapwater, followed by application of 2 or 3 per cent tincture of iodine. Blood should be drawn within 6 hr. after Received, July 11, 1960; revision received, August 5; accepted for publication February 2, 1961. Dr. Kevorkian was a fourth year resident in Pathology at Pontiac General Hospital. Dr. Bylsma is an Associate Pathologist at Pontiac General Hospital. 413 death. Death must have been sudden and rather unexpected in order to assure adequate natural fibrinolysis and a minimal content of toxic or therapeutic ingredients in the blood. An autopsy must be performed in order to establish absence of contagious or other potentially hazardous disease. The body is placed on a tilt table and the head lowered so that the supine form assumes an angle of at least 30 degrees. Regulation pint vacuum bottles containing anticoagulant acid citrate dextrose (ACD) solution are used with sterile plastic tubes with attached needles (blood collection set). Flow should be smooth and steady if death was very sudden and fast. Occasionally death is more protracted and agonizing than it seems, and the flow then often slows down because small postmortem clots may partially block the needle lumen. Slight twisting or slow readjustment of the needle within the vein usually re-establishes adequate flow. Blood remaining in the plastic collecting tube at the end of the drawing is used for hemogram studies and for bacterial culture. Other samples for serology, cross matches, and pertinent chemical analysis can be obtained at necropsy. R E P O R T O F CASES Case 1 The donor was a 51-year-old white man who died suddenly while mowing his lawn. Three pints of blood were drawn from the left external jugular vein, the last just 6 hr. after his collapse. Autopsy revealed coronary occlusion with infarction. Donor blood was group 0, Rh positive (CDE). VDRL was negative; hemoglobin 18.1 Gm. per 100 ml.; hematocrit reading, 53 per cent; white cell count, 6350 per cu. mm.; serum K, 13.6 mEq. per 1.; serum Na, 140 mEq. per 1.; glucose, 119 mg. per 100 ml.; blood urea nitrogen, 34.3 mg. per 100 ml.; 414 K E V O R K I A N AND BYLSMA Vol. 35 cholesterol, 342 mg. per 100 ml. Blood mg. per 100 ml. Autopsy permission was not granted. culture was negative after 36 days. The recipient was an 82-year-old white Case 2 woman with severe arteriosclerotic encephalomalacia and mental aberrations, The donor was a 44-year-old white man uremia, and pancytopenia. Her blood was who, as a passenger in an automobile, was group 0, Rh positive (cDE) and was killed in an accident. A penetrating wound compatible with donor blood on cross was noted over the right zygoma which, at match. Shortly after her admission to the autopsy, was continuous into the brain. hospital the following determinations were One pint of blood was drawn 4 ^ hr. after performed on the recipient's blood: VDRL, death from the left external jugular vein, negative; hemoglobin 7.3 Gm. per 100 ml.; and another pint an hour later from the hematocrit reading, 19.5 per cent; white right internal jugular vein. Each pint cell count 2850 per cu. mm.; platelet count, yielded 470 ml. of packed cells after settling 84,000 per cu. mm.; reticulocyte count, for 11 days (a total of 940 ml. of packed normal; serum K, 4.98 mEq. per 1.; serum cells from 2 pints). Na, 139.5 mEq. per 1.; serum CI, 111.8 Donor blood was group O, Rh negative mEq. per 1.; urea nitrogen 70 mg. per (cde). VDRL was negative; hemoglobin, 100 ml. 20.4 Gm. per 100 ml.; hematocrit reading, Urinalysis revealed a specific gravity of 58 per cent; white cell count, 11,800 per cu. 1.016, mild albuminuria (25 mg. per 100 mm.; serum K, 13 mEq. per 1.; serum Na, ml.), and 25 to 30 red and 10 white blood 145 mEq. per 1.; serum CI, 93.2 mEq. per 1.; thymol turbidity, 2.45 Maclagan units; cells per high power field. One pint of cadaver blood was transfused heterophile agglutination, negative. Blood slowly a few hours after admission. There culture was negative until the blood was was no reaction. The patient's hemoglobin used (11 days after drawing), and 2 interrose to 7.75 Gm. per 100 ml., red cell count vening subcultures to blood agar were also ' to 2.8 million per cu. mm., and her hema- negative. tocrit reading to 22 per cent. The recipient was a 78-year-old white man A second pint of cadaver blood was given with arteriosclerotic heart disease and the next morning, again without reaction. congestive failure. Carcinoma of the cecum A blood culture drawn from the recipient or appendicial abscess was also suspected. shortly afterward was negative for 19 days His rectal temperature was 103.8 F. The recipient's blood was group 0, Rh positive and was then discarded. The third pint of cadaver blood (250 ml. (cDe); hemoglobin on admission, 6.3 Gm. packed cell volume) was administered 1 day per 100 ml.; hematocrit reading, 23 per after the second pint. The patient had had a cent; red cell count, 3 million per cu. mm.; fever of 100 to 101 F. (rectal) for 2 days white cell count, 13,000 per cu. mm. (96 which spiked to 104.6 F. several hours after per cent polymorphonuclear leukocytes); the last packed cell transfusion. Urine from VDRL, negative; serum K, 3.8 mEq. per an indwelling Foley catheter remained 1.; serum Na, 140 mEq. per 1.; nonprotein clear amber, and her supernatant blood nitrogen, 65 mg. per 100 ml. serum also remained clear. The following There were 25 red cells and 50 white cells determinations were performed 2 days later per high power field in the urine. This (immediately before the recipient's death): microscopic hematuria was again detected hemoglobin, 10.7 Gm. per 100 ml.; hema- 2 days later, at which time the recipient's tocrit reading, 29 per cent; red cell count, hemoglobin was 6.6 Gm. per 100 ml.; 2.73 million per cu. mm.; serum K, 4.32 hematocrit reading, 23 per cent; red cell mEq. per 1.; serum Na, 147 mEq. per 1.; count, 2.4 million per cu. mm.; and nonserum CI, 125.6 mEq. per 1.; blood urea protein nitrogen 117 mg. per 100 ml. nitrogen 162 mg. per 100 ml.; blood sugar Three days later (5 days after admission) 206 mg. per 100 ml.; serum cholesterol, 114 he received 470 ml. of packed cadaver cells May 1961 T R A N S F U S I O N O F POSTMORTEM without reaction. Rectal temperature was 101.2 F. Ten hours later his hemoglobin was 7.3 Gm. per 100 ml., hematocrit reading, 26 per cent. The next day he was given the other unit of packed cadaver cells (470 ml.). There was no reaction; rectal temperature remained stable at 100 F. Nine hours later the recipient's hemoglobin level was 9.7 Gm. per 100 ml. with a hematocrit reading of 32 per cent. Supernatant serum remained clear. Three days later, his hemoglobin level was 9.15 Gm. per 100 ml. The recipient died 8 days after transfusion of the last unit of packed cells. Autopsy was not permitted. Case 3 The donor was a 46-year-old white man who was dead on arrival at the emergency room. One full pint of blood was drawn from the right internal jugular vein 5 ^ hr. after death. Much clotted blood was observed within large vessels at autopsy 6 hr. later. Death was owing to coronary occlusion with very early infarction. Donor blood was group A, Rh negative, (cde). VDRL was negative; hemoglobin, 20.4 Gm. per 100 ml. with a hematocrit reading of 60 per cent; white cell count 12,600 per cu. mm.; serum K, 24 mEq. per 1.; serum Na, 151 mEq. per 1.; serum CI, 101 mEq. per 1.; blood sugar, 227 mg. per 100 ml.; urea nitrogen 14.7 mg. per 100 ml.; cholesterol, 350 mg. per 100 ml. Blood culture was negative for 19 days (at which time the blood was used), and 3 previous subcultures were negative. The recipient was a 56-year-old white woman with severe nutritional and iron deficiency anemia and carcinoma of the cecum with metastases. She was having frequent loose tarry stools, estimated to contain from 100 ml. to 200 ml. of whole blood per day. The patient was alert, cheerful, and ambulatory. Her blood was of group A, Rh positive (cDe). VDRL was negative; hemoglobin on admission was 8.4 Gm. per 100 ml., with a hematocrit reading of 26 per cent; white cell count was 7750 per cu. mm. Urinalysis revealed innumerable red cells per high power field, but no gross hematuria. 415 BLOOD She received 1000 ml. of conventional bank blood on the day of admission, and another unit of conventional blood the next day. On the following day (2 days after admission) her hemoglobin level was 10.9 Gm. per 100 ml. with a hematocrit reading of 36 per cent. Two days later she received a single unit of cadaver blood without reaction. On the following day her hemoglobin level was 11.9 Gm. per 100 ml. with a hematocrit reading of 37 per cent. There was no evidence of fresh hemolysis in her serum. The patient was discharged the next day feeling quite well. Case 4The donor was a small, eumorphic, 12year-old white boy, 56 in. tall, who drowned. He was submerged for about 12 min. and was dead on arrival at the emergency room. All resuscitative efforts were fruitless, including an injection of intracardiac epinephrine. At autopsy the esophagus was observed to be full of lake water, but there was very little in the stomach. Lungs were well expanded without evidence of edema or water. Two full units of blood were drawn at 2 ^ and 3 hr. after death from the right internal jugular vein using the method described above. Blood was of group A, Rh positive (CDe); VDRL, negative; hemoglobin, 12.3 Gm. per 100 ml.; hematocrit reading, 40 per cent; white cell count, 8900 per cu. mm.; sugar, 198 mg. per 100 ml.; and blood urea nitrogen (BUN), 11.2 mg. per 100 ml. Blood culture taken at the end of drawing manifested no growth in 2 weeks and no growth in subcultures to blood agar at 10 and 14 days. The recipient was a 41-year-old colored woman who had a "strawberry sore" on the buccal mucosa. Her hemoglobin at the time of admission was 9.1 Gm. per 100 ml. Biopsy of the lesion was performed. The next day her hemoglobin was 8.2 Gm. per 100 ml.; and the hematocrit reading was 26 per cent. VDRL and urinalysis were negative; nonprotein nitrogen (NPN) was 23 mg. per 100 ml. The recipient's blood was group A, Rh positive (cDe). One pint of 416 K E V O R K I A N A N D BYLSMA cadaver blood was given (after 19 days of storage). The patient was irritable and crying while venipuncture was being performed. There was absolutely no reaction during transfusion. The next morning her hemoglobin was 9.7 Gm. per 100 ml.; hematocrit reading, 33 per cent. Later that morning, 250 ml. of packed cadaver cells (from the second unit) were given just prior to surgery for total removal of the buccal lesion. Her hemoglobin rose to 11.0 Gm. per 100 ml. with a hematocrit reading of 37 per cent. The following day they were recorded at 10.6 Gm. per 100 ml. and 34 per cent, respectively. The patient's supernatant serum remained completely free of evidence of hemolysis after each transfusion. She tolerated them well, is now alert, cheerful, comfortable, and has been discharged. COMMENTS Because embalming is required before burial in this country, and the procedure involves removal of blood which is washed down the drain, and especially because a nonmutilating needle is used to remove blood from the jugular vein, we feel justified in stating that permission of next of kin is not necessary if corpse blood is to be taken. At any rate, in our opinion, it should never be taken if autopsy is not assured, thereby making concern over specific permission to remove blood totally superfluous. Physicians were notified of the source of our blood. We believe that such notification is not essential, because if the entire procedure of cadaver blood transfusion is performed correctly, there is no need for undue anxiety or precaution on the part of any physician. It seems a matter of good taste and trust, nevertheless, to make the patient's physician aware of the source. Routine consent from the recipient is no more necessary than in instances of conventional bank blood transfusions. The use of cadaver blood is by no means an experimental procedure—having been widely practiced in Russia for 30 years (see addendum) . The relatively high potassium and NPN content of cadaver blood might seem to be Vol. 35 major disadvantages, but the somewhat elevated sugar certainly is not detrimental. Also, it would seem that cadaver erythrocytes might be more fragile owing to a few hours of postmortem life within the vessels of the dead organism, and that their functional capacity might be reduced or destroyed. Finally, by using such blood, one might run the risk of introducing nebulous or as yet undiscovered "toxins" into a recipient's blood stream. Most of these objections are more imaginary than real—a sort of emotional reaction to a new and slightly distasteful idea. No such "toxins" have been detected. Our 8 pints (on a short-term basis) and over 27,000 transfusions in Russia bear this out. Not a single hint of a reaction or other ill effect was observed by us personally on very close clinical observation, despite the fact that 2 of the patients were already moribund and very toxic and none of the 4 had any anti-allergic therapy. Supernatant serum of drawn blood ranged from clear to evidence of mild hemolysis in our series. Hemolysis occurred chiefly in instances of repeatedly intermittent flow owing to tiny obstructing clots, but it was never significantly more conspicuous than the degree seen in some instances of usual donor blood. In no instance did the degree of hemolysis visibly increase with storage. No evidence of increased in vivo fragility was noted after transfusion; the recipient's supernatant serum remained clear, and the urine revealed no hemoglobin content. The Russians claim to have demonstrated the persistence of red and white cell functions in cadaver blood drawn in accordance with certain stipulations which we followed. Chromium-51 isotope studies to corroborate the Russians' claims and to demonstrate adequate red cell survival would perhaps be interesting. Finally, stored blood of any kind, whether from the corpse or the living, always has an increased potassium and NPN content owing to minimal continual cellular disintegration. In 2 instances the serum K level was 13 mEq. per 1.; it was 24 mEq. per 1. in the third. These determinations May 1961 T R A N S F U S I O N O F POSTMORTEM BLOOD were performed on blood taken at the time of drawing or at necropsy shortly thereafter. No determinations were made during storage, but they will be performed as this project continues. We believe that the changes in K level of cadaver blood simulate those in routine donor blood, which may reach 30 mEq. per 1. after storage for 3 weeks, but which are also reversible.2 Once transfused, the somewhat aberrant chemical pattern is evidently soon remedied by dilution and by the metabolic systems of the recipient, even if he is in the dire agony of approaching death, provided there is no severe renal dysfunction. Advantages are noteworthy. Cadaver blood always raises the hemoglobin level and hematocrit value of the recipient to a degree comparable to that of conventional bank blood. No reaction was noted in 4 patients receiving a total of 8 pints. A single cross match will make available for immediate use several pints of the same blood for any individual patient; this reduces the number of possible antigens introduced into a patient requiring multiple transfusions, and saves the technician's time. The blood is free—requiring no remuneration either on the part of the hospital or the coroner—where an autopsy is routine in instances of relatively sudden death. Such blood would otherwise have been washed down the drain and obviously have required no replacement. The only financial consideration involved is the time of a special technician (if any) and the cost of equipment used (bottles, bags, and tubes—all of which are inexpensive). It is ideal for prolonging the life of "hopelessly" ill patients or victims of emergencies requiring immediate massive amounts of blood. Although carrier state can not be conclusively ruled out, it is blood offering the least possible chance for transmission of infectious hepatitis—"pure" in that one has detailed gross and microscopic autopsy verification of the donor's state of health and of each individual organ. The technic of obtaining it is simple, and it is stored and dispensed exactly as is conventional donor blood. CONCLUSIONS AND 417 RECOMMENDATIONS 1. Cadaver blood is perfectly suitable for transfusion into living human donors. With due precautions and with autopsy control, the procedure is innocuous and beneficial. It is a successful form of homotransplantation—no more objectionable than is the use of cadaver corneas, skin, vessels, or bone, and probably more often beneficial. 2. The blood should be drawn within 6 hr. after death. This may be performed in the autopsy room, for only a simple venipuncture is necessary. It should be stored according to United States blood banking regulations and used within 21 days after acquisition. 3. It should be drawn from a neck vein (preferably the right internal jugular) with the body in a head-down tilted position. Because small postmortem clots may occasionally limit the total drawn, larger bore needles might facilitate flow. We are now in the process of testing these to improve our yield. 4. Under proper clinical conditions, cadaver blood is ideal for "hopelessly" ill patients, for those requiring massive emergency transfusions, for priming pump and dialysis machines, for indigent patients (the blood is qualitatively equal to conventional blood, but less expensive), and for anyone requiring correction of anemia or many sporadic transfusions who is willing to take it. 5. Any cadaver blood program should be under the direct supervision and control of the pathologist who examines the corpse, performs the autopsy, and supervises the blood bank. He should lead an unofficial "cadaver blood team" trained to perform this task efficiently when the opportunity arises. Such opportunities are infrequent, and they could not be a major source for blood banks, but larger centers may supply excessive amounts of cadaver blood to smaller hospitals where it can be used but is not easily acquired. 6. Any apparently healthy person who dies suddenly is a candidate for donation. Complete autopsy must be assured. Ideal instances involve closed injuries or internal catastrophes, such as heart attacks, strokes, 418 K E V O R K I A N AND BYLSMA drowning, suffocation, and even acute alcoholic intoxication.3 Minor cuts and occasional deep penetrating trauma are not contraindications as long as there has been no extensive hemorrhage. 7. It would be presumptuous to recommend widespread institution of this novel procedure. Nevertheless we are now convinced of its merit and practicality, and are indebted to the Russian investigators who blazed the trail. From our limited experience, we know it can do no harm and that it offers tremendous potential good which warrants widespread and thorough investigation. ADDENDUM Shortly after submitting this paper, we learned that approximately 35 pints of cadaver blood were transfused in Chicago in 1935 to 1936. Unfortunately the endeavor was not recorded in the literature until this year.1 The program at that time was regarded as a success, but was supplanted by the newly begun live donor system. SUMMAKIO I N INTEBLINGUA 1. Sanguine ab cadaveres es preferctemente usabile in transfusiones ad in vive recipientes human. Le procedimento es innocue e benefic si executate con circumspection sub conditiones de necropsia surveliate. Illo es un forma successose de transplantation homologe e non es plus objectionabile que le uso de corneas, pelle, vasos, o osso ab cadaveres. Illo es probabilemente plus frequentemente benefic que le altere mentionate transplantationes. 2. Le sanguine debe esser obtenite intra sex horas pos' morte. Le labor pote esser effectuate in le sala del necropsias, proque non plus que un simple venepunctura es requirite. Le sanguine debe esser magasinate secundo le regulationes del statounitese bancas de sanguine. Illo debe esser usate intra 21 dies. 3. Le sanguine debe esser prendite ab un vena del collo (preferibile-mente le vena jugular dextero-interne) con le corpore in postura inclinate, capite in basso. Viste que micre coagulas de formation post morte Vol. 85 reduce a vices le rendimento total, agulias de calibre major es possibilemente a recommendar pro facilitar le fluxo. Currentemente nos testa tales pro determinar le possibilitate de un meliorate rendimento. 4. Sub appropriate conditiones clinic, le sanguine de cadaveres es ideal pro patientes qui es desperatemente malade, qui require massive transfusiones de urgentia, e qui es indigente (sed iste sanguine es qualitativemente equal a illo obtenite ab fontes conventional). Iste sanguine es etiam utile in le preactivation de pumpas e dialysatores. De facto, illo pote esser usate in non importa qual patiente requirente le correction de anemia o multiple transfusiones sporadic pro altere rationes, providite que ille es preste a acceptar lo. 5. Omne programma de utilisation de sanguine de cadaveres debe esser placiate sub le surveliantia directe del pathologo qui examina le mortos, executa le necropsias, e se occupa del banca de sanguine. Iste experto debe esser le chef de un "team pro sanguine de cadavere," con membros trainate a executar le requirite mesuras efficacemente quandocunque le opportunitate se presenta. Tal opportuniatates es infrequente. Illos non pote devenir un fonte major in le provision del bancas de sanguine, sed le centres major poterea sin dubita suppler lor excessos a minor hospitales ubi illo pote esser usate sin esser facile a obtener. 6. Omne apparentemente non-morbide subjecto qui mori subitemente es un candidate pro le donation. Un complete necropsia debe esser assecurate. Casos ideal es illos de injurias non-aperte o de catastrophes interne como attaccos cardiac, syncopes, necation, suffocation, e mesmo acute intoxication alcoholic. Minor incisiones e etiam trauma a penetration profunde non es contraindicationes, providite que nulle extense hemorrhagia ha occurrite. 7. II esserea un presumption voler recommendar le extense adoption de iste nove methodo. Tamen, nos es nunc convincite de su merito e de su practicalitate e es obligate al investigatores russe qui ha preparate le via. Super le base de nostre limitate experientia nos sape que le methodo non pote esser nocive sed que illo possede un tremende po- May 1961 T R A N S F U S I O N O F POSTMORTEM BLOOD tential de beneficientia que justifica extense e detaliate investigationes. Acknowledgments. Technical assistance was provided by Miss B. Glaysher, Mr. E. Bea, Mr. S. Meda, and Mr. H. Watkins. We are grateful to those clinicians who cooperated on the wards, and especially to Dr. John J. Marra, Director of Laboratories, for permitting us to perform this project and for encouragement during the work. 419 REFERENCES 1. FARMER, D . F . : Transfusions of cadaver blood. A contribution to the history of blood transfusions. Bull. A.A.B.B., 13: 229-234, 1960. 2. MOLLISON, B. L.: Blood Transfusion in Clinical Medicine. Springfield, 111.: Charles C Thomas, 1956, p. 23. 3. BETEOV, B. A.: Transfusion of cadaver blood. Surgery, 46: 651-655, 1959. 4. YUDIN, S. S.: Transfusion of cadaver blood. J. A. M. A., 106: 997-999, 1936.
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