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On 15 February 2013 (2 February on the Julian Calendar) we celebrated the 100-year anniversary of the world's first successful experimental plasmapheresis. Scientific research projects in this field were carried out by the Department of Infectious Disease, Russian Imperial Medical Surgical Academy located in Saint-Petersburg. Doctor of Medical Sciences and Professor Vadim A. Yurevich was a Principal Investigator for this research, which in 1913 resulted in the discovery of a new way of treatment. The results were published in Russki Vratch (Russian Physician) Journal no. 18 (1914) – V.A. Yurevich and N.K. Rosenberg “For the Question Regarding Washing of Blood Outside of the Body and the Vitality of Red Blood Cells”. There was no terminology offered for this medical innovation at that time. Plasma removal was performed not solely, but in combination with washing of blood cells returned to the patient. Nowadays this combination is still considered to be more effective than separate plasmapheresis. According to the published experimental protocols this new treatment was done on 15 February (2 February on the Julian Calendar or “old style”). One year later in 1914 a famous researcher, John Abel and coauthors, repeated a separate plasma removal treatment with retransfusion of the blood cells and suggested the term “plasmapheresis”, which is now official. The article entitled “Plasma Removal With Return of Corpuscles (Plasmapheresis)”, written by Abel was published 3 months later than the article by Professor Yurevich. In 1924, Dr Ivan P. Mikhailovskiy repeated experiments by Yurevich and Rosenberg in vivo on a dog model, confirmed the clinical efficiency and developed the methodology in his article “Washing of Blood In Vivo, the Methodology, Problems, and Importance for the Treatment of Toxic Conditions.”
Therapeutic hemapheresis methods started to be actively used in clinical practice just 30–40 years ago. New commercial technologies available at that time allowed development of safe, secure and effective mass exchange devices and equipment for this clinical treatment. However, the theoretical and methodological basis for plasmapheresis were established at the beginning of the twentieth century.
Two scientific research centers tried to explore this problem at that time: in Russia it was in Saint-Petersburg, at the Medical Surgical Academy, Bacteriological Laboratory of Infection Diseases Department (Fig. 1), in the USA it was in Baltimore, MD, at the Pharmacological Laboratory at Johns Hopkins Medical School. Both of these centers set up the theoretical and practical basis for all modern extracorporeal blood purification methods.
Figure 1. Group of buildings for the Division of Infectious Diseases, Lebedev Street, Saint-Petersburg. (Bacteriological Laboratory was located in the 3rd building). This complex was demolished in 1985.
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John Abel's research group from Baltimore is widely known around the world. One can read a lot in almost every manual or textbook on dialysis or plasmapheresis. But the precedence of Russian scientists in this field as well as their contributions to the development of the field is much less known for unfortunate reasons.
The Russian scientific research project was lead by the head of the Infectious Diseases Division of the Medical Surgical Academy, Professor Vadim Alexandrovich Yurevich (Fig. 2).
The scientific research projects in Russia and the USA commenced operation almost at the same time in 1913–1914 and were succeeded by four papers by John Abel and coauthors (three of them in hemodialysis [1-3] and one in apheresis ) and one article from Vadim Yurevitch and Nikolay Rosenberg (Fig. 3): “For the Question Regarding Washing of Blood Outside the Body and the Vitality of Red Blood Cells” Russkiy Vratch (Russian Physician) journal no. 18 in 1914  (Fig. 4).
Figure 4. Russkiy Vratch (Russian Physician) Journal Cover Vol. XIII, no. 18, 1914 (page. 637) – First page of the article by Vadim Yurevitch and Nikolay Rosenberg “For the Question Regarding Washing of Blood Outside the Body and the Vitality of Red Blood Cells”.
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The main idea of this article was to demonstrate the possibility of active body cleaning and eliminating toxins by the extracorporeal treatment of blood. This treatment consisted of simultaneous effusion of the limited volume of blood and normal saline infusion of the same amount (volume replacement). Then blood was centrifuged at 1500–3000 rpm, plasma, platelets and leukocytes removed, and red blood cells were washed out two to three times. The original volume of the red blood cells fraction was restored with normal saline, heated up to 38–40 °C and reinfused. Furthermore, some additional treatment options for the restoration of the function of blood cells were discussed in the same article as valuable options for detoxification—for example, extracorporeal treatment of cells with oxygen.
All experimental set-ups were developed in vivo using laboratory animals (rabbits). The exact extracorporeal operation methodology had been worked out and perfected also in animals before clinical use. Sodium citrate (1.5 g in 100 mL of blood) was chosen as an anticoagulant in combination with the hemodilution procedure. The total blood volume treated by the new method was 50–75% of the total body blood amount. Total plasma volume effused was 25–35% of the total body plasma amount. Replacement was supplied by normal saline at the amount of 20%–100% in excess of the effusion volume. The detailed experimental protocols, cited in the article, demonstrate that the first successful use of the developed therapy had taken place on 2 (15) February 1913 (Fig. 5). In essence that was the first centrifuge plasmapheresis in Russia. All rabbits were alive, in good condition, showing good appetite, and there was no hyperthermia or weight loss. Most of the erythrocytes were in a good functional condition. The amount of platelets and leukocytes restored to normal levels in a short time and quite often was even higher than before the treatment. Anatomical section research showed no inner organ damage or malfunction.
Figure 5. The protocol of the first successful washing of blood experiment in a rabbit, dated February, 2nd, 1913, published in Russkiy Vratch Journal Vol. XIII, no. 18, 1914 .
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At the time, and independently from Saint-Petersburg scientists, a similar idea was suggested by Ivan P. Mikchaylovskiy, Professor of Medicine at the Kharkov University, later at the Tashkent University in Russkiy Vratch (Russian Physician) no. 25 in 1914. Later, after 10 years of systematic research, Professor Mikchaylovskiy presented his scientific results on sedimentation plasmapheresis in vivo (dog model) in Vrachebnoe Obozrenie (Physician Review) no. 5, 1924 in the paper named “In Vivo Blood Washing-out, Methodology, Problems and Importance for Organism Detoxification” .
Ivan P. Mikchailovsky was the first to successfully use the blood detoxification technology (blood washing-out) in the lethal morphine poisoning dog model: “… those animals which were underwent blood washing-out operation, in contrast with non-treated ones, didn't die from morphine, but survived the poisoning and lived their age …” As well, he demonstrated the detoxification function of the liver in an experiment of lowering the morphine concentration by the use of the dog's blood perfusion via fresh sheep liver (extracorporeal liver perfusion). His fellow, A.A. Danilov clearly demonstrated that potassium cyanide is inactivated by binding to fibrin, so based upon these data, Professor Ivan Mikhailovskiy proposed the idea that fibrinogen is a native detoxification adsorbent of blood in living organisms and that the removal of fibrinogen complexes could be effective as treatment for some poisoning. In the conclusion of that article, Professor Mikhailovskiy outlined general strategies for blood washing-out methods as a way of treatment for further development: separate washing of red blood cells, drug accumulation in erythrocytes, change of mineral or blood gas composition, enzyme enrichment, and biological blood detoxification by means of different kinds of light energy (ultraviolet or visible light).
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Analyzing the original papers, we can definitely claim Russian science precedence in this field of medicine, which was implemented by clinical practitioners from the Medical Surgical Academy. John Abel, who is officially considered to be the world's first in plasmapheresis, made corresponding references to the Vadim A. Yurevich and Nikolay K. Rosenberg paper in his article “Plasma Removal With Return of Corpuscles (Plasmapheresis)” (Fig. 6), which was published in the Journal of Pharmacology and Experimental Therapeutics no. 5 (1914). His article was submitted on 16 July 1914 and at that time he had already been informed about the Russian paper. Even now the speed of scientific information spread at the beginning of twentieth century strikes us, especially if we take into account the absence of the internet or even stable land telephone lines at that time.
Figure 6. Cover page of the Article “Plasma Removal With Return of Corpuscles (Plasmapheresis)”, published in the Journal of Pharmacology and Experimental Therapeutics no. 5, 1913–1914 (p. 25) [4, 7].
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Thus, we now can certainly say that Professor Vadim Yurevich and Dr Nikolay Rosenberg were the world pioneers of successful plasmapheresis on 2 (15 in the new calendar) February 1913 in vivo on laboratory animals (rabbits). They did that in combination with washing out the red blood cells, which is considered to be more clinically effective, according to the modern knowledge. The term “washing-out” was in use in scientific literature of that time and perhaps it reflects the essence of an experimental new way of treatment more accurately. Now we are used to using the term suggested by John Abel in 1914 – “plasmapheresis”, as he proposed this term.
Unfortunately Russian scientists were not able to continue their successful experimental research because of the 1st World War, which started in the summer of 1914, which lead the Russian Empire to the revolution of 1917. Professor and Dr Vadim Yurevich lead an interesting life with a tragic destiny; he died on 26 February 1963 far from home, and was buried at St. Vladimir's Russian Orthodox Christian Cemetery in Jackson, NJ, USA. Nikolay Konstantinovich Rosenberg chose to stay in Saint-Petersburg and became a professor of medicine. He was a 1st head of the Department of Infectious Diseases of the Medical Military Academy after the revolution (1917) and fought plenty of infectious diseases within the army and civil population of the capital. There were no further opportunities to develop his interesting method of treatment. He died in 1933 at age 57 and was buried at Bogoslovskoye cemetery in Saint-Petersburg.