Bloodstain Pattern Analysis devoted to the identification of biological material, DNA
interpretation and DNA statistical analysis, to detect human biologists, fingerprints , crime scene members for police record, medical examiners .
Crime scene examinations generally are associated with dwellings or structures. In reality many
crime scenes involving bloodshed may occur outside including wilderness environments. While
examination within a dwelling may take significant time to process, it will not degrade dramatically
as the surrounding structure provides protection. In contrast, the outdoor scene is subjected to the full gambit of the environmental and weather conditions.
go to Forensic
Forensic scientists may encounter blood spatter at a scene which may be pure or a mixture of fly artifacts and human bloodstains. It is important to be able to make an informed identification, or at least advanced documentation of such stains since the mechanics of production of fly artifacts are not determinable to the crime scene reconstructionist from regular police forces. We describe three cases in which experiments and crime scene reconstruction led to additional information. Case 1: Above the position of a victim, numerous blood stains of the low-high velocity type were found. Exclusion of these stains being caused by force (but instead caused by the activity of adult blow flies) by use of the following observations that were confirmed in experiments: a) Sperm-/tadpole-like structure with length > width, b) random directionality c) mixture of round symmetrical and teardrop shaped stains. Case 2: A reddish spatter field was found on a fan chain two rooms away from the place where a dead woman was found. Localization of the spatter on the bottom end of the surface hinted strongly towards fly activity. Case 3: Double homicide; submillimeter stains were found on a lamp between the two corpses. Activity of flies was less likely compared to alternative scenario of moving lampshade and violent stabbing.
Blood Stains
Initial observation of the scene gave the appearance of extensive low, medium and high velocity blood spatters. Above the position of one of the victims numerous stains of the low-high velocity type were found (fig. 1). Similar areas were found on a kitchen hanging lamp, the interior and exterior of the entry door, the bathroom, the two bedrooms and the walls around the victims. The stains were tested positive for blood with a quick test for hemoglobin (Hemastix/Heglostix)
The first assumption to be made was that there had been slinging of a lot of blood around the kitchen and living room. This would suggest not only gunshot wounds, but considerable movement of the victim and suspect(s). It could suggest a motive of robbery, burglary, assault, or a surprise attack. Examination of the kitchen and living room did neither indicate struggling or fighting to any great amount. In the bedrooms and bathroom there were flies, but no signs of bloodstain patterns. There were no maggots in these rooms. The conclusion we made was that not much activity had taken place in the bedrooms or the bathroom of an assaultive nature and the bloodshed had taken place in the kitchen and living room.
Recostructing the angle of impact of many of those stains, however, led nowhere. There was no indication that the bodies had been moved and there were no signs of a struggle in the bedrooms, or bathroom. Smaller, round type spatters were mostly < 3 mm in length and > 1 mm in diameter. Furthermore, stains of a sperm-like shape (irregular, uneven form with tail much longer than the body) as well as a missing systematic directionality were observed. Since all stains were composed of blood, how did they (a) get into all of the rooms and (b) transferred to the walls?
Conclusion
With information that stains appearing as human blood spatters were fly artifacts, coupled with other scene evidence, we felt confident that the possibility of an execution or revenge slaying could be put into the mix of suspect behaviors at our crime scene.
4. Case : Corpse of Lonely Woman
A dead female person was found in her bedroom in an urban appartment. The body had entered dried-out state of decay with severe undernourishment during lifetime and an underlying minimal greenish discoloration of the face and the abdominal area after death. In the anal region of the corpse, few blow fly maggots (oldest larval stage L3) were found. As soon as the windows were opened, adult Lucilia sp. entered the room. Therefore and because of numerous dots in the face of the dead person, the police asked if blow flies had been present, or if those dots had to be attributed to a source to be investigated on.
The windows were closed before the police entered which explained the presence of only few flies, mostly pupae of phorids (Diptera: Phoridae), was in accordance with the reconstruction of events. Apart from piles of empty pizza delivery cardboard boxes and cigarette butts, which did not provide food sources for blow flies, the appartment was very clean and expensively furnished. The bathtub was half filled with discolorated water that was most likely used to wash clothing.
Since the entrance door was regularly locked and no signs of a violent fight were present, a reddish spatter field at a fan chain in the kitchen became of interest . The kitchen was located two rooms away from the sleeping room and there was no visible evidence that linked the kitchen to any violent event. Closer examination led to the conclusion that the stains were fly artifacts. Since the eyes of the corpse were still intacts and not used as a food resource by maggots, it was concluded that only very few adult individuals of a smaller fly species had been living in the appartment at some point before, or at the time of death. Those few individuals used the fan chain as a resting place and deposited reddish material with a typical preference fort he lower border of the surface. The same effect is present under laboratory conditions, yet in a much larger scale, where the flies also preferred the bottom border of the hanging piece of paper.
Because of the nature of the stains, they were neither taken into account for the further police investigation nor the reconstruction of the events at the scene. The case was considered to be self neglect in contrast to killing, or neglect by another person.
5. Case : Slaying of mother and child
the dead bodies of a mother and her child were found in the living room of their house on the border of the city of Cologne, Germany. They had been dead for around six hours. Another child that had been sleeping upstairs was alive and not hurt. Blood stain patterns were used to determine the course of events.
The crime scene reconstruction based on blood spatter became important to check the statements of an accused man who owned a knife that was used for the stabbing. For legal technicalities (rights of inheritance) it also became important if the woman, or her child had been killed first. Thridly, the defense lawyer wanted to proof that his client had stabbed the child with brutal force to make clear that his client had no mental control in the moment he performed the stabbing. Apart from medico-legal considerations, it was thought that the velocity of the blood spatter might help to address theses questions.
Amongst numerous other reddish stains in the house (in this case, due to a local police procedure, all stains determined as originating from the victims by DNA typing), few very small stains on a lamp were observed. This lamp was located only ca. 1,80 m over ground and had been hanging directly between the locations where the two bodies were found. The police asked if these stains were caused by the impact of violence, or by flies. As in most cases, the presence of flies was not looked at by the first team which entered the house through a window. After that, all flies may have flown out of the window. Therefore, a combined blood spatter and forensic entomology expert statement was asked for by the police and later again requested by the judge during the trial.
The tiny, round stains on the lamp were distributed over the complete surface. Genetic fingerprinting led to one conclusive DNA type out of six stains (DNA of the child was found in one stain, no result in the other stains). It was discussed that the stains might have originated from the offender´s knife that got stuck in the vertebra of the child (as documented by the forensic pathologist). When the offender took the knife out of the bone with a jerk, few tiny droplets of blood may have been distributed with a relatively high initial velocity but got slowed down due to the resistance of the air.
Practical hints
From our case work experience and from our experiments, the following suggestions and techniques are offered for use in differentiating between fly artifacts and human bloodstain patterns .
1. Document fly activity at a scene. Flies will be at a scene if access to the scene is available to them. They will stay at the scene as long as a food source is available to them and/or as long as they are trapped. Therefore, check for dead flies, too. If evidence of flies is present at the scene, assume that fly artifacts will be at the scene. Follow standard protocols of description of insects at crimes scenes – where, when, how many?
2. Document the range of stains. Fly activity will often concentrate near light sources, on light colored walls, windows and mirrors. They will often be present in rooms away from the body. Compare stains away from the body with stains near the body.
3. Compare stains with known fly artifact patterns.
4. Identify suspected human bloodstain patterns that are of the "spot" or "tear" drop pattern that offer a potential for use in reconstruction and eliminate the following:
a. Stains that have a tail/body (Ltl/Lb) ratio greater than one,
b. Stains with a tadpole/sperm type structure,
c. Stains with a sperm cell type structure that do not end in a small dot,
d. Any stains without a distinguishable tail and body,
e. Any stains with a wavy and irregular linear structure,
f. Any stains that do not participate in directionality consistent with other stains that suggest a point of convergence at a point of origin. Larger fly artifacts, within a group, will point in all directions. Cast off human blood will produce stains, within a group, that indicates a common general convergence point.
5. Note the absence of known human bloodstain pattern characteristics. The absence of misting around a concentrated mass would suggest the stains might not be from human cast off blood origin. Within a group, human cast off patterns often leave secondary wave cast off patterns and run off patterns.
6. Cover blood stains, especially on the floor, with paper sheets to prevent them being destroyed by investigators walking on the stains.
7. One or two stains do not make a case. Stains that could be fly artifacts should be eliminated and an evaluation based upon stains that can be explained in terms of origin and relevance to the reconstruction.
8. Use a high resolution camera with a macro lens and include a scale in every single picture.
Forensic scientists, crime scene technicians and investigators may encounter blood spatter at a scene which may be pure or a mixture of fly artifacts and human bloodstains. It is important to be able to make an informed identification, or at least advanced documentation of such stains.
progress made synthetic blood :
You Won't Believe It's Not Blood: 5 Synthetic Substitutes for the Real ThingThe
red blood cells coursing through your veins transport the oxygen
necessary for your survival. But instead of relying on the blood bank,
researchers are now working to make their own supplies. Here are five
blood technologies in development.
The blood is created by dedifferentiating fibroblasts from an adult
donor and reprogramming them into induced pluripotent stem cells
(iPSCs), which are then cultured in a bone-marrow-like environment for a
month. Blood cells are then extracted from the cell culture. If the
technique can be scaled up to industrial levels (which is no trivial
task), beyond potentially supplying an endless supply of life-giving
blood, the artificial blood would consist entirely of young, healthy,
and infection-free cells, avoiding the issues of pathogen contamination
that have in the past plagued the donor blood supply.
“Although similar research has been conducted elsewhere, this is the first time anybody has manufactured blood to the appropriate quality and safety standards for transfusion into a human being,” Turner told The Telegraph.
The artificial blood could be transfused into patients in a clinical trial setting as early as 2016, likely for three patients suffering from a genetic disorder called thalassaemia, in which the body makes unusually low levels of hemoglobin—a problem that is treated frequent transfusions.
Correction (April 17): This story has been updated from its original version to correctly reflect that the researchers are deriving blood cells, not serum, from iPSCs, and that the cells themselves are not artificial. The Scientist regrets the errors.
Blood substitutes — also called oxygen therapeutics or hemoglobin-based oxygen carriers (HBOCs) — offer the promise of new and important life-saving medical treatments.
Blood is a vital, life-sustaining fluid that picks up oxygen in the lungs and then carries it to the heart and the rest of the body. Blood performs many functions such as transporting nutrients from the digestive system, removing toxins and waste, and fighting germs.
Blood is composed of a watery substance called plasma as well as three different types of cells or parts of cells that float in the plasma. The formed elements are red blood cells (RBCs), white blood cells (WBCs), and platelets.
White blood cells are part of the body’s immune system that destroys viruses and bacteria, the pathogens that cause infections. Platelets form clots to prevent bleeding from cuts and small wounds. RBCs account for more than 90% of the formed elements in the blood.
These abundant cells transport oxygen and carbon dioxide via blood vessels called arteries and veins. RBCs are disc-shaped with a large surface area for absorbing and releasing oxygen.
These cells do not have a nucleus in the center, but instead contain a complex molecule — hemoglobin (Hb) — that collects and releases oxygen.
With 4.5 million Americans receiving blood transfusions each year, the number of patients requiring blood is now outpacing the number of blood donors. Although the American blood supply is generally safe, small amounts of the blood stored in blood banks may be contaminated with HIV and hepatitis virus.
The need for safe artificial blood is even greater for many people outside the United States. In sub-Saharan Africa, for example, blood loss accounts for an estimated 44% of women who die in childbirth. In many countries in the Developing World, blood is not screened for infectious pathogens that cause HIV, hepatitis, and syphilis.
When blood substitutes are manufactured they can be sterilized to destroy bacteria and viruses. This eliminates the risk for infectious diseases in a blood transfusion – a major issue in many parts of sub-Saharan Africa. With a longer shelf life than human blood, some blood substitutes can be stored for one to three years without refrigeration.
Artificial blood can be safely shelved outside hospitals and then rapidly administered to patients in emergency situations. Also, patients whose religious beliefs prevent them from accepting blood from donors would benefit from blood substitutes such as PFCs that are not derived from blood products.
Over the last three decades medical scientists have made some progress in the discovery of human blood substitutes. Currently, two main types of artificial blood products — hemoglobin-based oxygen carriers (HBOCs) and perflourocarbons (PFCs) — are either being tested or are already on the market for human use.
To be effective, a blood substitute has to function like hemoglobin in carrying oxygen to organs and cells inside the patient’s body. The problem, however, is that hemoglobin outside of RBCs is toxic. Pure hemoglobin injected into the body causes blood vessels to tighten, leading to high blood pressure, capillary collapse, and sometimes heart attacks, strokes, and death.
Without its RBC wrapping, hemoglobin can produce swelling and fevers. These unwanted side effects are one of the main reasons why blood substitutes made from hemoglobin are so difficult to make.
Those receiving blood substitutes had a threefold increase in the risk of heart attacks compared with the control group given human donor blood. However, a closer analysis of the results showed that some of the negative statistics were misleading.
The artificial blood products reviewed in this study varied in their benefits and risks, and some blood substitutes had very few serious side effects. The findings suggest that some blood substitutes may be safer and more beneficial than scientists originally thought.
Perfluorocarbons (PFCs) are totally synthetic artificial blood products derived from fluorine- and carbon-containing chemicals. They are chemically inert, but more effective than water or blood plasma in dissolving and absorbing oxygen in the lungs and then transporting oxygen throughout the body. PFCs remain in the bloodstream for about 48 hours. Because of their oxygen-dissolving ability, PFCs were the first group of artificial blood products studied by scientists. They are the first generation blood substitutes. Unlike the red colored HBOCs, PFCs are usually white. However, since they do not mix with blood they must be emulsified before they can be given to patients. PFCs are such good oxygen carriers that researchers are now trying to find out it they can reduce swollen brain tissue in traumatic brain injury. PFC particles may cause flu-like symptoms in some patients when they exhale these compounds.
Examples of PFC Blood Substitutes
Fluosol-DA-20
Fluosol-DA-20, manufactured by Green Cross of Japan, was the first and only oxygen-carrying blood substitute ever to receive approval from the FDA. Although approved in 1989, it was withdrawn in 1994 because it was cumbersome to administer to patients and it had side effects.
Oxygent
Oxygent, developed by Alliance Pharmaceutical Corporation in San Diego, is a PFC-based oxygen carrier currently approved for Phase II trials in both Europe and the United States. Oxygent initially showed promise for decreasing the need for donated blood during surgery. However, phase III trials were stopped recently because patients receiving Oxygent showed a higher risk of stroke compared to controls receiving donor blood.
Perftoran
Perftoran, sponsored by Moscow, Russia, is a PFC emulsion approved for human use in Russia in 1996. In 2005, the same drug was registered and approved as an authorized blood substitute for use in Mexico under the trade name Perftec, distributed by KEM Laboratory in Mexico.
Oxycyte
Oxycyte — a third-generation perfluorocarbon (PFC) therapeutic oxygen carrier sponsored by Synthetic Blood International in Costa Mesa, California — is designed to transport oxygen to damaged tissues and carry carbon dioxide to the lungs for removal. With an oxygen-carrying capacity up to five times that of hemoglobin, Oxycyte may be beneficial for traumatic brain injury, sickle cell crisis, heart attack, and wound care as well as for blood transfusion. It has been approved for Phase II clinical trials on traumatic brain injury in Switzerland and Israel, but more research is needed before it can be deemed safe and effective as a blood substitute.
PHER-O2
PHER-O2, developed by Sanguine Corporation in Pasadena, CA, is a PFC with oxygen-carrying capabilities and reportedly few side effects. This drug is now under evaluation not only as a blood substitute for transfusion, but also as a therapy for heart attack and stroke.
HBOCs are manufactured from sterilized hemoglobin and look somewhat like real blood. These dark red or burgundy colored blood substitutes are often made from RBCs of expired human blood, cow blood, hemoglobin-producing genetically modified bacteria, or human placentas. The artificial hemoglobin molecules are modified to create a sturdy structure and to function without the protective cover of RBCS. Through a chemical process called polymerization, two or more three molecules bonded together to form a larger HBOC molecule. HBOCs are smaller than natural RBCs. While natural RBCs remain in the bloodstream for about 100 days, HBOCs circulate in human blood for only a day. Side effects of HBOCs may include elevated blood pressure, abdominal discomfort, and a temporary reddish coloration of the eyes or skin.
Hemopure
Hemopure, sponsored first by Biopure Corporation and later by OPK Biotech, is currently used in hospitals in South Africa. This oxygen therapeutic drug was approved by the Government of South Africa because of the country’s widespread HIV contamination of the blood supply. However, it recently has been targeted for removal from the market in South Africa. Hemopure is made from chemically stabilized, cross-linked cow hemoglobin using a fairly simple and less expensive biotechnology than required for other HBOC blood substitutes. Its minute size – not more than 1/1000 the size of RBCs – is advantageous for transporting oxygen into small spaces between cells. Compared to human donor blood, Hemopure delivers oxygen more quickly to target areas of the patient’s body.
PolyHeme
PolyHeme, sponsored by Northfield Laboratories in Chicago, is a first-generation polymerized hemoglobin-based oxygen-carrying hemoglobin solution. It was developed after the Vietnam War for emergency treatment in trauma situations of blood major loss. In the mid-2000s Polyheme was compared with donor blood in a clinical trial of more than 700 people in a US Phase III Trial. Patients receiving Polyheme had a slightly higher rate of negative side effects such as high blood pressure, inflammation, and multiple organ failure compared with the control group. (The small size of the PolyHeme molecule causes it to bind with nitric oxide, leading to constricted blood vessels.) However, here was no difference between the drug and control groups in the survival rate at 30 days. Although Northfield Laboratories has stopped manufacturing Polyheme, scientists and doctors working with this artificial oxygen carrier claim that more research is needed before its benefits versus risks can be conclusively determined.
MP4OX (Hemospan)
MP4OX (formerly known as Hemospan), sponsored by Sangart of San Diego, is a promising powdered form of artificial blood that can be mixed with liquid for transfusion. It is made from expired human blood combined with an added compound, polyethylene glycol, to minimize toxicity. With a capacity to enhance oxygen transfer
from RBCs to tissues, MP4OX is designed to supplement the body’s own ability to transport oxygen. Currently in Phase II trials in the United States, MP4OX effectively raised oxygen levels in patients without serious side effects.
Hemotech
Hemotech, produced by HemoBiotech in Dallas, TX, is a proprietary, chemically modified hemoglobin manufactured from cow blood. It was originally developed in 1985. With a shelf life of more than six months, if has shown no signs of toxicity in clinical studies. Hemotech is currently approved by the FDA for Phase I trials in the United States.
Engineered Hemoglobin
Scientists at the University of Essex in the United Kingdom are evaluating a new patent-pending engineered hemoglobin to serve as a blood substitute. The novel molecule is designed for optimal oxygen delivery. If successful, this innovative blood substitute could deliver a rich supply of oxygen to the tissues with almost no toxicity to the body.
The red blood cells coursing through your veins transport the oxygen necessary for your survival, and if you lose blood during surgery or in an accident, for instance, you must seek donations. But instead of relying on the blood bank, researchers are now working to make their own supplies. Some start with biological materials, modifying cow's blood or coaxing stem cells to make the much-needed oxygen carriers. Others hope to craft synthetic materials into blood cell substitutes that may deliver not only vital oxygen, but also medicine. Here, we look at five blood technologies in development.
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Artificial Blood Is Patient-Ready
In the midst of news that
engineered organs are being implanted into animals and people,
researchers announce the creation of artificial blood for transplant.
A new source of blood could be just around the corner: red blood
cells grown from fibroblasts that have been reprogrammed into mature red
blood cells in the lab. The blood, developed by researchers at the
University of Edinburgh and the Scottish National Blood Transfusion
Service (SNBTS), would be Type O negative, also known as universal donor
blood, which currently comprises just 7 percent of the blood donor
pool.
“We have made red blood cells that are fit to go in a person’s body,”
“Although similar research has been conducted elsewhere, this is the first time anybody has manufactured blood to the appropriate quality and safety standards for transfusion into a human being,” Turner told The Telegraph.
The artificial blood could be transfused into patients in a clinical trial setting as early as 2016, likely for three patients suffering from a genetic disorder called thalassaemia, in which the body makes unusually low levels of hemoglobin—a problem that is treated frequent transfusions.
Correction (April 17): This story has been updated from its original version to correctly reflect that the researchers are deriving blood cells, not serum, from iPSCs, and that the cells themselves are not artificial. The Scientist regrets the errors.
Artificial Blood Substitutes
– Update on the Promise of a Medical Breakthrough –Blood substitutes — also called oxygen therapeutics or hemoglobin-based oxygen carriers (HBOCs) — offer the promise of new and important life-saving medical treatments.
Blood is a vital, life-sustaining fluid that picks up oxygen in the lungs and then carries it to the heart and the rest of the body. Blood performs many functions such as transporting nutrients from the digestive system, removing toxins and waste, and fighting germs.
Blood is composed of a watery substance called plasma as well as three different types of cells or parts of cells that float in the plasma. The formed elements are red blood cells (RBCs), white blood cells (WBCs), and platelets.
White blood cells are part of the body’s immune system that destroys viruses and bacteria, the pathogens that cause infections. Platelets form clots to prevent bleeding from cuts and small wounds. RBCs account for more than 90% of the formed elements in the blood.
These abundant cells transport oxygen and carbon dioxide via blood vessels called arteries and veins. RBCs are disc-shaped with a large surface area for absorbing and releasing oxygen.
These cells do not have a nucleus in the center, but instead contain a complex molecule — hemoglobin (Hb) — that collects and releases oxygen.
Blood Transfusion
If a patient looses too much blood during a traumatic injury or a surgical operation, he may need a blood transfusion. Despite the nation’s numerous blood banks, there is a critical shortage of human blood available today for medical purposes. Nearly 33% of Americans will need a lifesaving blood transfusion at some point in their lifetime.With 4.5 million Americans receiving blood transfusions each year, the number of patients requiring blood is now outpacing the number of blood donors. Although the American blood supply is generally safe, small amounts of the blood stored in blood banks may be contaminated with HIV and hepatitis virus.
Limitations
Human blood has other limitations as well. It must be stored at a cool temperature and it has a shelf life of only 42 days. For these reasons, blood may not be readily available when needed in an emergency situation — on the battlefield or in an ambulance transporting an injured, bleeding patient to the hospital.The need for safe artificial blood is even greater for many people outside the United States. In sub-Saharan Africa, for example, blood loss accounts for an estimated 44% of women who die in childbirth. In many countries in the Developing World, blood is not screened for infectious pathogens that cause HIV, hepatitis, and syphilis.
Artificial Blood Advantages
Artificial blood has several advantages over human blood. Because blood substitutes belong to the universal blood group O negative, they can be given to patients regardless of their blood type. Patients administered artificial blood will not experience immunologic reactions, but they would face serious health problems if they received incompatible donated blood.When blood substitutes are manufactured they can be sterilized to destroy bacteria and viruses. This eliminates the risk for infectious diseases in a blood transfusion – a major issue in many parts of sub-Saharan Africa. With a longer shelf life than human blood, some blood substitutes can be stored for one to three years without refrigeration.
Artificial blood can be safely shelved outside hospitals and then rapidly administered to patients in emergency situations. Also, patients whose religious beliefs prevent them from accepting blood from donors would benefit from blood substitutes such as PFCs that are not derived from blood products.
Oxyglobin
Oxyglobin is the only blood substitute approved for use in veterinary medicine in the United States and Europe. A safe and effective blood substitute is urgently needed for human blood transfusions in hospitals, at accident sites, and on battlefield filled with injured military workers. An efficient oxygen-transporting blood substitute for humans would also be an important therapy for aplastic anemia and swollen tissues in sickle-cell anemia.Over the last three decades medical scientists have made some progress in the discovery of human blood substitutes. Currently, two main types of artificial blood products — hemoglobin-based oxygen carriers (HBOCs) and perflourocarbons (PFCs) — are either being tested or are already on the market for human use.
To be effective, a blood substitute has to function like hemoglobin in carrying oxygen to organs and cells inside the patient’s body. The problem, however, is that hemoglobin outside of RBCs is toxic. Pure hemoglobin injected into the body causes blood vessels to tighten, leading to high blood pressure, capillary collapse, and sometimes heart attacks, strokes, and death.
Without its RBC wrapping, hemoglobin can produce swelling and fevers. These unwanted side effects are one of the main reasons why blood substitutes made from hemoglobin are so difficult to make.
HBOCs and PFCs
Pharmaceutical companies attempted to develop HBOCs (also called oxygen therapeutics) and PFCs starting in the 1980s and at first seemed to have some success. However, the results of most human clinical trials have been disappointing. A study published in 2008 the Journal of the American Medical Association summarized the results of 16 clinical trials on five different blood substitutes administered to 3,500 patients.Those receiving blood substitutes had a threefold increase in the risk of heart attacks compared with the control group given human donor blood. However, a closer analysis of the results showed that some of the negative statistics were misleading.
The artificial blood products reviewed in this study varied in their benefits and risks, and some blood substitutes had very few serious side effects. The findings suggest that some blood substitutes may be safer and more beneficial than scientists originally thought.
Summary of Key Blood Substitutes Approved, In Clinical Trials, or Withdrawn
Blood Substitute
|
Blood Substitute Class
|
Clinical Trials
|
Approval
|
Fluosol-DA-20 | PFC | Clinical Trials completed in 1980s: Discontinued due to side effects | Approved in 1989;Withdrawn in 1994 |
Oxygent | PFC | Phase Clinical III trials: Increased risk of stroke | No Approval; Phase III trials stopped |
Perftoran | PFC | Completed (Russia) | Approved in Russia, Mexico |
Oxycyte | PFC | Phase II Clinical Trials (traumatic brain injury) umderway in Switzerland and Israel | No Approval; Further research needed |
PHER-O2 | PFC | Pre-clinical Trials umderway | No Approval’ Further research needed |
Oxyglobin | HBOC | Trials completed by late 1990s: Canine anemia | Approved: Veterinary Medicine |
Hemopure | HBOC | Completed (South Africa) | Approved (South Africa); May be withdrawn |
PolyHeme | HBOC | Phase III Trial (U.S.): Increased side effects in treatment group; no difference in 30=-day survival rate | No Approval; Further research needed |
MP4OX (Hemospan) | HBOC | Phase II Trials (U.S.): Raised oxygen levels without serious side effects | No Approval; Further research needed |
Hemotech | HBOC | Phase I Trials: No toxicity | No Approval; Further research needed |
Engineered Hemoglobin | HBOC | Preliminary studies: Minimal side-effects; good oxygen delivery | No Approval; Further research needed |
Perfluorocarbon (PFC) Blood Substitutes
Perfluorocarbons (PFCs) are totally synthetic artificial blood products derived from fluorine- and carbon-containing chemicals. They are chemically inert, but more effective than water or blood plasma in dissolving and absorbing oxygen in the lungs and then transporting oxygen throughout the body. PFCs remain in the bloodstream for about 48 hours. Because of their oxygen-dissolving ability, PFCs were the first group of artificial blood products studied by scientists. They are the first generation blood substitutes. Unlike the red colored HBOCs, PFCs are usually white. However, since they do not mix with blood they must be emulsified before they can be given to patients. PFCs are such good oxygen carriers that researchers are now trying to find out it they can reduce swollen brain tissue in traumatic brain injury. PFC particles may cause flu-like symptoms in some patients when they exhale these compounds.
Examples of PFC Blood Substitutes
Fluosol-DA-20
Fluosol-DA-20, manufactured by Green Cross of Japan, was the first and only oxygen-carrying blood substitute ever to receive approval from the FDA. Although approved in 1989, it was withdrawn in 1994 because it was cumbersome to administer to patients and it had side effects.
Oxygent
Oxygent, developed by Alliance Pharmaceutical Corporation in San Diego, is a PFC-based oxygen carrier currently approved for Phase II trials in both Europe and the United States. Oxygent initially showed promise for decreasing the need for donated blood during surgery. However, phase III trials were stopped recently because patients receiving Oxygent showed a higher risk of stroke compared to controls receiving donor blood.
Perftoran
Perftoran, sponsored by Moscow, Russia, is a PFC emulsion approved for human use in Russia in 1996. In 2005, the same drug was registered and approved as an authorized blood substitute for use in Mexico under the trade name Perftec, distributed by KEM Laboratory in Mexico.
Oxycyte
Oxycyte — a third-generation perfluorocarbon (PFC) therapeutic oxygen carrier sponsored by Synthetic Blood International in Costa Mesa, California — is designed to transport oxygen to damaged tissues and carry carbon dioxide to the lungs for removal. With an oxygen-carrying capacity up to five times that of hemoglobin, Oxycyte may be beneficial for traumatic brain injury, sickle cell crisis, heart attack, and wound care as well as for blood transfusion. It has been approved for Phase II clinical trials on traumatic brain injury in Switzerland and Israel, but more research is needed before it can be deemed safe and effective as a blood substitute.
PHER-O2
PHER-O2, developed by Sanguine Corporation in Pasadena, CA, is a PFC with oxygen-carrying capabilities and reportedly few side effects. This drug is now under evaluation not only as a blood substitute for transfusion, but also as a therapy for heart attack and stroke.
Hemoglobin-based Oxygen Carrier (HBOC) Blood Substitutes
HBOCs are manufactured from sterilized hemoglobin and look somewhat like real blood. These dark red or burgundy colored blood substitutes are often made from RBCs of expired human blood, cow blood, hemoglobin-producing genetically modified bacteria, or human placentas. The artificial hemoglobin molecules are modified to create a sturdy structure and to function without the protective cover of RBCS. Through a chemical process called polymerization, two or more three molecules bonded together to form a larger HBOC molecule. HBOCs are smaller than natural RBCs. While natural RBCs remain in the bloodstream for about 100 days, HBOCs circulate in human blood for only a day. Side effects of HBOCs may include elevated blood pressure, abdominal discomfort, and a temporary reddish coloration of the eyes or skin.
Examples of HBOC Blood Substitutes
Hemopure
Hemopure, sponsored first by Biopure Corporation and later by OPK Biotech, is currently used in hospitals in South Africa. This oxygen therapeutic drug was approved by the Government of South Africa because of the country’s widespread HIV contamination of the blood supply. However, it recently has been targeted for removal from the market in South Africa. Hemopure is made from chemically stabilized, cross-linked cow hemoglobin using a fairly simple and less expensive biotechnology than required for other HBOC blood substitutes. Its minute size – not more than 1/1000 the size of RBCs – is advantageous for transporting oxygen into small spaces between cells. Compared to human donor blood, Hemopure delivers oxygen more quickly to target areas of the patient’s body.
PolyHeme
PolyHeme, sponsored by Northfield Laboratories in Chicago, is a first-generation polymerized hemoglobin-based oxygen-carrying hemoglobin solution. It was developed after the Vietnam War for emergency treatment in trauma situations of blood major loss. In the mid-2000s Polyheme was compared with donor blood in a clinical trial of more than 700 people in a US Phase III Trial. Patients receiving Polyheme had a slightly higher rate of negative side effects such as high blood pressure, inflammation, and multiple organ failure compared with the control group. (The small size of the PolyHeme molecule causes it to bind with nitric oxide, leading to constricted blood vessels.) However, here was no difference between the drug and control groups in the survival rate at 30 days. Although Northfield Laboratories has stopped manufacturing Polyheme, scientists and doctors working with this artificial oxygen carrier claim that more research is needed before its benefits versus risks can be conclusively determined.
MP4OX (Hemospan)
MP4OX (formerly known as Hemospan), sponsored by Sangart of San Diego, is a promising powdered form of artificial blood that can be mixed with liquid for transfusion. It is made from expired human blood combined with an added compound, polyethylene glycol, to minimize toxicity. With a capacity to enhance oxygen transfer
from RBCs to tissues, MP4OX is designed to supplement the body’s own ability to transport oxygen. Currently in Phase II trials in the United States, MP4OX effectively raised oxygen levels in patients without serious side effects.
Hemotech
Hemotech, produced by HemoBiotech in Dallas, TX, is a proprietary, chemically modified hemoglobin manufactured from cow blood. It was originally developed in 1985. With a shelf life of more than six months, if has shown no signs of toxicity in clinical studies. Hemotech is currently approved by the FDA for Phase I trials in the United States.
Engineered Hemoglobin
Scientists at the University of Essex in the United Kingdom are evaluating a new patent-pending engineered hemoglobin to serve as a blood substitute. The novel molecule is designed for optimal oxygen delivery. If successful, this innovative blood substitute could deliver a rich supply of oxygen to the tissues with almost no toxicity to the body.