A blood surrogate is a manufactured substance designed to fulfill a primary function of red blood cells: transporting oxygen. These products, also called artificial blood, are developed to serve as a replacement for donated blood in transfusions. Unlike donated blood, which contains components like white blood cells and platelets, a surrogate’s main goal is to replicate the oxygen-transport capacity of hemoglobin. These substances are intended to provide a bridge for oxygen delivery in the body until a patient can regenerate their own blood or receive a conventional transfusion.
The Need for Blood Alternatives
The search for a viable blood alternative is driven by the limitations of traditional blood donation. A persistent problem is the chronic shortage of donated blood, as demand often increases by 6-8% annually while donations only increase by 2-3%. This gap between supply and demand creates pressure on healthcare systems and can lead to the postponement of medical procedures.
The safety of donated blood is another concern. While screening in many developed nations has made the blood supply very safe, the risk of transmitting infections is never zero. Globally, transfusion-transmitted infections, including HIV and hepatitis, are a serious issue, particularly in regions where extensive screening is not financially feasible.
Donated blood also presents other challenges that complicate its use, especially in emergencies or remote locations.
- Immunological reactions can occur if a patient’s immune system attacks transfused cells, leading to complications from mild rashes to severe hemolytic reactions.
- It has a short shelf life, limiting how long it can be stored.
- Constant refrigeration is required for storage and transport.
- Careful blood typing and cross-matching are necessary to prevent incompatibility.
Types of Blood Surrogates
Research into blood alternatives has produced several distinct classes of products. The most studied are Hemoglobin-Based Oxygen Carriers (HBOCs). These are developed by extracting hemoglobin—the protein that carries oxygen—from sources like expired human donor blood, bovine blood, or recombinant DNA technology. This extracted hemoglobin is then purified and chemically modified to make it stable and functional outside the protective environment of a red blood cell.
Another major category consists of Perfluorocarbon (PFC) Emulsions. PFCs are entirely synthetic chemicals that have the ability to dissolve large quantities of gases, including oxygen. These manufactured liquids are emulsified—suspended as tiny droplets—in a liquid to be infused into the bloodstream. Because PFC particles are much smaller than red blood cells, they can deliver oxygen to tissues that are constricted or blocked, which normal blood cells cannot reach.
A more recent approach involves the creation of red blood cells from stem cells, sometimes called “blood pharming.” This method uses hematopoietic stem cells, the precursors to all blood cells, and cultivates them in a laboratory setting. Scientists use growth stimulants to guide these stem cells to differentiate and mature into functional red blood cells with the same hemoglobin content as native red blood cells.
Key Developmental Hurdles
The journey to create a universally approved blood surrogate has been impeded by biological and technical obstacles. A primary issue for Hemoglobin-Based Oxygen Carriers (HBOCs) has been toxicity. When hemoglobin is free in the bloodstream, it can cause vasoconstriction, a narrowing of the blood vessels. This occurs because the free hemoglobin scavenges nitric oxide, a molecule that is important for keeping blood vessels dilated, which can lead to increased blood pressure and reduced blood flow to organs.
Another challenge is engineering a surrogate with the correct oxygen affinity. The substance must be able to bind to oxygen effectively in the lungs but also release it efficiently into the body’s tissues. Unmodified hemoglobin, for example, binds to oxygen too tightly to release it where it is needed most. Modifying the molecule to achieve this precise balance of oxygen uptake and delivery has proven to be a complex biochemical problem.
Manufacturing and scalability present a major barrier to widespread use. The processes for purifying hemoglobin, synthesizing PFCs, or cultivating stem cells are technically demanding and expensive. Producing these substances on the industrial scale necessary to meet global demand would require immense investment. The short half-life of many of these products in the bloodstream, often lasting only 20-30 hours, also limits their practical application.
Current Status and Applications
Despite decades of research, no blood surrogate product is currently approved for general human use in the United States or Europe. Some products, however, have seen limited application in specific circumstances. For instance, an HBOC named Hemopure, derived from bovine hemoglobin, has been approved for use in South Africa and for veterinary purposes in the U.S. and Europe.
Ongoing research is focused on overcoming the hurdles that have limited past products. Scientists are exploring methods like encapsulating hemoglobin within artificial membranes to prevent the nitric oxide scavenging that causes vasoconstriction. The development of red blood cells from stem cells also represents a promising direction, though it is still in early clinical trial phases.
If a safe and effective surrogate can be successfully developed, the potential applications would be significant.
- Military medicine, providing immediate resuscitation for soldiers on remote battlefields.
- Civilian trauma care, especially for accident victims in rural areas far from hospitals.
- An alternative for patients who cannot receive traditional blood transfusions for religious reasons.
- A solution for patients with rare blood types or complex antibody profiles that make finding a compatible donor difficult.