If I give you four chances to travel through time, would you dare to have a blood transfusion?

Should I take this risk or that risk?

Compilation | Kestrel

Before making a medical decision, people always want to understand all the benefits and risks. But the question is, under what circumstances can we confidently say that we know enough about a drug or a treatment to use it safely?

Let's take a blood transfusion as an example. Under what circumstances would you consider a blood transfusion safe enough to consent to it?

Decision Time #1

In 1665, Richard Lower solved a fundamental problem of blood transfusion: coagulation. Once blood is exposed to air, it quickly clots and cannot be used for transfusion. Lower bled a dog so hard that it went into shock, then connected an artery from a healthy dog ​​to a vein from the dying dog using a series of catheters.

It really worked! The dog survived.

Two years later, four more blood transfusions were performed from calf and lamb arteries to human veins. The recipients suffered from a variety of diseases, ranging from persistent infections to schizophrenia.

All four patients who received xenotransfusions subsequently developed high fever, coldness, back pain, dark urine, nosebleeds, and severe burning sensations at the transfusion site. No one could find the cause of these "transfusion reactions," but all four patients survived, and some even reported relief from their symptoms.

If you were in 1667, would you choose to receive a blood transfusion?

In fact, you probably don't have that option. Because in 1667, Pope Innocent XI signed an order prohibiting Catholics from receiving blood transfusions, on the grounds that doctors who perform the operation are playing the role of God. Two years later, the French Parliament also issued a ban; eleven years later, the British Parliament followed suit. For the next two hundred years, no one dared to try this thing.

Decision Time #2

Two hundred years have passed.

After the ban gradually faded, doctors began to experiment with human-to-human transfusions. However, "transfusion reactions" have always been a problem. In 1901, Karl Landsteiner, a young researcher in Vienna, Austria, found the cause of transfusion reactions. He collected serum and red blood cells from his colleagues and found two different glycoproteins on the surface of red blood cells, named A and B. These two glycoproteins can appear alone, together, or not at all.

This resulted in four blood types: A, B, AB, and O, which had neither glycoprotein. Landsteiner discovered that serum from type A blood destroyed type B red blood cells, and vice versa. Transfusion reactions could be fatal.

Thanks to Landsteiner's discovery, the first successful human-to-human blood transfusion was performed.

In 1907, Reuben Ottenberg, a 25-year-old young doctor at Mount Sinai Hospital in New York, became the first physician to perform a human-to-human blood transfusion based on Landsteiner's work.

Karl Landsteiner won the Nobel Prize in Medicine or Physiology in 1930

If you were in 1907, would you choose to receive a blood transfusion?

Unfortunately, despite the correctness of the ABO blood type theory, there have been cases of severe transfusion reactions following blood transfusion, which means that Landsteiner's rule is incomplete.

In 1919, he discovered another protein on the surface of red blood cells, called Rh, named after the Rhesus monkey - it was in this monkey that Landsteiner discovered the Rh system.

Rh blood type is very troublesome. In particular, when a pregnant woman with Rh-negative blood is pregnant with a fetus with Rh-positive blood, it may lead to very serious consequences-neonatal hemolysis. Neonatal hemolysis usually occurs in the second pregnancy, because when the first pregnancy is delivered, the Rh-positive fetal red blood cells will pass through the damaged placental barrier into the mother's body, stimulating the mother to produce anti-Rh antibodies. In subsequent pregnancies, these anti-Rh antibodies may enter the fetus through the placenta and cause hemolytic reactions. For this reason, women with Rh-negative blood and men with Rh-positive blood were prohibited from marrying at that time. Fortunately, with this knowledge, blood matching has made transfusion reactions almost no longer occur.

Decision Time #3

By the 1930s, doctors had syringes and paraffin-coated glass tubes, which essentially eliminated the need for direct arterial-to-venous transfusions. In addition, adding 0.2% sodium citrate to the blood prevented clotting, which could be used to store the blood. With the advent of blood banks, transfusions became more common.

If you were in 1930, would you choose to receive a blood transfusion?

Around this time, people realized that the risks of blood transfusions went far beyond transfusion reactions. In the late 1930s, people had already discovered that infectious diseases such as measles, malaria, and syphilis were associated with blood transfusions, and some of the infections caused by blood transfusions were even life-threatening. In the early 1940s, a wave of infectious diseases spread through blood transfusions caused a large number of deaths, which dwarfed the number of deaths caused by transfusion reactions.

In March 1942, the U.S. Army Surgeon General noted that the incidence of jaundice (yellowing of the skin caused by liver disease) was increasing among U.S. Army personnel. Upon investigation, it was found that these patients had recently received a yellow fever vaccine stabilized with human serum. The source of the serum was nurses, medical students, and interns at Johns Hopkins Hospital in Baltimore, several of whom had a history of jaundice, and one of them was sick during the donation.

When the dust settled, more than 330,000 soldiers were infected and more than a thousand died of hepatitis.

This is the largest outbreak of an infectious disease from a single source in recorded history and highlights the dangers of disease transmission through blood and blood products.

Decision Time #4

The cause of the 1942 hepatitis outbreak was not identified until 1964. Baruch Blumberg discovered that the culprit was the hepatitis B virus. By 1971, blood tests were able to detect whether the blood contained the hepatitis B virus. In 1972, the FDA mandated that all blood must be tested for contamination with the hepatitis B virus as well as measles, malaria, and syphilis viruses.

Baruch Blumberg wins the 1976 Nobel Prize in Physiology or Medicine

Blood transfusions are now safer and easier than before.

If you were in 1980, would you choose to receive a blood transfusion?

Later, people discovered that HBV was not the only hepatitis virus that could contaminate blood products. In fact, after excluding HBV, 90% of hepatitis associated with blood transfusions was caused by hepatitis C. In the early 1980s, in less than a year, 180,000 blood recipients in the United States were infected with hepatitis C, and 1,800 of them died as a result.

Later, another virus infiltrated the blood supply system in the United States - the dreaded HIV virus. People were not only afraid of contracting HIV during blood transfusions, but also afraid of contracting it when donating blood. As of March 1983, more than 1,200 cases of AIDS had been reported in the United States, 17 of which were contracted during blood transfusions. By the end of 1983, there were more than 3,000 cases of AIDS in the United States, of which more than 1,300 people died. Between 1978 and 1985, 29,000 Americans were infected with AIDS from transfusions of contaminated blood.

Most of these patients will die from the infection. As a result, blood donations in the United States have plummeted.

To this day, one-third of Americans still believe that donating blood alone can infect someone with HIV.

Decision Time #5

In August 1984, French scientist Luc Montagnier isolated HIV. That same year, a test for HIV was developed. By April 1985, blood banks across the United States were routinely testing for HIV. At the beginning of the tragic AIDS outbreak, regulators also revised the requirements for blood handling and processing. Today, blood handling regulations for temperature, solvents, and detergents have greatly reduced the possibility of blood being contaminated by certain viruses. Since 1985, there have been no cases of hepatitis B, hepatitis C, or AIDS from the use of blood products in the United States.

Luc Montagnier wins the 2008 Nobel Prize in Physiology or Medicine | By Prolineserver (talk) - Own work, GFDL 1.2, https://commons.wikimedia.org/w/index.php?curid=5575822

If it were you, would you choose to receive a blood transfusion right now?

Whole blood samples are now routinely tested for not only hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), but also for Treponema pallidum, West Nile virus, and Zika virus contamination. All of these measures can reduce the possibility of infection, but they cannot completely eliminate it.

Pathogens not covered by existing testing may still be present in blood products. For various reasons, prions (causing mad cow disease), Epstein-Barr virus (causing mononucleosis), cytomegalovirus, parvovirus B19 (causing rash, high fever, anemia), Ebola virus, dengue virus, chikungunya virus, and several coronaviruses such as SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have not yet become the subject of routine testing.

Now, every 3 seconds, someone in the world receives a blood transfusion from a stranger. In the United States alone, 16 million units of blood (taking red blood cell transfusion as an example, 1 unit of red blood cell suspension is extracted from 400 mL of plasma (200 mL in China)) are transfused into 10 million patients each year. For those who need blood, blood transfusions definitely have more benefits than disadvantages. In my new book, "Gambling on Life: From Blood Transfusion to Mass Vaccination - A Long and Risky History of Medical Innovation", I talked in detail about how, like other therapies, on the road to safe and effective blood transfusions, some patients inevitably died.

You may think, wouldn’t there be no risk if you don’t get a blood transfusion?

But in reality, it is impossible to completely avoid risks. The only choice you have is: take this risk or take that risk.

Compiled with permission from:

https://www.the-scientist.com/reading-frames/opinion-what-the-history-of-blood-transfusion-reveals-about-risk-69105

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