The Newly Examined Additive Solution(S) In Comparison SAG-M Medium
Posted: Jan 09, 2019
Describe The Main Factors Contributing To Storage Lesion And Discuss The Efficacy Of The Newly Examined Additive Solution(S) In Comparison SAG-M Medium
Red Blood Cells (RBC) transfusion is a clinical procedure which is considered vital for saving a life. Severe injuries, as well as medically associated disorders that contribute to reduced oxygen carrying capacity, need RBC transfusion. However, RBC gets damaged soon after leaving the body. Therefore an effective and efficient preservative system for maintaining the integrity of RBC is significant. Initially, the transfusion of blood was easy since blood was easily available. Traditionally donor and recipient were connected vein to vein. Currently, demand for blood transfusion has gone high. Increased demand of RBC has triggered many researchers to develop methods and techniques for preserving RBC . Various biopreservation approaches have been introduced to facilitate long term and short term RBC preservation techniques. The main goal of various preservative techniques is to maintain safe and readily available RBC products. The goal of developing preservatives is to maintain viability, functionality, and integrity of RBC within ex vivo environment. The main purpose is to increases chances of safety and efficiency in blood transfusion process.
RBC storage lesion contributes the various effects on the storage of RBC and the impact encountered after transfusion. The paper provides factors contributing to storage lesion as well as brief overview of various factors. It also provides a discussion about the available additive solutions towards RBC storage systems.
Hypothermic Storage of RBC
Hypothermic temperatures are freezing points of storage solution below normal physiological temperature. The hypothermic condition is based on principals that cell metabolism slows down with reduction of temperature. The decrease in metabolic processes results to depletion in the rate of biochemical activities . Reduced chemical reactions slow down cellular metabolism and diminish the accumulation of waste products. The reduction in temperatures guarantees longer RBC preservation in the presence of hypothermia preservative solution. Preservative solutions provide RBC contents with proper nutrition, proper PH levels, as well as adequate sources of metabolic energy. The environment provided by hypothermic solution guarantee RBC viability, functionality, and high quality .
Shortcoming of RBC Hypothermic Storage
Hypothermic stored RBC undergo a series of changes during the storage process. The changes that occur during RBC banking are referred to as hypothermic storage lesion. During the storage, there are factors that contribute to storage lesion . They can be classified into two types of changes namely biomechanical and biochemical changes.
Biomechanical Factors Leading to Storage lesion
The most identifiable biomechanical changes that occur during hypothermic storage include changes due to injuries on erythrocyte membrane and cytoskeleton . The following factors contribute the biochemical changes or biochemical storage lesson
- Protein oxidation
- Lipid peroxidation
- Membrane phospholipids redistribution
- Membrane phospholipids loss through microsimulation
- Reduction in surface area to volume ratio
- Increase in intracellular viscosity
The above factors lead to changes in RBC morphology and deformation. Oxidation of cytoskeleton causes protein oxidation and lipid peroxidation. Oxygen and iron ions that are highly concentrated in ligand state RBC called Hemoglobin. However, an oxygen and iron content gets lost during RBC storage resulting in Hemoglobin oxidation. Protein oxidation leads to the phospholipids loss as a result of RBC microcirculation . Membrane lipid peroxidation contributes to damaging of the cell. RBC plasma membrane is a factor that contributes to the distribution of phospholipids between the inner and outer layer of an RBC cell. Phospholipids found on RBC membrane are maintained by the energy as well as ATP-dependent amino-phospholipids enzymes. Loss of membrane asymmetry results to the appearance of phospholipids in the outer membrane. RBC cells lose phospholipids symmetry during Hypothermic storage process making RBC cells affected to be removed from circulation . Such occasion reduces the number of RBC viable for transmission.
Another factor contributing to biochemical storage lesion is phospholipids loss through microvesicular. RBC microvesicles or microparticles contain hemoglobin, phospholipids, proteins as well as protein antigen. They coordinate communication between different cells. RBC microcirculation is a mechanism of a cell to clear itself from phospholipids concentration on the outer surface . RBC microsimulation increases during hypothermic storage. This increases the number of RBC which are eliminated from circulation. There are other biomechanical factors contributing to storage lesion during hypothermic. Others include progressive morphological and structural change of RBC from biconcave shape to echinocyte . It may also reveal some characteristics such as spicule formation, or spherical shapes. Such factors lead to deformation of RBC, increased RBC aggregation, and high adhesion to endothelial cells.
Biochemical Factors Leading to Storage Lesion
Metabolic reactions cause biochemical factors leading to storage lesion. The major chemical associated with changes include depletion of adenosine triphosphate (ATP) and disappearance of 2, three diphosphoglycerate (2, 3 DPG) . Cell viability is determined by the concentration of ATP . During RBC storage ATP levels declines resulting in declining in viability. RBC glycolytic metabolism contributes to consumption of ATP energy and at the same time reduces production of ATP. as a result concentration of acid PH becomes high in the cell. Due to lack of normal ATP concentration many cellular processes are affected such as lack of enough sodium and potassium responsible for normal cell osmotic balance. It also affects membrane structure as well as the stability of the cell.
Intracellular RBC ATP depletion during hypothermic storage leads to storage lesion through causing sodium ions and potassium ions to become inactive. Loss of potassium ions and sodium ions contributes to erythrocyte deformation, a decrease of hemolytic volume, as well as membrane changes that contribute to lipid loss via microsimulation leading to reduced surface area to volume ration. ATP reduction affects the production of Nitric Oxide which is enhanced vasodilatation during a blood transfusion. Similarly, depletion of 2,3 DPG affects RBC functionality thus causing high influences on the storage lesion . 2,3 DPG helps in binding and enhancing hemoglobin to adapt to the amount of oxygen available. Decreased concentration of 2,3 DPG during RBC storage increases hemoglobin affinity for oxygen. This results in a situation whereby RBC are not capable of delivering sufficient oxygen to the tissues. Therefore during transfusion process before the restoration 2, 3 DPG to normal maintains efficient concentration and supply of oxygen in the tissues may be difficult. Other factors associated with the biochemical factors that lead to the storage lesion include S-nitrosothiol (SNO). SNO bioactivities decline during hypothermic storage. Loss of SNO in hemoglobin affects the release of NO compound from SNO hemoglobin . The effect may alter the ability of RBC for delivering oxygen to various cells. Other factors that lead to storage lesion include biochemical injuries such as
- The decrease in the pH
- The increase in intracellular calcium
- Oxidative damage which affects the RBC functionality as well as viability
The above factors contribute to occurrence of other factors such as
- Morphological changes
- Membrane loss
- RBC membrane injuries
- Lifestyle Factors
Lifestyle factors are likely to contribute to storage lesion. Donor’s health status, as well as hematological conditions during blood donation, can lead to storage lesion. RBC from some donors may have the more likely hood of getting easily oxidized. RBC may m also been influenced by mechanical stress that can affect reactions during storage and transfusion process. Blood donations vary based on a particular age group and sex . For example, most of the blood donated from young female donors may be characterized by the presence of mechanical stress. Similarly, post-menopause women may also contribute to storage lesion. Problems with menstrual cycle complications may also experience difficulties with blood transfusion. Some aspects of life such as feeding habits, performing body exercises, consumption of alcohol as well as smoking are also loop holes for making it easy for one to experience oxidation and mechanical stress during blood storage .
The solution to the discussed factors that contribute to storage lesion is improving the quality of hypothermic storing of RBC. The research should focus on developing methods for examining and modifying RBC chemical and physical characteristics during hypothermic storage.
RBC Additive Solutions
The first additive solution was discovered in 1970’s called Saline Adenine Glucose (SAG). The solution solved the issues of RBC membrane depletion and destruction through the use of mannitol. The solution reduced the hemolysis process . The solution facilitated storage of RBC in about six weeks refrigeration which could maintain up to 55 or 60% cells. Later SAG was modified, and its efficiency improved. It was later named SAGM which is one of the widely used additive solutions . SAGM is recommended for storing RBC for six weeks, but many countries usually use it for five weeks. However, SAGM has not been approved by Food and Drug Administration (FDA). Some alternative additive solutions for SAGM include:
The above solutions provide a high improved environment for preserving of RBC compared to storage environment provided by SAGM . Some of the benefits and advantages applied in using the above alternative addition solution is due to decreased hemolysis, as well as reduced shedding of microparticles. The above named additive solutions are licensed as RBC additive solutions . They are characterized by having a normal physiological pH of about 7.3. However, some modifications such as acid additive solutions that facilitate anticoagulation effects can be applied. Acidic solutions facilitate sterilization of heat energy.
The new RBC additive solutions have highly improved intracellular environments that alter activities of enzymes. They have promoted the ability of RBC to generate more Adenosine 5 tri-phosphate (ATP) and 2,3 Diphosphoglycerate (2-3 DPG) . The improvements have led to the high survival of RBC cells by facilitating the rate of delivering oxygen during storage. The current additive solutions have improved blood inventory management supply through the provision of techniques that can be applied for shipping blood supplies from one area to another. Remote areas have greatly gained benefits of accessibility and supply of sufficient blood without contaminations . RBC additive solutions have offered further improvements on blood transfusion through improved quality and efficiency of RBC blood components.
Most of the factors leading to storage lesion have been solved. The new RBC additive solutions have included an important component called alkaline solution that facilitates chloride shifting during RBC storage. The chloride ions facilitate the provision of equilibriums between the charged ions as well, as intracellular and extracellular mediums . During deficiency or decline state of an RBC cell, the chloride ions can leave the cell without carrying any other diffusible anions. In response, the hydroxide ions are capable of entering them cell and raise the intracellular pH. The new solutions have alkaline storage buffers for storing adequate glucose. It is capable of enhancing processes such as sterilization using a two pack system that prevents glucose caramelisation . The systems are designed such that each solution has one pack containing alkaline solutions while the other pack contains glucose solution. The existence of the new solutions in such manner has facilitated the provision of safe longer life by extending life of RBC by two weeks.
The various benefits gained with the current RBC is a justification of a successful transfusion of blood. Maintenance and quality of RBC components transferred to patients have greatly improved. The processing procedures associated with acquiring compatible, blood group has been made easy. Patients can get already collected and stored blood. Different samples of blood can be collected randomly thus increasing chances of obtaining compatible blood groups which are rare and difficult to find.
RBC Additive Solutions
RBC additive solution
AS-1 Adsol Baxter
AS-3 Nutricel Pall medical
AS-5 Optisol terumo
PAGGSM Maco pharma
Europe, UK, Australia,
Canada, New Zealand
Table1: RBC Additive Solutions
Retrieved from: https://www.researchgate.net/publication/230749659_Time_to_revisit_red_blood_cell_additive_solutions_and_storage_conditions_A_role_for_omics_analyses
Challenges for Introducing RBC
The major challenge facing development and implementation of new RBC additive solutions is the cost. The financial burdens, as well as risks involved in development and implementation of solutions, have led researchers to avoid investing in generating new RBC additive solutions . Manufacturers of blood collecting and storing systems take a long period to obtain license. The Very low market also characterizes RBC storage systems returns thus discouraging manufacturers due to low-profit margins. The FDA policies have become more strict by increasing more advanced assessment criteria for approving RBC additive solution. The policies have highly discouraged manufacturers from bringing their blood storage systems in the market . Similarly, the technology required for developing the new storage systems is highly expensive to purchase and maintain.
The study research has analyzed various factors that contribute to RBC storage lesion. The session has concentrated on the importance of developing an effective and efficient system for ensuring quality and intensity of RBC components are maintained and retained during storage and transfusion. The session has covered biochemical and biomechanical factors that contributes to the RBC storage lesion. The metabolic pathways and the structural appearance of the RBC cells has been identified as major affecting quality and survival of stored RBC. The study has facilitated significance of developing improved RBC storage components. The session has enhanced better understanding of various RBC additive solutions and their contributions in the current blood transfusion process.
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