Abstract
Blood transfusion administration is mandatory for clinical surgeries as well as emergency rescues. Blood is often reserved in blood banks awaiting use. However, blood storage lesion results in changes that affect the red blood cells hence changing the quality of blood as it ages. This paper articulates the negative properties of old blood which include; low ATP, reduced coagulation abilities, and increased risk of infection from pathogens. This factors increase the risk of a person developing complications from receiving old blood. The paper also highlights the need for old blood since fresh blood may be unable to satisfy the demand. It is noted that current research focuses on advancing storage media technology to decrease blood degradation. The paper concludes by reasserting that while old blood puts most patients at a risk due to changes in its metabolic, molecular and biochemical changes during the storage lesion, it will still be used in transfusions due to shortage in availability of fresh blood.
Introduction
Blood is the liquid that gives life and the unique function of blood was acknowledged by man many civilizations before the scientific era. The invention of blood transfusion methods proved to be a monumental advancement in medicine since it increased the chances of survival for people who would otherwise have died from blood loss. Blood transfusion administration is mandatory for clinical surgeries as well as emergency rescues1. For this reason, there exist blood banks which store donated blood to be used when it is needed. The rationale behind having blood in banks is that fresh blood may not always be readily available and in case of emergencies, having blood available in the freezers may save lives. There have been concerns about the effects of storage on blood with arguments being raised that storage period affects the quality of blood. According to Price2, old blood causes numerous health problems to patients transfused with it. This assertion is corroborated by other researcher1, 3 who declares that blood develops some damages while under storage. This affects the health of the patient receiving the old blood. Despite these revelations, old blood continues to be used since blood donation at times can be below a nation’s blood demand and availability of fresh blood might be hard. This paper will set out to argue that old blood is bad blood. To reinforce this claim, the paper will make use of current research on the topic from various authorities on the subject. To provide a balanced view on the topic, the paper will also review research in support of old blood. The paper will then analyze the implications of this information to human health.
Research on Blood Storage
Blood banking has undergone major developments over the past century. In the past, blood was preserved by use of soluble salts such as oxalic acid and sodium citrate3. While the salts ensured that the blood didn’t coagulate, it was impossible to preserve it for even a few days. Robertson used Rous-Turner medium which is a combination of a nutritive substance and an anticoagulant which lengthened the storage period to twenty one days3. The anticoagulant used in the preservation of blood brought about citrate toxicity and thus with advancement its levels in the preservation media has been reduced. There has also been an introduction of Purine nucleosides in the storage media which assist in the maintenance of ATP and 2, 3 – diphosphoglycerate. This has improved the quality of the red blood cells that have been transfused. As a result of advances in storage technology, blood can now be stored for up to 42 days. This ability has resulted in the availability of old blood which is defined as blood which is over 18days old 4. A lot of research has been dedicated to identifying the effects of long storage on blood. Findings indicate that some complications such as: respiratory, cardiovascular, organ failure and infections may arise from using damaged blood1, 2, 4.
Storage lesion is the factor responsible for the deterioration of blood with age. Storage lesion is defined as the assemblage of the changes that affect the red blood cells thus causing irreversible damage reducing the post-transfusion period4. The red blood cell membrane physically becomes altered leading to abnormalities of the cells metabolism5. To sustain functional hemoglobin there is need for maintenance of the red blood cell membrane and its ability to negotiate capillary beds. This is dependent on the energy metabolism of the Red blood cells which it derives from glycolysis that help to boost the energy level of phosphate bonds of ATP. The preservative media used thus need to consider having an ingredient that maintains the appropriate red blood cell energy metabolism or the ATP level. Focus was therefore turned to this major component known as the ATP.
Negative Attributes of Old Blood
The storage period of blood in a blood bank is known as shelf storage life. This has a direct relationship to the levels of ATP. For blood to be effective in the body it’s ATP (Adenosine 5 -triphosphate) needs to be at work and in the right amount6. ATP is found in almost every cell in our body. Extracellular ATP which is involved in sustaining the circulatory system: the heart, blood vessels and muscles. How much of it is in any cell then determines the survival and function of the cell in question. In older blood though the ability of the red blood cells to release this major molecule is limited and thus causes blood to get stuck to the walls of the blood vessels thus causing the previously mentioned complications.
One of the processes of blood is coagulation where blood forms clots to prevent loss through damaged vessels. This process is critical since without it, a person could easily bleed out from a minor wound. Studies indicate that storage of RBCs has an effect on the coagulation process7, 8. The Activated Clotting Time was prolonged as the age of PRBCs increased. It can therefore be stated that the universal coagulation standing is adversely affected by the storage of the PRBCs that are transfusable. A study by Aucar et al reveals that storage lesion can impair the role of RBCs in promoting coagulation7. The authors therefore suggest that old blood should not be used for acute trauma since prolonged storage adversely affects the coagulation system.
RBCs undergo numerous morphological and biochemical changes during storage. Ran et al1 (p 1) state that morphological changes occur to blood during storage and the normal structure of red blood cells disappears. This negative effect is further increased by irradiation and filtration. However, filtration and irradiation are necessary since they reduce the risk of viral transmission in the blood. The red Blood cell is biconcave disc shape in nature. During the storage period it changes into a crenated sphere with long spicules known as spheroechinocyte4. This change in shape affects surface area to volume ratio reducing it. According to Nakao et al5 (p 945) other changes that go along way with these physical changes are increase in: mean cell hemoglobin concentration (MCHC), osmotic fragility, depletion in ATP and deformability. Old red blood cells have a reduced GPA, CD44 and CD147 as from the twenty eighth day of storage. The CD44, CD147 and CD58 are known as cell adhesion molecules (CAMs).The drop in expression of the CD47 on the red blood cells increases the authorization in the circulation of red blood cells9. Other membrane molecules like glycophorin a (GPA; DC235a) and the translocation of aminophospholipid, phosphatidylserine (PS) to the external membrane contribute to RBCs storage lesion. These cellular constituent which also include annexin V also pave way for cell disintegration and damage7.
A major issue that affects the quality of blood available in blood banks is the infections from pathogens and leukocytes contamination. To diminish infection in the primary stage of blood collection aseptic techniques are used to reduce bacterial infection4. Deterioration of blood in the blood bank might begin in the initial stages due to various factors which include; the speed of blood collection and mixing, how the blood was transported and how well the 24 hour pre-processing storage time was used8. Blood that has had a longer storage has proved to cause numerous post-operation complications and mortality after undergoing a cardiovascular operation. According to a study that was carried out in Cleveland Clinic foundation a conclusion was drawn that patients who were transfused with blood more than 2 weeks old developed complications after the surgery and their survivor period was reduced8.
Other viral infections have been greatly reduced by use of enhanced donor screening and testing. Methods that have been used to curb viral infections are Nucleic acid testing (NAT) and use of enzyme assays for surrogate markers3. With these developments viral threat has not been totally eliminated instead new challenges come up when we have new viruses coming up. The greatest risk in blood transfusion is that of malaria and HIV especially in Africa. This is also contributed to the weak medical economy that cannot sustain the expertise to test and produce blood which is free from infections especially in the developing countries.
A Case for Old Blood
For all the arguments presented against old blood, it is still useful for medical purposes. Hess reveals that some of the negative impacts of old blood are as a result of the material used to store blood, DEHP10. This statement is corroborated by the US National Toxicology program which has expressed concern over the ‘possible effects of high exposures to DEHP on the development of the genital tract of male neonates’10 (p 56. Current red cell storage systems are less than optimal since they render RBC unrecoverable sooner than they might. While shortening the duration of storage of RBC will solve the problem of accumulated DEHP, alternative plasticizers would completely eliminate DEH hence making old blood non-toxic.
Contamination of blood mostly occurs during the first 24hrs of processing. Research indicates that 0.05% of blood is contaminated with bacteria at the time of collection10. This contamination is either from the skin of the donor or from blood-borne bacteria. Interestingly, most bacteria do not survive the cold temperatures that the blood is stored in. Even so, some bacteria are cold-tolerant and continue to multiply even under storage and are transmitted to the new host on transfusion. As such, old blood is not inherently bad rather is made bad due to poor handling. In addition to this, the quality of blood received and stored is greatly dependent on the health of the donor. This assertion is true since blood that contains infections such as bacteria and viruses will be hazardous for use regardless of whether it is used fresh or old. The quality of blood in the blood banks is dependent on the technology used in screening, collection and storage of it. Since a lot of care and research has been put forward to ensure that the blood in the blood banks globally has the same standards, this problem can be projected to end in the near future.
One of the damages attributed to stored blood is oxidative damage. This is the damage to lipids and proteins which results in the injury of RBC. Hess notes that oxidative damage occurs in the human body as well10. In fact, the damage in stored RBC is lower as a result of the lower temperature at which the blood is stored. Since the standard storage of RBC is 6weeks, it is significantly shorter than the 120 day life of RBC in the human body. As such, the cumulative oxidative damage in old blood is significantly less than what would be expected in a human body.
Blood is typically stored at the low temperatures of 4⁰C and since the red cells are stored cold, many units are administered cold9, 10. This has the effect of reducing the temperature of the person who is receiving the blood transfusion. Research indicates that if 10 units or more are administered to a person rapidly, the blood may have an adverse effect on the person9. This fatality will occur regardless of whether the blood used is young or old.
Current and Ongoing Research
While old blood does pose some challenges, the reality is that blood levels may fall lower than the needed levels in a country so reliance on fresh blood may not be the solution toward sustaining patients need. It’s therefore necessary to be able to know how to make old blood useful without causing harm to our health11. Research on blood especially the old one in the blood banks has not yet been exhausted there are various areas that are still being researched. One of these is these is more outcomes after blood transfusion and the alternative for the same. It is not clear the best transfusion trigger or hermatocrit that can be used with cardiovascular surgery. There is need for research to establish a globally accepted transfusion rates for heart surgery patients instead of individual institutions administering their own triggers. Another area that is undergoing research is the effects related to corpuscular injury instead of focusing on byproducts in the storage medium2, 10. This assists in the improvement of blood to be transfused. Clarification of storage lesion on oxygen is also underway to examine its consequences over transfusion of red blood cells.
What Is Still Unknown or Under Investigation
A primary function of RBC is to transmit oxygen to cells throughout the body. If the oxygen delivery capability of blood was compromised, the usefulness of the blood would be greatly diminished. Research is yet to convincingly determine whether storage time affects the ability of RBCs to load and unload oxygen. Despite several attempts by scientists to demonstrate the effects of storage on oxygen delivery to tissue, conclusive results have yet to be given10.
The storage time of Red blood cells and leucocytes burden of the concentrate influence the nature of storage lesion but what needs to be established for it’s not known is whether reduction of GPA and CAM on the RBCs external membrane can have a negative effect on its function and survival in post transfusion4. Investigating the blood banking practices that will enhance use of the blood that is in close proximity to the finish of its storage life in relation to coagulation and ACT of the PRBCs. This would help in the improvement of providing quality and risk free blood.Hereby then transfusion and blood banking would be as intended to improve the health of the patients and not compromising it.
Information that we have
Researchers have focused their attention to how old blood can be preserved and made safe for use by patients. This is on the premise that patients need to be protected from having their health compromised after a transfusion. Several researches have been conducted with the aim of understanding what happens to blood before transfusion, how well to improve the quality of stored blood and how to lengthen the life of this blood7, 9, 11. From this research works, a number of discoveries have been made. Hess declares that the discovery that the supermatants of stored red blood cells, but not those of fresh red cells contain lysophospholipids that cause transfusion related lung injuries is a clear example of the dangers that stored blood posses11.
Research has enabled us to know that old blood puts most patients at a risk due to changes in its metabolic, molecular and biochemical changes during the storage lesion. The red blood cells are damaged by many factors like Leucocytes related factors like cytokines and enzymes3. Other factors are protein and lipid peroxidation and metabolite depletion. These factors do affect the RBCs storage lesion and possibility of post transfusion. How the blood is handled even at the initial stages from extraction, containers used and even the extractions made on the blood interfere with the usefulness of that blood10. Any mishandling of it can be fatal to the user. CPD is used as the anticoagulation media used in blood storage for it contains phosphates7. Additives need to be added nutrients like glucose for use by ATP molecules which are used to boost the cells metabolic functions thus it improves the survival of the RBCs at least to half life. Mannitol has been used to increase the post transfusion life of blood by 6 weeks in the blood bank. Residual plasma is used to store blood about 10% of it. Leukocytes have been greatly reduced in stored blood decreasing the risk of transmitting diseases for anti immunal depressants is kept at a minimal level12.
Impact of this information
As a result of the negative attributes associated with old blood, many medics have their preference on fresh or young blood in relationship to the old blood. A study by Vamvakas and Carven explicitly linked length of storage of transfused blood to frequency of postoperative pneumonia11. This demonstrates that old blood may indeed be bad for the patient. Hess10 reveals that a few deaths have been reported as a result of the high potassium and lysophospholipids additive solutions used to store RBC in liquid suspension. While these deaths are markedly rare, they still pose a problem since in an ideal situation; blood transfusions should be 100% safe. Despite these, Almac and Ince4 state that there is inadequate evidence against old red blood cells and as such, it is unrealistic and unnecessary to advice patients to use fresh RBCs. Even so, many authors12 suggest that for critically ill patients, fresh RBCs which are devoid of the damage associated with old RBCs should be used.
Infection too as noted earlier can be from the containers that are used to store the blood. For example containers made of DEHP-PVC have a DEHP plasticizer which causes decline in hemolysis in the packs10. It has an antioxidant and membrane stabilization effect making it to have a reduction in cellular injury in storage but this advantage is reduced by the fact that they are known to introduce carcinogen in humans. Containers made of CLX, which are non-leachable, are used instead. There is a universal implementation of pre-storage leukocyte reduction which is beneficial for decreasing immunosuppressant and alloimmunisation10.
Conclusion
This paper set out to argue that old blood is bad blood. To reinforce this claim, the paper has discussed the various effects that long storage has on the quality of blood. It was stated that advancements in storage techniques have improved storage times and at the present time, blood can survive for up to 42days. This has led to the availability of old blood which is blood which is older than 18days. This paper has acknowledged that RBCs undergo significant biochemical and morphological changes during storage, and this affects the quality of RBCs. The quality of blood is therefore degraded with prolonged storage. As a result of this, there are some dangers associated with using old blood. The effect of this dangers are however only adverse if blood is transfused in large quantities or if the recipient is critically ill. All in all, this paper has shown that there is a negative relationship between the storage time and red blood viability. It can therefore be authoritatively stated that old blood indeed is bad blood.
References
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