Blood substitute

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A blood substitute (also called artificial blood or blood substitute ) is a substance used to mimic and satisfy some biological blood functions. It aims to provide an alternative blood transfusion, which is transferring blood or blood-based products from one person to another. So far, there is no substitute for the well-received blood of oxygen carriers, which is the typical goal of red blood cell transfusion; however, there is a large volume of non-blood volume expander for cases where volume restoration is required only. This helps doctors and surgeons avoid the risk of disease transmission and immunosuppression, overcoming the shortage of chronic blood donors, and overcomes the concerns of Jehovah's Witnesses and others who have religious objections to receiving blood transfusions.

The main categories of 'pursuing oxygen carrier' blood substitutes are oxygen-based hemoglobin (HBOC) carriers and perfluorocarbon-based oxygen carriers (PFBOCs). Therapeutic oxygen in clinical trials in the US and Europe, and Hemopure is available in South Africa.

Video Blood substitute

Histori

After William Harvey discovered the bloodline in 1616, many people tried to use liquids such as beer, urine, milk, and non-human animal blood instead of blood. Sir Christopher Wren (17th century) suggested wine and opium as a substitute for blood.

At the beginning of the 20th century, the development of modern transfusion drugs initiated through the work of Landsteiner and co-authors opens the possibility of understanding the general principle of blood type serology. Simultaneously, significant advances were made in the areas of cardiac physiology and circulation as well as in the understanding of the mechanisms of oxygen transport and tissue oxygenation.

Limitations in the treatment of applied transfusion, especially in disaster situations such as World War II, laid the groundwork for accelerated research in the field of blood substitutes. Initial efforts and optimism in developing blood substitution are very quickly confronted with significant side effects, which can not be immediately eliminated due to the level of knowledge and technology available at the time. The emergence of HIV in the 1980s renewed a push for the development of a safe blood substitute for infection. Public concern about the security of blood supply was raised further by mad cow disease. The continuous decline of blood donors combined with increased demand for blood transfusions (increased population aging, increased incidence of invasive diagnostics, chemotherapy and extensive surgical intervention, terror attacks, international military conflicts) and positive estimates of investors in biotechnology branches made for positive for further development of blood substitute.

Efforts to develop blood substitutes have been driven by a desire to replace blood transfusions in emergency situations, in places where infectious diseases are endemic and the risk of contaminated high blood products, where cooling to maintain blood may be lacking, and where possible comfortable to find blood type.

Maps Blood substitute

Approach

Efforts that focus on molecules that can carry oxygen, and most of the work is focused on recombinant hemoglobin, which usually carries oxygen, and perfluorocarbons (PFC), a chemical compound that can carry and release oxygen.

The first approved oxygen-carrying blood substitute is a perfluorocarbon-based product called Fluosol-DA-20, produced by Green Cross of Japan. It was approved by the Food and Drug Administration (FDA) in 1989. Due to limited success, the complexity of use and side effects, it was withdrawn in 1994. However, Fluosol-DA remains the only FDA-approved oxygen therapy fully approved. In 2017 no approved hemoglobin-based products are available.

By Perfluorocarbon

Perfluorochemicals are insoluble in water, so they will not mix with blood, therefore emulsions must be prepared by dispersing small droplets of PFC in water. This fluid is then mixed with antibiotics, vitamins, nutrients and salts, producing a mixture containing about 80 different components, and performing many of the vital functions of natural blood. The PFC particle is about 1/40 the size of the red blood cell diameter (RBC). This small size can activate PFC particles to traverse capillaries where no red blood cells flow. In theory this can be beneficial for damaged tissue, which is deficient in blood, which can not be reached by conventional red cells. The PFC solution can carry oxygen well so that mammals, including humans, can survive with PFC solution fluids, called respiratory fluids.

Perfluorocarbon-based blood substitutes are completely man-made; this provides more advantages than blood substitutes that depend on modified hemoglobin, such as unlimited manufacturing ability, the ability to heat sterilize, and efficient oxygen delivery of PFC and carbon dioxide removal. PFC in solution acts as an intravascular oxygen carrier to temporarily increase oxygen delivery to the tissues. PFC is removed from the bloodstream within 48 hours with a normal body cleansing procedure for particles in the blood - breathing. PFC particles in solution can carry several times more oxygen per cubic centimeter than cubic blood, while 40 to 50 times less than hemoglobin.

Fluosols are mostly made of perfluorodecalin or perfluorotributylamine suspended in the albumin emulsion. It was developed in Japan and first tested in the United States in November 1979. To "load" sufficient amounts of oxygen into it, those who have been given it must inhale pure oxygen with a mask or in a hyperbaric chamber. It was approved by the FDA in 1989, and approved in eight other countries. Its use is associated with decreased ischemic complications and with increased pulmonary edema and congestive heart failure. Due to difficulties with the storage of emulsions from the use of Fluosol (frozen storage and warming), its popularity declined and its production ended in 1994.

Oxygent is a second generation, lecithin-stabilized emulsion from PFC that is being developed by Alliance Pharmaceuticals. In 2002, phase III studies were discontinued earlier due to an increased incidence of stroke in the study arm.

Hemoglobin based on

Hemoglobin is a major component of red blood cells, which comprises about 33% of the cell mass. Hemoglobin-based products are called hemoglobin-based oxygen carriers (HBOCs).

Unmodified cell-free hemoglobin is useless as a substitute for blood because its oxygen affinity is too high for effective tissue oxygenation, the half-life in the intravascular space is too short to be clinically useful, it has a tendency to undergo dissociation in dimers with kidney damage and toxicity produced, and because free hemoglobin tends to take nitric oxide, causing vasoconstriction.

Efforts to address these toxicities include creating genetic, cross-linking, polymerization, and encapsulation versions.

HemAssist, a diaspirin cross-linked hemoglobin (DCLHb) developed by Baxter Healthcare; it's the most widely studied blood-based replacement of hemoglobin, used in more than a dozen animals and clinical studies. This achieved Phase III clinical trials, which failed due to increased mortality in the trial arm, largely due to severe vasoconstrictive complications. The results were published in 1999.

Hemolink (Hemosol, Inc., Mississauga, Canada) is a hemoglobin solution containing the o-rafinose polymerized human hemoglobin cross, which fought after the Phase II trials discontinued in 2003 due to safety concerns. It declared bankruptcy in 2005.

Hemopure is developed by Biopure Corp and hevoglobin bovin (cow) which is chemically stabilized, stable in saline solution intended for human use; the company developed the same product under the trade name Oxyglobin for the use of animals in dogs. Oxyglobin was approved in the US and Europe and was introduced to veterinary and hospital clinics in March 1998. Hemopure was approved in South Africa but the agreement was revoked and Biopure filed for bankruptcy protection in 2009. Its assets were later purchased by OPK Biotech.

PolyHeme was developed over 20 years by Northfield Laboratories and started as a military project after the Vietnam War. It is a human hemoglobin, extracted from red blood cells, then polymerized, then fed into an electrolyte solution. In April 2009, the FDA rejected Northfield's Biological License Application and in June 2009, Northfield filed for bankruptcy.

Dextran-Hemoglobin is developed by Dextro-Sang Corp. as an animal product, and is a conjugate of dextran polymer with human hemoglobin.

Hemotech is developed by HemoBiotech and is a chemically modified hemoglobin.

Somatogen develops a genetically engineered and cross-linked tetramer called Optro. Failed in phase II trials published in 2014 and development halted.

Conjugated pyridoxylated hb with polyoxyethylene was created by scientists at Ajinomoto and eventually developed by Apex Biosciences, a subsidiary of Curacyte AG; it was called "PHP" and failed in Phase III trials published in 2014, due to an increase in mortality in the control arm, leading to the closure of the Curacyte.

Similarly, Hemospan was developed by Sangart, and is a pegylated hemoglobin provided in powder form. While early trials that promised Sangart ran out of funds and closed.

Stem cells

Stem cells offer a possible way to produce transfusable blood. A study conducted by Giarratana et al. described the large-scale ex-vivo production of mature human blood cells using hematopoietic stem cells. Culture cells have the same hemoglobin and morphological content as the original red blood cells. The authors suggest that cells have a near-normal age, when compared to natural red blood cells.

Scientists from the US Department of Defense's trial arm began making artificial blood for use in remote areas and blood transfusions to wounded soldiers earlier in 2010. Blood is made up of hematopoietic stem cells removed from the umbilical cord between the mother and fetus. humans after birth using a method called blood pharming. Pharming has been used in the past in animals and plants to create medical materials in large quantities. Each cable can produce about 20 units of blood or three blood transfusions. Blood is being produced for the Agency Agency for Advanced Defense Research by Arteriocyte. The Food and Drug Administration has examined and approved the safety of this blood from previously proposed O-negative blood. Using this artificial blood will reduce the cost per unit of blood from $ 5,000 to equal or less than $ 1,000. This blood will also serve as a blood donor for all blood groups. The treated blood can be used in trials by 2013.