George Washington Crile performed the first artery-to-vein blood transfusion and developed a device that established the technique as a practical surgical procedure.

It is impossible to say when and where the idea of blood transfusion first originated, although descriptions of this procedure are found in ancient Egyptian and Greek writings. The earliest documented case of a blood transfusion is that of Pope Innocent VII in April, 1492. The pope, who was gravely ill, received transfusions of the blood of three young boys. As a result, all three boys died, and the procedure did not bring any relief to the pope. Evidence from the centuries that followed includes occasional descriptions of blood transfusions, but it was not until the middle of the seventeenth century that the idea of transfusion gained popularity following William Harvey’s publication of his discovery of the circulation of the blood in 1628. In the medical thought of those times, blood transfusion was considered to have a nourishing effect on the recipient. In many early experiments, the human recipient received animal blood, usually from a lamb or a calf. Blood transfusion was tried as a cure for many different diseases, mainly those that caused hemorrhages, but also other medical problems and even marital problems. Medicine;blood transfusion
Blood transfusion
[kw]Crile Performs the First Direct Blood Transfusion (Dec., 1905)
[kw]First Direct Blood Transfusion, Crile Performs the (Dec., 1905)
[kw]Blood Transfusion, Crile Performs the First Direct (Dec., 1905)
[kw]Transfusion, Crile Performs the First Direct Blood (Dec., 1905)
Medicine;blood transfusion
Blood transfusion
[g]United States;Dec., 1905: Crile Performs the First Direct Blood Transfusion[01430]
[c]Health and medicine;Dec., 1905: Crile Performs the First Direct Blood Transfusion[01430]
[c]Science and technology;Dec., 1905: Crile Performs the First Direct Blood Transfusion[01430]
Crile, George Washington
Carrel, Alexis
Mixter, Samuel Jason

Blood transfusions were dangerous procedures, causing many deaths of both donor and recipient as a result of excessive blood loss, infection, passage of blood clots into the circulation of the recipients, passage of air into the blood vessels (air embolism), and transfusion reaction as a result of incompatible blood types. In the mid-nineteenth century, blood transfusions from animals to humans stopped after scientists discovered that the serum of one species agglutinates and dissolves the blood cells of other species. A sharp drop in the use of blood transfusion came with the introduction of physiologic salt solution in 1875. Salt solution was simple to use and safer than blood.

In 1898, when George Washington Crile began his work on blood transfusions, the major obstacle he faced was the problem of blood clotting during transfusions. He realized that salt solutions were not helpful in severe cases of blood loss, when there is a need to restore the patient to consciousness, steady the heart action, and raise the blood pressure. At that time, he was experimenting with indirect blood transfusions by drawing the blood of the donor into a vessel and then transferring it into the recipient’s vein by tube, funnel, and cannula, the same technique used in infusion of saline solution. The solution to the problem of blood clotting came in 1902 when French surgeon Alexis Carrel developed the technique of surgically joining severed blood vessels (anastomosis). Vascular surgery Crile learned this technique from Carrel and used it to anastomose the peripheral artery in the donor to a peripheral vein of the recipient. Because the transfused blood remained in contact with the inner lining of the vessels, blood clotting did not occur.

Crile thought that blood transfusion would be an effective method of treating hemorrhage and shock, unlike the infusion of saline solution. He started experimenting with blood transfusions on dogs in the Laboratory of Surgical Research of Western Reserve University in 1904, and he performed the first direct human blood transfusion in December, 1905. The patient, a thirty-five-year-old woman, was transfused by her husband but died a few hours after the procedure. In his autobiography, Crile wrote, “This was the first case in which . . . a transfusion of blood by direct anastomosis of the vascular system of one human being to another was ever attempted.”

The second transfusion, and the first successful one, was performed on August 8, 1906. The patient, a twenty-three-year-old male, suffered from severe hemorrhage following surgery to remove kidney stones. After all attempts to stop the bleeding were exhausted with no results and the patient was dangerously weak, transfusion was considered as a last resort. One of the patient’s brothers was the donor. Following the transfusion, the patient showed remarkable recovery and was strong enough to withstand surgery to excise the kidney and stop the bleeding. When his condition deteriorated a few days later, another transfusion was done. This time, too, he showed remarkable improvement, which continued until his complete recovery.

For his first transfusions, Crile used the Carrel suture method, which required using very fine needles and thread. It was a delicate and time-consuming procedure. At the suggestion of surgeon Samuel Jason Mixter, Crile developed a new method using a short tubal device with an attached handle to connect the blood vessels. He called this the “cannula method of blood-vessel anastomosis.” In this method, 3 to 4 centimeters (a little more than an inch) of the vessels to be connected are surgically exposed, clamped, and cut, just as was done under the previous method. Instead of the blood vessels’ being sutured, however, the recipient’s vein is passed through the tube and then cuffed back over the tube and tied to it. The donor’s artery is then slipped over the cuff. The clamps are opened, and blood is allowed to flow from the donor to the recipient. In order to accommodate different-sized blood vessels, Crile had tubes of four different sizes made, ranging in diameter from 1.5 to 3 millimeters (0.06 to 0.12 inch).

Still, even after Crile’s method was accepted, blood transfusion continued to be a procedure performed only by a surgeon in an operating room. It required a full operating room staff, with two assistants, three nurses, and an orderly. Both donor and recipient were sedated with morphine, and local anesthesia was applied to the surgery site. Although some of the risks of earlier transfusions were greatly reduced as a result of surgical and sterile technique, blood transfusion was neither a safe nor a simple procedure.

In 1900, Karl Landsteiner Landsteiner, Karl first reported the discovery of three different blood groups—A, B, and C (later renamed O)—and the agglutinating effect that occurs when incompatible blood groups Blood groups are mixed. It took eleven years before cross-agglutination was first used as a test before blood transfusion. Crile did not apply this test to his transfusion subjects; therefore, transfusion reaction, sometimes fatal, continued to be a serious risk. Although Crile made some use of laboratory tests before transfusion, he did not consider them reliable. He wrote, “In the interpretation of results and their clinical application, experience has shown that the occurrence of hemolysis in vitro before transfusion does not necessarily indicate that it will occur in the vascular system of the recipient after transfusion.” This conclusion, published in Crile’s most authoritative book on transfusion, led many physicians to overlook the importance of compatibility tests before transfusion.

Direct blood transfusion had two additional disadvantages: First, Crile’s method did not allow for an accurate measurement of the amount of blood transfused, thus both recipient and donor were at risk; and second, it necessitated the sacrifice of the donor’s artery.

Crile’s method was the preferred method of blood transfusion for a number of years. Following the publication of his book on transfusion, several modifications to the original method were published in the medical journals of the time. In 1913, Edward Lindeman Lindeman, Edward developed a method of transfusing blood by simple needle puncture, making transfusion for the first time a nonoperative procedure. This method allowed medical personnel to measure the exact quantity of blood transfused. It also allowed a donor to serve in multiple transfusions. This development opened the field of transfusions to all physicians, and the elimination of the need to sacrifice an artery in the process of transfusion rapidly increased the number of willing donors. Lindeman’s needle-and-syringe method also eliminated another major drawback of direct blood transfusion: the need for donor and recipient to be in close proximity.

In April, 1915, American surgeon Richard Lewisohn Lewisohn, Richard developed the citrate transfusion, Citrate blood transfusion later known as Lewisohn’s method. Lewisohn showed that mixing low doses of citrate solution with blood could prevent the blood from clotting without making it toxic for the recipient. This development made indirect blood transfusions a practical method. During World War I, the citrate method became the standardized practice in the treatment of military personnel. Blood transfusions were applied for the first time by a large, specially trained transfusion team, with the result that the lives of many wounded soldiers were saved.

In the 1940’s, the method of preserving blood with citrate was refined and modified. Acid citrate dextrose was developed, which made possible the preservation of red cells in whole blood for up to twenty-one days. This development made practical the collection, storage, and distribution of blood. It enabled transfusion medicine to fulfill its lifesaving potential. Because the importance of blood group compatibility had been scientifically established, and given that quick and reliable tests for blood type had been developed, transfusion was considered for a long period to be almost free of risk to the patient. As a result, transfusion practice grew rapidly. For the health care system to be able to realize fully the benefits of transfusion, it was necessary to arrange for a supply of donor blood that would be available at all times. This need gave the push to the establishment of blood banks, in which large quantities of blood are stored in refrigerators.

Among the major developments that occurred in transfusion medicine following World War II were methods for separating and preserving the formed elements of blood—methods for freezing, thawing, and washing blood cells. These developments enabled the use of transfusions to support patients undergoing more aggressive therapy.

In the 1980’s, transfusion medicine faced its most serious challenge since the days of Crile with the discovery that the human immunodeficiency virus (HIV) can be transmitted by blood. Major efforts were undertaken to make blood transfusion a safe mode of therapy once again. Medicine;blood transfusion
Blood transfusion

• Bernheim, Bertram M. Adventure in Blood Transfusion. New York: Smith & Durrell, 1942. A fascinating book about the personal experience of Bernheim, a professor of surgery at The Johns Hopkins Medical School, with blood transfusion. Bernheim was the first to apply and modify the Crile method at his hospital in 1909. Illustrated.
• Crile, George Washington. “Direct Transfusion of Blood in the Treatment of Hemorrhage.” Journal of the American Medical Association 47 (November, 1906): 1482-1484. A short but very influential article in the modern history of blood transfusion. This and “The Technique of Direct Transfusion of Blood” are the first published reports of Crile’s experiments with animals and his clinical cases. They contain the first detailed descriptions of the Crile method of direct blood transfusion and the patients Crile treated.
• _______. George Crile, an Autobiography. Edited by Grace Crile. Philadelphia: J. B. Lippincott, 1947. This book, edited by Crile’s daughter, is recommended for those interested in the life of George Crile, one of the most prominent American surgeons at the beginning of the twentieth century. Among Crile’s many other achievements, it discusses the first direct blood transfusion. Illustrated and indexed.
• _______. Hemorrhage and Transfusion: An Experimental and Clinical Research. New York: D. Appleton, 1909. This book is divided into two major parts: The first is an examination of the problem of hemorrhages, and the second is dedicated to a detailed study of blood transfusions. Provides a thorough examination of the different aspects of blood transfusion, stressing the pioneering stage at which this technique stood in 1909. Includes many descriptions of experiments with dogs in addition to exact explanations of the two major techniques of direct blood transfusion. Illustrated.
• _______. “The Technique of Direct Transfusion of Blood.” Annals of Surgery 46 (September, 1907): 329-332. This and “Direct Transfusion of Blood in the Treatment of Hemorrhage” contain the first detailed descriptions of the Crile method of direct blood transfusion and the patients Crile treated.
• Maluf, N. S. R. “History of Blood Transfusion.” Journal of the History of Medicine 9 (January, 1954): 59-107. This is one of the best articles on the history of blood transfusion from ancient history up to the early decades of the twentieth century. Provides detailed description of the different and changing applications of blood transfusions as well as the techniques and tools used. Includes many excellent illustrations and an extensive bibliography.
• Starr, Douglas P. Blood: An Epic History of Medicine and Commerce. New York: Alfred A. Knopf, 1998. A study of the role blood has played throughout human history. The chapter titled “A Strange Agglutination” includes discussion of the discovery of blood types and the effect of that discovery on blood transfusions.

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