“If you prick me do I not bleed?” —Shakespeare
The notion that blood circulates and that it can be transfused was “based” on the observations of a Brit named William Harvey. In the 1600s he cut open a few living fish and snakes, and learned (and wrote) that the ancients were wrong. Blood didn’t come from the liver and slowly ebb through the body. Its flow was “propelled by the heart” and the red stuff traveled through tubes called arteries. In the 1800s a few doctors used a syringe to remove blood from one person and directly inject it into the vein of another.1 It helped some and harmed others.
Before the 20th century, doctors rarely considered transfusing people who bled profusely. Blood solidifies when it is outside the body, and when fresh blood from one person’s veins was infused into the veins of another, it often caused fever, kidney failure, and death.
In a test tube, blood separates into two components. Red stuff, cells, occupy the bottom half of the tube, and clear fluid, serum, fills the top half. In the early 1900s, a Viennese immunologist named Karl Landsteiner mixed his red cells with the serum of others and noticed that some combinations clumped and others didn’t. He wrote a paper and in a footnote suggested there probably were several “types” of blood antigens. Then he and his students spent eight years working out the details. By 1909, they knew there were two populations of antigens on the surface of red cells and two populations of antibodies in the serum. They labeled them A and B and discovered that:
When the cells have A antigens on their surface, their serum contains antibodies that break up B red cells.
When the exterior of red cells are not covered with A or B antigens, their serum has antibodies that break up both A and B red blood cells.
When red cells have both A and B antigens on their surface, their serum does not contain A or B antibodies.
During the next few years Landsteiner, a significant Austrian researcher, “discovered how to infect monkeys with the syphilis bacterium and he helped prove polio was an infectious disease,” but his blood group findings didn’t seem to have a practical application.
Karl was 6 when his father’s life ended and he was 40 when his mother died. He was so devoted to her that he “had her death mask taken” and hung it on his wall for the rest of his life. He married 8 years after her demise.
In 1914, the rulers of the great European empires declared war, and 9 million young soldiers killed one another.
In 1917, the U.S. entered the Great War and Oswald Robertson, a doctor from Fresno, California, was sent to the front. He had learned about Landsteiner’s work on blood types and knew that a series of doctors had recently discovered that when sodium citrate is added to blood it doesn’t clot. While caring for wounded troops, he collected blood in glass bottles, added sodium citrate to keep it from solidifying, and stored the liquid in ice. During the war, he transfused hundreds of wounded soldiers. Near the end of the conflict, he was teaching doctors from other units how it was done.
After the war, Robertson became a pneumonia researcher in New York. In 1923, he helped develop a school of medicine in China. While there, he developed a bad case of typhus, and when he recovered he returned to the U.S. He continued to be a researcher for most of his life, but he apparently was never again interested in blood or transfusions. He spent the last years of his life working in a laboratory in California’s Santa Cruz Mountains where he studied the death of Pacific salmon.
During the two decades that followed the Great War, there were no blood banks and probably not many transfusions.
When the war ended Karl Landsteiner was living in Vienna. It had been the capital of the vast Austro-Hungarian Empire and was on the losing side of the First World War. The imperial lands were carved into many of the nations of modern-day Europe and there were shortages. That winter, Landsteiner’s laboratory wasn’t heated and a group of poor people “cut down the trees around his house for firewood and tore away his fences.” Feeling personally threatened, Landsteiner moved to Holland with his wife and children. During the next three years, he performed experiments and was assisted by a manservant and a nun who was “very devout and frequently quit the lab for prayers or to serve as an organist in the chapel.” A year or so later, Landsteiner accepted a position at the Rockefeller Institute and moved his family to New York City. On the ship that crossed the Atlantic, he told another passenger how much he loved living in the “little cottage with a rose garden” in the seaside town of Scheveningen, Holland. When he got to New York, he was surrounded by a new and different environment. He lived “on the floor above a butcher shop on a street with trolley cars.” Avoiding social activities, he spent his days in the lab, and read and thought at night “until the late hour.” In 1930, he received the Nobel Prize. In 1937 Alexander Wiener added another red cell surface antigen, the RH (Rhesus factor), to his equation.
The first blood bank was set up by in Russia in 1932. Doctors at Chicago’s Cook County Hospital are given the credit for opening the first American facility that, in 1937 started to “save and store” donated blood. San Francisco’s Irwin Memorial blood bank started 3 years later.
When blood, plus a chemical that prevents clotting is put in a test tube, the cells settle to the bottom and the plasma floats to the top. For blood loss and significant anemia we transfuse packed red cells or erythrocytes. Each tiny disc lives for 120 days. In transfused blood half the red cells are new and half old, so the average cell in a unit of blood should last 60 days.
Just above the red cells in the test tube there’s a thin layer of white cells and a stratum of platelets. Each lives but a few days. Platelets are particles that plug holes and help stop bleeding. When chemotherapy suppresses the bone marrow their levels can get extremely low. In special situations blood banks have machines that dialyze off platelets, and make them available for use in another’s body. Then the platelet poor blood is infused back into the donor.
White cells are an important contributor to our defense against infection, but in transfused blood they can cause adverse reactions; as a result they aren’t collected and reused. The plasma contains proteins that, among other things, provide clotting factors.
Before blood is dripped into a body the receiving patients are screened for antibodies in their plasma/serum that might react with transfused red cells. Some of the recipient’s serum is mixed with cells that are about to be transfused. We need to make sure the cells won’t agglutinate, stick together.
In 1940, a year and a half before the U.S. became combatants in the Second World War, London was being bombarded by Nazi planes. Many in the U.S. wanted to aid the wounded, and an effort to provide the cell free portion of the blood, the plasma, to the Brits was started in New York. Called Blood for Britain, the organizers attempted to collect thousands of units of blood, separate the cells from the plasma, and under sterile conditions ship the fluid across the Atlantic. It was a huge undertaking and Charles Drew, the man in charge had previously only organized a group of people once. As a young man, he coordinated the paper routes of ten childhood friends who were delivering 2,000 newspapers a day.
Drew, was a doctor. When he was a trainee he studied the preservation of blood product, and he knew how to produce plasma that had a two month shelf life. His doctoral thesis was titled “banked blood.” Gathering, transporting and processing thousands of units of blood was a complex undertaking but he pulled it off and was able to send close to 15,000 pints of the precious fluid to the Brits. An African American, Drew was born in Washington D.C. and was an outstanding high school athlete. He was Amherst universities’ most valuable football player in 1926, went to medical school at McGill University in Canada, and graduated in 1933. In 1941 he became the director of the first U.S. Red Cross blood bank. He left after learning the organization labeled each unit of blood with the donor’s race and didn’t give the blood from a black donor to a white patient. He’s credited with saying “No official department of the Federal Government should willfully humiliate its citizens; there is no scientific basis for the practice; and people need the blood.” Drew returned to Howard University and became the chief surgeon at Freedmen’s Hospital.7
By the time I entered med school (1958) blood drives had come to my campus annually, and I had been a donor twice. The Red Cross proudly boasted that it saved the lives of wounded service men and women. People who were hemorrhaging or very anemic often needed transfusions. When I graduated in 1962 there were already 4400 hospital blood banks and 178 Red Cross and community facilities. I never knew what medicine was like before transferable blood was readily available.
In 1997 several San Francisco Bay area blood banks merged and called themselves Blood Centers of the Pacific. The non -profit corporations collected huge amounts of blood (200,000 units a year) from willing voluntary donors. They then checked it for blood type and for disease, fractionated the fluid into its various components, and sold– supplied it to more than 60 hospitals. Their annual budget exceeded $40 million.
The blood supply is relatively safe, in part because of the outrage of an angry man. In the 70s a California legislator named Paul Gann capped our property taxes. That made him famous. But the legislation that bears his name, the Gann Act, has nothing to do with property tax. It deals with transfusions. It seems that around 1982 Gann had heart surgery and was transfused. 5 years later he discovered he had HIV. The blood he received came from someone who was infected with the AIDS virus. Either the blood donor had not been adequately screened or the blood Gann received was not tested carefully enough. Gann was furious and apparently felt: “there oughta be a law.” So he wrote one.
Prior to elective surgery California doctors must tell patients that they can store their own blood and have it available should they require a transfusion. Stock piling blood prior to planned surgery can be tedious and costly. But it’s intuitively better to get your own blood back than it is to receive that of another. It’s also the law, so if the patient wants it we do it. The act also says people can refuse blood from the “bank” and, instead get it from a donor they designate. The idea makes sense, but the blood from a friend or loved one is no longer safer than banked fluid. Before it’s given all blood must be tested for the usual suspects, and it’s logistically near impossible to collect, check, and process designated blood in an acute or urgent situation.
Before Gann’s outrage some blood bank executives argued that if they looked at blood too carefully they would have to reject many donors, throw away too many units. Doctors wouldn’t be able to treat the ill. People would die. After the Gann incident blood banks (which were pretty good at questioning people about risk factors) got serious about screening blood for HIV, HTLV, Hepatitis B, Hepatitis C, (and a few other illnesses such as mosquito born West Nile virus, Zika, Cytomegalovirus, Chagas, a parasitic disease whose normal habitat is Central and parts of South America, and Babesia, a parasite that is transmitted by ticks and is found in New England.)
We’re apparently NOT yet testing the 11 million units of blood Americans use each year for: dengue, a viral disease transmitted by mosquitoes that’s common in the tropics, Chikungunya a viral illness found in Asia and Africa, that is spread by mosquitoes and was the cause, between 2014 and 2016, of fever and joint pain in 4000 American travelers, most of whom had recently visited a Caribbean island.5; we’re also not checking the blood we transfuse for Hepaitis E, the most common type of acute hepatitis in India and parts of Asia.2
Before 1996 blood banks identified viral diseases by checking for the presence or absence of specific antibodies in the serum. When a virus invades a body, the immune system reacts and makes detectable antibodies. It was believed that blood that did not contain certain antibodies should not be infectious. To prove they were right blood banks participated in studies on people who were transfused with blood whose antibody levels had been tested. 2.3 million transfusions were given during the study period and people were subsequently evaluated to see if they remained disease free. One in every 493,000 infused units caused HIV; Hepatitis C was seen after one in a hundred thousand transfusions; Hepatitis B one in 63,000, and HTLV one in 640,000 units.3 Screening was good but imperfect. During the early weeks after a person is infected, the virus incubates and its number grow. It takes a while before measurable antibodies develop. So blood can be contagious when the antibody tests are negative.
Over time PCR technology improved and we were able to directly detect and measure miniscule amounts of virus. (PCR is like a Xerox machine for DNA. It allows technicians to make millions of copies of the original, to turn a tiny amount of material into a wad large enough to analyze and learn what we are dealing with.) In 1999 blood banks started using the technique to screen all 66 million units of blood that were transfused. Between 2006 and 2008, with PCR testing being used, the recipients of 3.5 million Units of blood were checked to see if they had been infected with any of three common chronic viral diseases. One in 1.85 million units of blood that were free of “measurable” viral particles caused an HIV infection; one in 246,000 transmitted hepatitis C, and one in 410,000 gave the recipient Hepatitis B. We’re not perfect yet.4
While blood is donated freely, screening the donor, and acquiring, testing and distributing the red stuff is expensive. A recent survey put the cost of a unit of transfused blood at $522 to $1,183. In most hospitals much of the blood is used at the time of surgery. Hospitals vary in size and in the numbers and the types of operations performed. So it’s not surprising that, in the same survey, acquired blood cost $1.6 million to $6 million per hospital annually.
- http://www.animalresearch.info/en/medical-advances/timeline/blood-transfusion/
- NEJM Sept 28, 2017
- N Engl J Med June 27, 1996
- N Engl J Med January 20, 2011
- UPTODATE–Chikungunya
- https://www.nobelprize.org/prizes/medicine/1930/landsteiner/biographical/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651504/ https://en.wikipedia.org/wiki/Charles_R._Drew https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays#Multiplex%20Assays
- https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.1947.0002