History of transfusion and autotransfusion

L.TEFA[1], Ε. ARNAOUTOGLOU[1], G. DROSOS[2], T. XENAKIS[3], G. PAPADOPOULOS[1]
[1]Anesthesiology and Postoperative Intensive Care Clinic
[2]Cardiac Surgery Clinic
[3]Orthopaedic Surgery ClinicMailing address:

ABSTRACT
The development of blood transfusion, the discovery of blood types and of anticoagulant agents for its storage is described. In parallel, the development of autologous transfusion is presented.

Key words: History, transfusion, blood.

INTRODUCTION
The relationship between life and blood has been puzzling humanity since the old days, as it is shown in New Testament as well. Since ancient times there have already been many references with mythological character.
According to mythology, Medea made Jason’s father, Aesona, revive, by cutting a vein from his neck, so the old blood would go away and she replaced it with juice form herbs and birds’ entrails, so his body and mind would become younger.
Also it was believed that someone who was weak could gain strength by having a bath with blood or drinking blood from someone who was stronger. Plenius and Celcius refer to the Romans’ custom to drink fencers’ blood in the arena[10,23].
On the other hand, ancient Egyptians probably knew about blood transfusion. In ancient Egyptian papyri the practice of transfusion is referred, which is confirmed in Erophillus’s anatomy monograph[10,23].
The anatomical knowledge of ancient Greeks for blood circulation was very limited. They believed that blood was just flowing through peripheral veins and an amount of blood was running through the pores of interventricular septum to mix with the "spirit" and enriched with air to supply the brain[14]. Galenus, a Greek doctor, believed that the basic elements phlegm, blood, yellow and black gall were responsible for health and disease. These opinions had an obvious effect on medicine’s principles for almost 20 centuries. So, in case of severe disease exsanguination was applied for removing bad blood, as recommended by Galenus. There is evidence that George Washington’s death was due to hemorrhage which was induced by the doctors for therapeutic reasons.[23]

THE FIRST TRANSFUSIONS
The experiments for blood transfusion took place in sequential steps. Initially with transfusions from one animal to another and then with transfusions from animal to human.[14] The first transfusion from human to human is reported that it was held to Pontiff Inocentius VIIΙ in 149223. It is reported that he was transfused with blood from 3 boys, whose lives were sacrificed to no avail. According to Pasquale Villari’s testimony, Pontiff had a stroke and he was in such deep coma, that sometimes it was thought that he was dead. A Jewish doctor with the help of a device which had been tested only on animals, transfused Pontiff’s blood directly into a boy’s veins, while the boy’s blood was being transfused to the Pontiff. For direct transfusion thin tubes made of silk were used[23]. The experiment was repeated three times and although the lives of the three young boys were lost it had no result for the Pontiff’s salvation. It is speculated that the 3 boys lost their lives not only as a result of the transfusion, but also as a result of venous air emboli during the vein puncture. Jewish doctor’s fate who was in charge is unknown.
The announcement by William Harvey, who describes the blood circulation in a monograph with title «Exercitatio anatomica de moto cordis et sanguinis in animalibus» is an important milestone in the history of transfusion[14,23]. William Harvey himself had infused water in the circulation of a dead man, but there is no evidence that he thought about the possibility of blood transfusion.
The first man who performed a transfusion from animal to animal successfully was Richard Lower[14]. These experiments were contacted on dogs in 1665 in Oxford, while the next two years transfusions from animal to human were performed. At the same time (1667), Jean-Baptiste Denis in Paris, reported successful transfusions from sheep to human. Dennis was a theologian and he studied medicine at Montpellier. His first patient was Arthur Coga, a student at the University of Cambridge, who had been injured on his head and Dennis transfused him blood from a sheep on 23rd of November. The patient presented a persisting fever and confusion and for that reason he had undergone "20 therapeutic exsanguinations". The patient survived after a second transfusion as well on 12th of December and finally he recovered completely. Dennis in an article who published reports that the indication for the transfusion was not blood loss, but " mental symptoms" . He believed, influenced by Galenus theory, that the transfusion from a quiet animal to a worried and suffering soul could have a calm effect. However, other patients were not so lucky, as a result transfusion to be in disfavor and no other progress be made in the following years. It is referred that the first reaction to transfusion is the case of Antoine Manroy, a 34 year old man, who died and Denis was accused for this[14.23].
At the same time parallel tries were made in Germany, when J.D. Mayor performed his first transfusion to his teacher, Jochan Michaelis, professor in Medical School at the University of Leibzig, who suffered from paralysis[23].
In 1678, Paris Medical Association banned officially transfusions from animal to human, because of adverse reactions, many of which caused death[14].
In spite of all that, some years later, in 1714, Nuck, in his book «Operations et Experinenta Chirurgica», refers to the importance of transfusions and states that they should not be banned, because they are useful in heavy hemorrhages[14]. Doen reports that 6 out of 9 transfusions that he performed were successful. For the transfusions he was using syringe by bronze. One could wonder how transfusions were performed without the appropriate information about the ABO blood group system. Off-hand calculations show that 64% could be compatible, and so Doen’s results are confirmed[23].
The first transfusion from a human to another aiming at resuscitation was performed in 1818 by James Blundell1. Blundell was a gynecologist at the Guy’s and St. Thomas Hospital in London. By his experiments on dogs with hypovolemic shock he found that death from this cause could be avoided with blood transfusion from dogs. The results were not the same when human blood was infused to dogs. He found, also, that venous blood had the same efficiency with arterial in animals’ resuscitation. He concluded that only human blood should be administered to humans and this way he managed successfully women who had postpartum hemorrhage. In 1840, Blundell and Lane present the first successful whole blood transfusion for hemophilia therapy[14].

THE DISCOVERY OF BLOOD TYPES
It is remarkable that blood transfusion was successful, even though blood types were unknown. There had already been references by Landois (1875) that mixing blood cells from one animal with blood serum from other species could lead to lysis in two minutes. Being aware of past references, Karl Landsteiner from Vienna performed some experiments and proved that a person’s serum could be agglutinated with the red cells of another. He published his results in 1901, believing that it is about a phenomenon with immunologic cause and he announced that there are 3 blood groups A, B, C or Ο[17]. One year later the fourth blood group was discovered, blood group AB, by De Castello and Sturli7.
However, the first one who refers to the need for crossmatching and the definition of blood type was Ludwig Hectoen from Chicago(1907)[23]. The same year, Ottenberg describes that blood groups are inherited by Mendel’s laws and he recognizes that blood group O is the universal donor. The first one was not widely accepted, till the description of blood groups inheritance by Bernstein in 1924[19].
The relative blood group distribution among races was studied by two German researchers during the first World War[13]. Unfortunately, these evidence was counterfeited during Nazism in Germany and used for racist purposes. So, blood group B was attributed to Slavic and Jewish race, while blood group Α to persons of "arian" race. Positive characteristics, like intelligence etc to these persons. This theory was accepted during World War II and German army accepted blood only from ascertained donors from "arian" race. In parallel, USA Red Cross was gathering blood only from the same race, however it had been accepted that donors’ blood from black race could be used for albumin production. The blood segregation according to the race continued to be in due in some states of America till the end of 1960. By the end of 1950 a law passed in Louisiana which forbade doctors to administer blood from a black donor to a white patient without his consent[18].
The first evidence for Rhesus antibodies was given by Levine, Landsteiner’s student, but without being given a name to the new system[16]. The name Rhesus positive is attributed to Landsteiner and Wiener (1940), who conducted experiments on animals following Levine’s observations[16]. Other studies followed which led to the discovery of new antigens, besides others, and to the discovery of Coombs test (1945)[4].
Kell system was recognized by Coombs himself, in 1946, after the case of a newborn with hemolytic syndrome, which could not be explained with Rhesus compatibility between the mother and the child[5].

THE NEED FOR AN ANTICOAGULANT FACTOR
In 19th century it had already been obvious that for fresh blood transfusion the natural obstacle of quick coagulation should be overcome. For this reason a surgical technique was developed by Alexis Carrel, a French angiosurgeon, which allowed the transfusion of large amount of blood. This was based on the temporary anastomosis of a donor’s artery with an acceptor’s vein[3]. So, in March 1908 he used this technique to transfuse blood to a newborn girl with her father’s blood. For this purpose, he anastomosed the father’s left radial artery with the newborn’s leg vein, whose condition was deteriorating dramatically. After the transfusion the pale and motionless newborn, started crying and gained normal color[3]. In recognition to Carrel’s work, Nobel Prize for Medicine was attributed to him in 1912 and this technique was widely accepted by the surgeons of those days.
Very soon though the need for a stable, but non toxic , anticoagulant was conceived which added to the collected blood would allow its long term storage. Already in 1868, Braxton Hicks, an English Obstetrician, had used a phosphorus sodium solution, which proved to be toxic[12]. Some years later, in 1915, Richard Lewinsohn introduced as an anticoagulant factor the sodium citrate in 1% solution[20]. Initially, sodium citrate was not used for long term storage of collected blood. Experimental studies on animals by Rous and Turner, in 1916, showed that with the addition of glucose in sodium citrate solution blood could be stored for two weeks[27]. In 1955 Lewinsohn was honored with Landsteiner prize of the American organization of blood banks for the use of the first sodium citrate solution. In 1961, after many clinical trials, CPD solution ( citrate-phosphate-dextrose) is consolidated as an anticoagulant by Gibson for blood preservation up to 28 days[23]. In 1967, the role of DPG was discovered (diphosphoglycerase) by Chantin, Curnish and Benesches, whilst with Nakaos’s work it seems that the addition of adenine alters the conservation of ATP[23]. By 1950 the discovery of plastic content had already been preceded by Carl Walter[14,23].
However, the problems continued to exist. There were referred fever reactions by 10% percent of patients who received transfusions. The problem was solved by Florence Seiber, who discovered the amount of bacteria in μg which were left after sterilization, and which today we call endotoxins and are in the majority Gram negative bacilli[23]. For this discovery she was honored by the American organization of blood banks of John Elliott Memorial in 1962.
And while the first world congress for blood transfusion had already taken place in Rome in 1935, wars were a good motive for the developments of blood transfusion. It had been preceded the discovery by Edwin Cohn of the method of plasma proteins fractionation, which is still in use today. So, human albumin and plasma were the main saving fluids which were used for the management of shock in World War II.
An important milestone in the history of transfusion is the use of erythropoietin, as well as the autologous transfusion and the introduction of autotransfusion’s devices intraoperatively.

THE HISTORY OF AUTOTRANSFUSION
The first tries of autologous transfusion with reinfusion of washed blood are performed with the purpose of surgical and obstetrical patients’ resuscitation. The first reference of blood saving is indexed in the American bibliography in 1917[21]. Till the year 1936, 277 cases of autologous transfusions had been presented in bibliography[6,9,11,26]. From 1931 till the beginning of 1970, there have been published sporadic references for the use of technique on patients with hemothorax[2]. However, this technique was used only as a saving measure for a patient’s life therefore, little was known about the quality of the product which was being reinfused. In 1966 Symbas having considered a series of laboratory and clinical studies compiled an autotransfusion protocol with non elaborated blood for the therapy of patients with acute hemothorax and it was applied to more than 400 patients between 1966 and 1978[25].
The first reports regarding to the production of devices for intraoperative collection and autologous blood retransfusion were presented in 1966[8]. In 1969, the researchers referred to the use of a centrifuge device with continuous flow which had the potential to separate and concentrate red blood cells and which applied to operations of transurethral prostatectomy[28]. The first commercially available autotransfusion device was made in Bentley laboratories and consisted of one use blood collection device and a De Bakey type non shygmic pump. The first clinical trials were contacted in Vietnam and were announced in 1970[15]. The first article relating to anesthesiology appeared in 1975 with a detailed description of the experience on 71 patients, who received a mean volume of 4000 ml autotransfused blood[24]. A systemic anticoagulant therapy was not used, but the reservoir was full of crystalloids which contained 3 IU heparin/ml. According to the writers, the device was safe and efficient for patients with blind and perforans thoracic and abdominal trauma, ruptured ectopic pregnancy, as well as for patients who were subjected to many elective and emergency intrabdominal operations. Although the device was equipped with air detection system, air embolus was reported as a result of wrong handling and withdrew from the market.
The great progress was made in 1974 when Haemonetics Corporation introduced Cell Saver, a system which washes and concentrates red blood cells before their administration. Two years later, the experience with this device is announced[22]. Since then a great number of devices for intraoperative and post operative autologous transfusion has been released for clinical practice.

REFERENCES
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