Blood is a miraculous and life-saving substance, yet it is not flawless. Red blood cells may typically only be preserved for up to 42 days before they should no longer be used for patient transfusions due to diminished efficacy. This brings up the first issue: shelf-life. The appropriate blood type is also a concern, which may or may not be readily available. The largest problem is, of course, the blood supply, or more specifically, whether there is any blood at all.

One in seven hospital patients requires blood, which translates to around 30,000 red cell units needed in the U.S. every day. You've probably heard blood centers all over the country talking about a "blood shortage" for months now. Finding enough volunteer donors to meet that requirement has been and continues to be a serious difficulty because it is a big order to fill. Because of this, scientists have been drooling over the prospect of producing artificial blood, or "blood replacements," for many years.


The value of a blood substitute is mostly determined by how well it distributes oxygen throughout the body, however other aspects like producibility and shelf life are also significant.


Doctors and researchers were interested in discovering a substance to replace blood lost in their patients even before actual blood transfusions were common. The National Center for Biotechnology Information (NCBI) claims that William Harvey's discovery of circulation in 1616 served as the impetus for the first attempts to discover alternatives. Medical professionals experimented with a variety of substances in the years that followed, including beer, pee, milk, plant resins, and sheep blood as a substitute for blood, according to NCBI.

In actuality, milk was well-liked. Because it was thought to enhance the generation of white blood cells, which are important for developing immunity, it was initially employed as a treatment for Asiatic cholera. In the 1870s and 1880s, cow, goat, and even human milk transfusions were particularly common in the United States, but their use soon declined as patients reported a high rate of adverse responses and other consequences.

According to NCBI, "Ringer's solution—a solution comprised of sodium, potassium, and calcium salts" was another significant invention in the 1880s. Early frog trials revealed that replacing blood with the solution might prolong the frogs' lives for a short time, which made it suitable for use in humans. Ringer's solution can still be used for this purpose today even though it is now known that it cannot replace blood due to its capacity to raise blood volume.


Simply because it had to, transfusion medicine advanced dramatically during the Second World War. Blood had to be transportable and readily available in big amounts because soldiers required it more than ever. Even though no blood replacement could be effectively developed, plasma received considerable attention during both wars since it was thought that transfusing plasma may save a soldier's life following a shock from blood loss. Scientists, for instance, created a gum-saline solution in the 1920s that prolonged plasma and allowed physicians to transfuse fewer plasma units, but it had some extremely risky health consequences and fell out of favor in the 1930s.


Unfortunately, a century later, we're still having trouble coming up with a solution. However, we do have greater knowledge, which has led to more research and studies (mostly dating back to the 1980s). According to the Pacific Heart, Lung, and Blood Institute, if a blood substitute were to be developed today, it is anticipated that it would fall into one of the following categories: hemoglobin-based oxygen carrier (HBOC) or perfluorocarbon (PFC) (PHLBI).


Hemoglobin proteins are the chemicals that enable red blood cells in the whole blood to efficiently carry oxygen. Scientists have attempted to create chemically modified [actual human] hemoglobin, which is poisonous on its own, as a blood substitute, but they have discovered that it creates methemoglobin, a byproduct that ultimately damages the body's existing cells. Modern attempts to use HBOCs center on figuring out how to encapsulate hemoglobin to convey oxygen without exposing hemoglobin or any other toxic elements to the blood directly.

One HBOC to be aware of is Hemapure, which shares many structural similarities with Oxyglobin, another HBOC that has been authorized for use in veterinary procedures since the 1990s. Hemapure is described as "purified bovine Hb [hemaglobin], chemically cross-linked for stability, and produced in a modified lactated Ringer's solution [a version of the Ringer's solution invented in the 1880s]," according to a recent publication in the Anesthesia & Analgesia journal.

The most extensively researched human blood substitute is mature. It is now authorized for "compassionate use," or circumstances where no other treatment alternatives are available, even though research on it is ongoing and it has not yet obtained full FDA approval. This is frequently the case when a patient refuses blood transfusions due to religious restrictions, when doctors are unable to locate blood that matches the patient's blood type closely enough for them to administer it safely, or in distant regions where blood cannot be quickly procured.


PHLBI states that PFCs, unlike HBOCs, are synthetic and "produced from fluorine- and carbon-containing compounds." PFCs pose a special challenge, however, in that they do not mix with blood and must be added to another solution to be effective — which can cause additional side effects/reactions, depending on what they are mixed with. PFCs are particularly useful for "dissolving and absorbing oxygen in the lungs and then transporting oxygen throughout the body." The blood replacement conundrum has been addressed by several PFCs, but none stand out as the obvious "winner."

I would suggest two main points if you wanted to remember anything from this article. First off, despite significant progress being made, the hunt for blood substitutes has been going on for hundreds of years. This brings us to the second point: Until we can develop a blood substitute, genuine, live blood donors are the only way we can satisfy patient demands.

Blood donation is a particularly special aspect of patient care because it calls for more than a care team, lab personnel, and the newest technological advancements. No matter how inventive they may be, none of those things would be of much use without the sheer, unadulterated charity of a group of individuals who genuinely want to assist. We are grateful to our blood donors for filling that role.