TRANSFUSIONS

Blood the liquid that carries nutrition and oxygen to every corner of our body is a mixture of cells and protein rich fluid.   Most of the cells are “erythrocytes” –red cells.  As they flow through the arteries of the lung the tiny discs discard carbon dioxide and acquire oxygen.  When they are propelled through the rest of the body the cells deliver oxygen and collect carbon dioxide.

We didn’t really start to understand the value and danger of transfusing the red solution until 1900 when a Viennese Physician and researcher, Karl Landsteiner, separated blood into its two components: Cells and serum.  “Many but not all normal sera will agglutinate the red cells of other normal persons.  Human beings can be separated into groups, the bloods of those of the same group being harmless to one another8.”

A physician researcher, Landsteiner was six when his father died.  Raised by his mother Fanny, he was “so devoted to the woman that her death mask hung on his wall until he died.”  An esteemed professor, Karl was living in Vienna, the capital of the vast Austro-Hungarian Empire when the First World War ended.  His country had been on the losing side and the imperial lands were carved into many of the nations of modern day Europe.  That winter there were shortages and Landsteiner’s laboratory wasn’t heated.  One day “the Viennese poor cut down the trees around his house for firewood and tore away his fences.”  Feeling personally threatened, Landsteiner moved with his wife and children, to Holland.  During the next three years he lived and performed experiments in a “little cottage with a rose garden” in the seaside town, Scheveningen.  He was assisted by a man-servant and a nun who was “very devout and frequently quit the lab for prayers or to serve as an organist in the chapel.”  After accepting a position at the Rockefeller Institute, he moved his family to New York where 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.”  “His energy was continuous and compelling, and no moment of idleness in the lab was tolerable to him.8”   He was living in New York in 1930 when he received the Nobel Prize.6

In the early 1900s, while still in Vienna, Landsteiner identified three blood types: A, B, and O. They were based on the antigens on the surface of red blood cells,  We now, of course, know that:                                                             

  • A person with Type B blood has “B” antigens on the surface of his or her red cells. 
  • Their serum contains antibodies to blood type A. 
  • If the person is transfused with Type “A” blood, the infused red cells will agglutinate—stick to one another and form a clump.   
  • A person with Type A blood has “A” antigens on the surface of his or her red cells– and antibodies to B in their serum.  If B cells are transfused the new cells will adhere to one another.
  • People who are transfused with incompatible blood got quite ill and can die.  
  • Individuals whose red cells have both A and B surface antigens don’t have serum antibodies to either B or A.  They can receive–be safely transfused with A, B, AB OR O blood.
  • The serum of Individuals with type O blood contains B and A antibodies. They can’t safely be transfused with A or B cells, but their red cells can be instilled into people with any blood type. 
  • In 1937 Alexander Wiener added another red cell surface antigen, the RH, Rhesus factor to the equation.

During the First World War years (1914-1918) a series of doctors learned that when they added sodium citrate to blood it didn’t clot.  With additional additives it could be stored for 2 weeks. 

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.

The first blood bank was set up by the Russians in 1932. Doctors at Chicago’s Cook County Hospital are given the credit for opening the first American facility. It started to “save and store” donated blood in 1937.  San Francisco’s Irwin Memorial blood bank was established 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 or significant anemia packed red cells or erythrocytes can be transfused. 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. 

In the test tube full of blood, immediately above the red cells there’s a thin layer of white cells and a stratum of platelets.  The cells and particles only live a few days.  White cells are an important contributor to our defense against infection.  In transfused blood they can cause adverse reactions.  When chemotherapy suppresses the bone marrow white cell levels can get quite low.

Platelets are particles that plug holes and help stop bleeding. Some chemotherapy drugs can significantly suppress their blood levels for a number of days.  When the risk of bleeding is high enough platelets are collected from others and infused.   Blood banks have machines that separate and collect platelets, then reinfuse the platelet poor blood back into the donor.  

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 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. 

When he was still a trainee the doctor who was chosen to coordinate the effort, Charles Drew, studied the preservation of blood products.  He wrote a doctoral thesis titled “banked blood”, and he knew how to produce plasma that had a two month shelf life.  Gathering, transporting and processing thousands of units of blood was a complex undertaking but Drew pulled it off and was able to send close to 15,000 pints of the precious fluid to the Brits.  A black man, Drew was born in Washington D.C. and was an outstanding high school athlete. He was Amherst University’s 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. It was a big honor but he didn’t stay very long.  He resigned because 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 taxes.  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 a unit of blood is given it 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 found in New England that is transmitted by ticks.)

We’re apparently NOT yet testing the 11 million units of blood Americans use each year for dengue, a disease transmitted by mosquitoes that’s common in South East Asia— or for Chikungunya, a West Africa disease that was responsible (between 2014 and 2016) for the fever and joint pain of 4000 American travelers.  Most of them had recently visited a Caribbean island.5. And we don’t test for Hepaitis E, the most common type of 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 their blood was safe 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, and Hepatitis B one in 63,000.3 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 stuff 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. 

  1. http://www.animalresearch.info/en/medical-advances/timeline/blood-transfusion/
  1. NEJM Sept 28, 2017 
  2. N Engl J Med June 27, 1996 
  3. N Engl J Med January 20, 2011
  4. UPTODATE–Chikungunya
  5. https://www.nobelprize.org/prizes/medicine/1930/landsteiner/biographical/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651504/
  1. 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
  2. https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.1947.0002