BLOOD TRANSFUSIONS

The first detailed description of a blood tranfusion appeared in 1615, when Andreas Libravius - a chemist, physician and director of the College at Coburg - wrote of how he transfused human blood from a young man into a weak elderly patient by means of silver tubes from the artery of the donor to the artery of the recipient(1) - which resulted in, as Libravius wrote "the warm and spirited arterial blood of the healthy person flows into the ill person and imparts to him the fountain of life and drives away all faintness"(2).

In 1654, Franseco Folli - a physician of Florence, Italy - inserted a silver tube into the artery of an animal (as the donor) and connected the tube to a cannula of bone by an isolated segment of bone(3). Nine years later, in 1663, Timothy Clarke - physician to King Charles II - transfused blood into animals which had been drained of blood(4). In 1665, Richard Lower tried to transfer blood from the jugular vein of a dog to the jugular vein of another dog, but the blood immediately clotted in the tube and blocked its own passage due to the slow movement of the venous blood. Lower went on to try other methods. He opened the jugular vein, and drew out the blood  of a medium sized dog - into which he transfused blood from an artery of a large mastiff dog. As the recipient dog became "overfilled" with infused blood, Lower drained the blood off and repeated the procedure several times - transfusing blood from the mastiff into the smaller dog, then draining off the blood... The constant withdrawl of blood from the mastiff led to it dying. Lower repeated his first series of experiments with a second mastiff - which also died(5). Dr Edmund King - a member of the Royal Society - tried, in 1667, to transfuse blood from the vein of a calf into the vein of a sheep - little or no blood flowed from the calf`s vein into the sheep(6).

Jean-Baptiste Denis - physician to Louis XIV of France - had transfused blood from calves into dogs(7) before, in 1667, he performed four animal-to-human blood transfusions. His first human recipient was transfused with the blood of a sheep - and according to a testimony, recovered. The second case was a volunteer, who was paid for undergoing the trial - but this raised opposition from French physicians. In Denis`s third case, the transfusion merely delayed the death of the recipient. The fourth recipient was Antoine Mauroy - a house-servant - who was transfused with blood from a calf and, as he appeared to show signs of improvement, was given a second transfusion from the artery of a calf into a vein in his arm - but Mauroy suffered from pain in the kidney region, felt a sensation in his chest, and had an irregular heart beat. Two months later, Mauroy became maniacal and his wife insisted on a further transfusion - but the attempt failed and Mauroy died. Denis was tried for manslaughter but was exonerated. As the opponents of animal-to-human blood transfusions included members of the Faculte de Medicin in Paris, the practice was made illegal, and ten years later, the French Parliament prohibited transfusion of blood in human beings throughout France(8).

On 23 Nov 1667, Lower and King arranged for a blood transfusion - to change a person`s character! The idea was that the patient - a 22-year old man, with a brain that was "a little too warm" - could be given the blood of a docile animal - a sheep. The blood transfusion went ahead in front of a large audience, including physicians. Blood was drained out of a cut in the vein of the arm of the patient,and then blood from the carotid artery of a sheep was transfused - by means of silver tubes connected by quills - into the patient. After the procedure, Lower remarked that the patient "found himself very well"(9). Although many more experiments followed in England - the recipients often died(10) and the Royal Society saw little value in blood transfusions(11).

In Germany, Balthauser Kaufmann and Matthaus Purmann transfused blood from sheep into two soldiers - with no improvement(12).

With failures in France, England and Germany, blood transfusions were abandoned(12), and no blood transfusions were attempted during the 18th century.

James Blundell - an obstetrician at St Thomas`s and Guy`s Hospitals in London - became interested in blood transfusions, having witnessed women going into shock and dying from haemorrhage within a few days of giving birth, and in 1818 he published a paper advocating that blood transfusions should only be used when haemorrhaging endangered life. He also warned against transfusing blood from one species to another - and then set out to "prove" this by conducting animal experiments(12) - even though clinical experience had already demonstrated this(13). Blundell performed a human blood transfusion in 1818. Blood from several human donors was transfused into a terminally-ill patient, who died 56 hours later(14). Five years later, in 1823, Blundell referred to having performed five human-to-human blood transfusions - two died at the time of transfusion, and a third was dying(15). Blundell did not report his first "success" until 1828(16). Out of his total of 10 blood transfusions, only four were "successful"(17) - in spite of his animal experiments.

Prior to Blundell`s first human blood transfusion, William Hewson had studied blood coagulation in a test-tube, and published his findings in 1774(19). His investigations had dealt with the effects of neutral salts on plasma globulins - including fibrongen, and had found that salt defibrillated blood - thus preventing clotting(20).

In 1821, Jean Louis Prevost and Jean Dumas - phsyiologists in France - conducted a series of animal experiments(21) - the results of which included finding that blood from which fibrinogen had been removed could be used to revive dogs - Hewson had found this, in vitro, almost 50 years earlier(22).

Defibrillated blood was used in human blood transfusions - in 1830, Dieffenbach transfused defibrillated blood through the umbilical vein of a new-born baby - who died(22); in 1832, Blasius transfused a new-born baby - without success(23); in 1866, Friedberg transfused two patient, poisoned by carbon dioxide, with defibrillated blood - one died the evening of the transfusion, the other died less than three hours after the transfusion(24); in 1867, Bennecke transfused umbilical blood into the umbilical vein of a new-born baby, who survived - but when he tried a repeat transfusion, the baby died(25). But after these failures, there was a successful transfusion of defibrillated blood - in 1873, Sir Thomas Smith, at St Bartholomew`s Hospital, London, reported on his use in the case of a new-born baby suffering from a haemorrage disease(26).

Despite the clinical attempts at human-to-human blood transfusions, there were still those who held on to the belief in animal-to-human blood transfusions. Gesellius - a physician and surgeon of the Royal College of Physicians, in Wilna, Poland - believed that defibrillation removed a vital function from the blood and opposed its use. Instead he supported the use of blood from sheep in transfusions, as he recorded in 1873(27). A year later, in 1874, Oscar Hasse - a physician of Nordhausen, Germany - gave his own support to sheep-to-human blood transfusions(28) and transfused blood from sheep into 15 people - some of whom died, others suffered from various reactions - including difficulties in breathing, unconsciousness, severe chills, vomiting, diarrhoea, coughing, and blood in urine leading to jaundice(29). The dangers of animal-to-human blood transfusions were presented in to the Association of Baltic Physicians in 1874 by Emil Ponfick - from a clinical experience in which a woman had died after receiving blood from a sheep(30). The next year, Ponfick transfused sheep blood into dogs - merely "confirming" the previous clinical findings of others(31). Statistical data was presented in 1875 by Leonard Landois - professor of physiology, University of Griefswald - of 478 authenticated transfusions up to the end of 1874. Of 129 animal-to-human blood transfusions - 62 had shown no improvement or had died, 25 had dubious reports of temporary "improvement", 42 had, according to their authors, shown signs of recovery of improvement; of 347 human-to-human blood transfusions - 150 "improved", 12 had dubious reports of temporary "improvement", 180 were "unfavourable", two died, and the results for the remaining three were unknown(32). Although Landois had conducted his own animal experiments - transfusing blood from one species to another - he was highly critical of the likes of Gesellius and Hasse and their advocating animal-to-human blood transfusions. In fact, Gesellius and Hasse had held back progress by their endorsement of a dangerous method(33).

Attention to trying to overcome the problems of blood clotting were attempted by John Braxton Hicks by chemical methods(34). In 1868, Hicks reported using sodium phosphate mixed with the blood of a donor in experiments on animals(35). When, a year later, he tried sodium phosphate in humans patients, they all died of shock(36). Others began to use citrates in animal experiments(37). In 1894, Sir Almoth E Wright - a pathologist - wrote an article on blood coagulation - and although he avoided the issue of the therapeutic value of reducing coagulation in experiments on animals(38), he did report that clotting time in animals was only rarely increased when citrate was injected, whilst concentrations of calcium ions in the blood was still above the level that caused convulsions(39) - thus, animal experiments did not show that citrates were safe.

Although animal experimenters had found that injecting sodium citrate failed to prevent circulating blood from curdling, in vitro tests showed that a small quantity of citrate made a litre of human blood incoagulable. In 1914, Hustin of Belgium, introduced a certain amount of citrate into a human patient and found that it did not produce abnormally low concentration of calcium in the blood of the recipient(40).

With the discovery that sodium citrates could be safely used human patients - and the discovery of human blood groups in test-tube studies of human blood by Karl Landsteiner of the Institute of Pathological Anatomy, University of Vienna, Austria, in 1900-01(41,42) - L Agote of Buenos Aires conducted his first human blood transfusion with citrated blood on 9 Nov 1914. Five days later, he transfused a second patient - both were successful(43) - but it was not until 1915 that Agote`s work appeared in the medical press(44). Independently of Agote, Richard Lewisohn - a New York surgeon - published the results of his indirect transfusion with sodium citrated blood in 1915(45). In 1916, Lewisohn et al reported that - in vitro - 0.1% concentration of sodium citrate in blood did not delay clotting,  but 0.15% allowed fluidicity for two days. Non-animal research suggested a concentration of 5gm of sodum citrate in transfused blood(46).

In 1916, two members of the Bureau of Chemistry at the US Department of Agriculture conducted tests in animals to try and assess the toxicity of sodium citrate - and found that administered intraveneously, the fatal dose could be as low as 0.4gms per kg body weight of the animal(47). Extrapolated to a 70kg human patient, the results of animal tests would mean that a dose of 2.8gms would be fatal, whereas in vitro findings had shown a suggested dose of 5gms.

Use during World War I (1914-18) showed that citrated blood was safe in humans - but this not stop later animal experiments adding to confusion.

In 1943, experimenters warned - from the results of experiments in dogs repeatedly bled and transfused with their own blood mixed with citrate - the dangers of transfusing large amounts of citrated blood(48) - but within months, the experimenters were proved to be wrong - when doctors transfused up to 6000ml of citrated plasma into 53 patients from two to six hours - with no adverse reactions(49).

refs

1. Maluf,NSR. J of History of Medicine. vol IX. 1954. 

2. Libravius,A. Appendix necessaria syntagmatis chymicorum. Hoffman.1615.

3. Folli,F. Sandera medica... 1680.

4. Maluf,NSR. J of History of Medicine. vol IX. 1954.

5. Lower,R. Tractatus de Corde. 1669. [translation Franklin,KJ. 1932]

6. King,E. Philosophical Transactions. vol 2. 1667.

7. Denis,J-B. Philosophical Transactions. vol 2. 1667.

8. Maluf,MSR. J of History of Medicine. vol IX. 1954.

9. ibid.

10. Keynes,G. Blood Transfusion. John Wright & Sons Ltd. 1949.

11. Maluf,MSR. J of History of Medicine. vol IX. 1954.

12. ibid.

13. ibid.

14. King,E. Philosophical Transactions. vol 2. 1667.

15. Blundell,J. Medico-Chirurgical Transactions. vol 9. 1818.

16. Blundell,J. Researches physiological and pathological. E Cox & Son. 1824.

17. Blundell,J. Lancet. vol i. 1829.

18. Keynes,G. Blood Transfusion. John Wright & Sons Ltd. 1949.

19. Hewson,W. Experimental Inquiries... J Johnson. 1774.

20. Maluf,MSR. J of History of Medicine. vol IX. 1954.

21. Prevost,JL. Dumas,JBA. Ann of Chim (Phys).vol 18. 1821.

22. Maluf,MSR. J of History of Medicine.vol IX. 1954.

23. ibid.

24. Freidberg,H. Die Vergiftung mit Kohlendunst. 1866.

25. Maluf,MSR. J of History of Medicine. vol IX. 1954.

26. Keynes,G. Blood Transfusion. John Wright & Sons Ltd. 1949.

27. Gesellius,F. Die Transfusion des Brutes. vol. VIII. 1873.

28. Hasse,O. Die Lammblut-Transfusion beim Menschen. 1874.

29. Maluf,MSR. J of History of Medicine. vol IX. 1954.

30. ibid.

31. Ponflick,E. Virschows Arch. vol 62. 1875.

32. Landois,L. Die Transfusion des Brutes. vol X. 1875.

33. Maluf,MSR. J of History of Medicine. vol IX. 1954.

34. ibid.

35. Hicks,JB. British Medical Journal. 8 Aug 1868.

36. Hicks,JB. Guy`s Hospital Report. vol14. 1869.

37. Maluf,MSR. J of History of Medicine. vol IX. 1954.

38. Wright,AE. British Medical Journal. 14 Jul 1894.

39. Maluf,MSR. J of History of Medicine. vol IX. 1954.

40. ibid.

41. Landsteiner,K. Wein Klin Wschr. vol 14. 1901.

42. Keynes,G. Blood Transfusion. John Wright & Sons Ltd. 1949.

43. J of American Medical Association. vol 228. 1974.

44. Agote,L. An Inst Modelo Clin Med. vol 1. 1915.

45. Lewisohn,R. Med Rec New York. vol 87. 1915.

46. Lewisohn,R. Ann Surg. vol 64. 1916.

47. Salant,W. Wise,LE. J of Biological Chemistry. vol 28. 1916.

48. Bruneau,J. Graham,EA. Arch Surg. vol 47. 1943.

49. Allen,JG et al. Surgery. vol 15. 1944.

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