The Development of Modern Blood Transfusions

Overview

During the nineteenth century physicians began experimenting with blood transfusions, directly from donor to patient. Most failed until Karl Landsteiner (1868-1943) discovered blood groups, which must be matched properly for a successful transfusion. The development of anticoagulant drugs around 1914 allowed blood to be stored. Blood banking began in 1937, and the system was expanded greatly during World War II.

Background

In 1628 English physician William Harvey (1578-1657) described the circulation of blood in the body. This sparked interest in understanding the functions of the blood, and physicians became interested in replacing lost blood through transfusions. Soon after Harvey published his work, transfusions between animals were attempted. In 1665 another English physician, Richard Lower (1631-1691), successfully transfused blood between dogs.

Since animals could be induced to "donate" blood more readily than seventeenth-century humans, they were eyed as possible sources of blood for human patients as well. In 1667 Lower and Jean-Baptiste Denis (1643-1704) independently reported transfusions of lamb blood into humans. However, such experiments often resulted in deadly reactions, one of which led to Denis's arrest. Animal-human transfusions were soon prohibited by law.

In 1818 an Englishwoman who was hemorrhaging after childbirth was successfully treated with a blood transfusion. Using a hypodermic syringe, physician James Blundell administered about four ounces of blood that had been extracted from her husband's arm. Blundell performed 10 additional transfusions between 1825 and 1830, of which half were successful. This was the pattern for early transfusions: sometimes they helped, but sometimes the patient had a severe, often fatal reaction. In 1875 German physiologist Leonard Landois first described how incompatible transfusions resulted in the clumping and bursting of red blood cells, a process called hemolysis. It was not until the dawn of the twentieth century that Landsteiner, an Austrian-born American immunologist, discovered why this occurred.

Landsteiner discovered three different blood groups—A, B and O—in 1901. The next year, another research team added the AB group. Red blood cells of groups A and B have A or B antigens, specific sugar-containing substances, on their surfaces. AB group blood cells carry both antigens, and O blood cells have neither. Antibodies in the blood serum react to antigens of a different group and destroy the red blood cells. Landsteiner was awarded the 1930 Nobel Prize for Medicine for his work.

Together with Alexander Wiener, Landsteiner discovered another important blood type distinction, the Rh factor, in 1940. The Rh factor accounted for the majority of the remaining transfusion reactions, especially cases in which an Rhnegative mother's antibodies attack an Rh-positive fetus' red blood cells during pregnancy, resulting in hemolytic disease in the newborn. Several other blood group systems were later identified, some as the result of a rare and unexpected hemolytic reaction after a transfusion or pregnancy.

Impact

The knowledge of the different blood groups was quickly put into practical application. The blood types of donor and recipient could be checked, and blood could be cross-matched, or mixed in the laboratory, to see if dangerous clumping occurred. The ability to type and cross-match for compatibility between blood donor and recipient greatly increased the likelihood that a transfusion would be successful.

It was soon realized that type O blood, free of A or B antigens, could be given to patients of any group; people with type O blood are universal donors. Similarly, patients with type AB blood are universal recipients, since their blood will not react to either the A or B factors. In the United States, 40-60% of the population has type O blood.

In New York, Reuben Ottenberg observed the Mendelian inheritance of blood groups. A child inherits one allele for blood type from each parent. An AA or AO pattern will result in a blood type of A. Similarly, a BB or BO inheritance will produce a B blood type. A child receiving an A allele from one parent and a B from the other will have blood type AB. Only if each parent passes along an O will the child have blood type O. This is the reason blood tests have often been employed to determine whether or not a man could have fathered a particular child. For example, if the child has a blood type of O, a man with a blood type of AB could not be the father, because he could only have passed along either an A or B allele.

With blood-typing well understood, transfusions could then be performed with greater confidence, but the technique was still difficult to implement on a large scale. Since blood clots so quickly, a donor of the right blood type had to be present on the spot to provide blood for a patient. In 1915 Richard Lewinsohn at New York's Mount Sinai Hospital used an anticoagulant, sodium citrate, to prevent donated blood from clotting. This allowed blood to be collected from the donor into a container and transported to the recipient, rather than requiring vein-to-vein transfusion. The next year, Francis Rous (1879-1970) and J. R. Turner introduced a citrate-glucose anticoagulant, allowing blood to be stored in refrigerated containers for several days. For the first time, "blood depots" could be set up, as was done by Oswald Robertson for the British military during World War I.

In the Soviet Union, thousands of quarts of blood were being collected, stored, and shipped around the country by the 1930s. However, lack of care in monitoring storage times coupled with insufficient attention to cleanliness led to a reaction rate of more than 50%. This made American physicians cautious about blood storage. American physician Bernard Fantus established the first blood bank in the United States at the Cook County Hospital in Chicago in 1937. He collected blood from donors in flasks containing sodium citrate, tested, sealed, and refrigerated it. His patients' reaction rate was far lower than experienced in Russia, and this encouraged wider use of blood transfusions.

During World War II, Charles R. Drew (1904-1950) launched a large-scale blood drive called "Plasma for Britain" involving the American Red Cross. Drew's contributions also included advocating the use of a blood component called plasma. Plasma contains important fractions of blood such as albumin to augment blood volume, fibrinogen to enable clotting and wound healing, and gamma globulin to fight infection. At the time, it could be stored longer than whole blood, making it very useful for emergency transfusions on the battlefield and elsewhere. However, it was prone to contamination, and Drew developed many strict quality control procedures to ensure its safe handling. Today, most blood donations are stored as components, including plasma or its individual fractions, platelets to control bleeding, or concentrated red blood cells to correct anemia. The improved anticoagulant citrate dextrose, introduced in 1943, reduced the volume of anticoagulant that was required and allowed storage at 4°C for three weeks.

Drew, who was African-American, protested against the racial separation of stored blood, the standard procedure in the 1940s. Although physicians were well aware that there was no scientific basis for such separation, there was concern that prejudice might discourage acceptance of the valuable technique of transfusion if white patients feared receiving "black blood." The labeling of blood by race continued in the United States until the late 1960s, when it was swept away as a result of the civil rights movement.

Tragically, Drew was killed in a 1950 automobile accident in North Carolina, at the age of 45. Perhaps understandably, a myth grew up that he had bled to death because he was refused a transfusion due to his race. In fact, although the hospital he was taken to was segregated, the emergency room did serve blacks. The white doctor on duty was acquainted with Drew, worked over him for hours, and consulted specialists at the Duke University Medical Center. A transfusion was attempted, but Drew's vena cava was severed, making it impossible to stop his bleeding. His injuries, including a broken neck and a crushed chest, were simply too severe for him to survive.

During the early part of the twentieth century, the development of successful transfusions and the ability to store and transport blood made it possible to save many other victims of trauma and hemorrhage who would otherwise have died. Later innovations, such as heart-lung machines that allowed open-heart surgery, were also enabled by progress in blood transfusion.

SHERRI CHASIN CALVO