Blood substitutes have been required for as long as people have been bleeding to death due to a serious injury. In the years that followed, doctors experimented with a variety of substances as blood substitutes, including beer, urine, milk, plant resins, and sheep blood. One of the first of these materials was milk. To treat Asiatic cholera, patients were given milk injections in 1854. Milk injections were never popular among doctors due to their scepticism. It was tossed out after a short time. Salt or saline solutions could also be used as a replacement. It was discovered that frogs could survive for a brief period of time without blood circulation, which led to deception.

Saline was created as a plasma volume expander after a few years of research. A gum-saline solution containing galactoso-gluconic acid was utilised to prolong plasma during World War I. However, studies have revealed that chewing gum has certain harmful health impacts. During World War II, there was a renewed interest in the study of blood and blood substitutes. Human plasma was frequently utilised to replace blood and protect soldiers from haemorrhagic shock. Perfluorochemicals, a new type of blood replacement, were discovered in animal tests in 1966. (PFC). This sparked the notion of using PFC as a blood thinner.