Red Blood Cell Lesion for Cardiac Surgery Patients

Introduction

Storage lesions are changes in the red blood cells that occur in the course of storage before the blood is redistributed to a recipient. Innate functioning of the red blood cell is affected by the storage conditions, resulting in the deterioration of the cell membrane with increased storage time, thereby reducing the viability and usability of the cells with the passage of time. In this review, the paper delves into explaining the phenomenon of cell storage lesions and evaluating the effects of lesion on cardiac surgery patients, both adult and pediatric.

Describing Cell Lesion

Storage lesions refer to the various changes in red blood cells during storage processes. Over time as blood glucose is consumed, potassium levels become higher as ATP and 2, 3-diphosphoglycerate lower. The result is that there is a significant loss in cell membrane resulting in rheological changes to the cell. The loss of cell integrity occurring at this stage could result in micro-particle formation and hemolysis, thereby contributing to challenges associated with blood transfusion (Dern, Brewer, & Wiorkowski, 1967). In fact, multiple studies have found that using older blood for transfusion has led to adverse clinical outcomes. Nevertheless, some studies are yet to establish that these associations exist (Walsh, et al., 2004). Using old blood for transfusion still remains an issue of debate among clinicians. Nevertheless, the use of blood transfusion as a large-scale therapeutic approach needs to be subjected to further study on its impacts and possible mechanisms for the reduction of risks. In the first part of this review, an explanation of storage lesion and different mechanisms suggested to disturb homeostasis could affect storage lesion. 

The Role of Nitric Oxide

Nitric oxide is a radical molecule, neutral in nature, which plays several critical roles in physiological signaling processes. It is derived from the endothelial as a relaxing factor (EDRF). Manufactured in the endothelial cells, the nitric oxide plays an important role to control blood flow by enabling the relaxation of muscles which are next to the blood vessels (Furchgott & Zawadzki, 1980). The NO synthase in the endothelial cells makes the gas from arginine and is diffused to smooth muscles. Here, guanylyl cyclase is activated to produce cGMP, which essentially leads to the signaling processes which culminate in vasodilation. An additional two isoforms (both inducible and neuronal NOS) ensure the inhibiting of platelet aggregation, thereby contributing to homeostasis. Moreover, they act as toxic agents to the host defenses, provide anti-oxidant advantages and reduces adhesion molecule expression. Furthermore, red blood NOS has recently been discovered. Consequently, nitric oxide (NO) contributes to multiple functions involved in storage lesion, including thrombosis, blood flow and inflammation. 

Nitric Oxide Interaction with Hemoglobin

Nitric oxide naturally reacts with hemoglobin, where nitric oxide specifically reacts to the heme group in hemoglobin in a reaction captured below. The reaction is rate limited by diffusion.

Oxygenated hemoglobin reacts with nitric oxide to find methemoglobin and a nitrate compound, thereby destroying the activity of nitric oxide in the blood. Moreover, it is possible that the nitric oxide could bind with a vacant ferrous heme, thereby becoming less susceptible to deoxygenation. The result is that this reaction provides a poor mechanism through which NO bioactivity occurs. Lancaster (1994) established that the large amounts of hemoglobin within the blood alongside prevailing deoxygenation reactions would effectively prevent NO from acting as the required EDRF within these environments (Lancaster, 1994). The NO would undergo too much deoxygenation to effectively function. Nevertheless, it was discovered afterwards that NO is required is smaller amounts for hemoglobin encapsulated in red blood cells compared to that in free solution or plasma, as it is more difficult to react with RBC-encapsulated NO. in fact, where NO was reacted with hemoglobin present in red blood cells, the reaction was found to be almost one thousand times slower than where the reaction occurred with free hemoglobin. Specifically, this reaction rate was significantly reduced because of diffusion time required for NO to move into the red blood cells to obtain the hemoglobin. It is also possible that the limited permeability of the red blood cells towards NO plays a role in reducing this. On the other hand, reduced Nitric Oxide scavenging done by red blood cells is primarily suspected to be occurring in the cell-free zone. Blood flow results in a pressure gradient, which pushes the red blood cells to vessel center regions, away from the endothelial cells where NO is present. Nevertheless, it is important to understand that hemolysis results in the breakdown of all these mechanisms. 

Red Blood Cells Breakdown Pathology

Given the multiple roles played by nitric oxide, diminished nitric oxide availability will most certainly contribute to the pathology of multiple diseases. Most of these diseases occur as a result of endothelial dysfunction occurring once there is reduced NO synthesis in the NOS. some of these diseases include obesity, coronary artery disease and atherosclerosis among others. Aside from reduced NO production, bioavailability challenges could also result from increased consumption. In this manner, reduction occurs as a result of increased scavenging of NO by cell-free hemoglobin once hemolysis occurs. It has been indicated in the previous section that nitric oxide in the blood reacts up to 1000 times faster than NO encapsulated within the red blood cells. Consequently, NO scavenging is a major contributor to the pathological features associated with prescribed blood substitutes aiming to increase hemoglobin-based oxygen carriers. In such cases, only milli-molar hemoglobin amounts are infused. 

Contrary to popular thinking that conditions like sickle cell disease that cell-free hemoglobin is too low to affect nitric oxide availability in comparison to RBC-encapsulated hemoglobin, studies have found the opposite to be true. These studies evaluated sickle cell disease patients and found that micro-molar amounts of cell-free hemoglobin resulted in reduced responsiveness of blood flow following NO activity. Moreover, cell-free hemoglobin in the smallest concentrations could have widespread effects on blood flow, a fact that was substantiated in the canine hemolysis model. Computational analyses indicate that one micro-molar of cell-free hemoglobin could result in substantial nitric oxide availability. Consequently, studies have indicated that transgenic and large animals as well as humans accrue negative impacts from hemolysis with regards to their development of sickle cell disease. By extension, other sickle cell activity could be explained by the hemolysis phenomenon. Be it as it may, this assertion still remains to be universally acceptable. Despite different contributions negating the impact of hemolysis on NO bioavailability, the evidence of the impact is substantial with continuing evidence necessary to establish this body of knowledge. This assertion is considered largely by research as true since large hemolysis amounts and the pathological consequences it accrues remain uncontested. 

Breakdown of Red Blood Cells and Storage Lesions

Hemolysis occurs once red blood cells lose integrity during storage and instead form micro-particles. Studies have indicated that hemolysis is a natural occurrence after some time of storage. Different extracellular hemoglobin levels have been reported, where in heme values range around 28 μM to 80 μM following fifty storage days. For transfusion of a single unit of blood with similar hemolysis levels results in a plasma level that go over that present in sickle cell disease in a steady state. Moreover, studies have also indicated that nitric oxide consumption in the non-erythrocytic fraction is no greater for older blood compared to that stored for a week, and NO consumption remains proportional to its own extent for any given blood sample. 

The breakdown of red blood cells results in the formation of micro-particles containing hemoglobin apart from the release of cell-free hemoglobin. This situation is so much so that measuring cell-free hemoglobin does not prioritize efforts to consider micro-particles separately from cell-free hemoglobin. Further, some cases found that hemoglobin found in the blood in form of micro-particles was more than that existing in cell-free state. Their small size could indicate that micro-particle hemoglobin scavenges in a manner similar to cell-free hemoglobin. As such, the diffusion rate of NO to hemoglobin is the only factor that slows down the NO scavenging rate because the reaction is dependent on the distance between micro-particles. For instance, for a red cell with a radius of 3 μm and a micro-particle with 0.075 μm as its radius, NO diffusion is expected to be up to 2000 times longer compared to that of the normal micro-particle. Also, their small size means that shear stress is not sufficient to remove micro-particles from the cell-free region. Permeability reductions that are present in red blood cells are not present for micro-particles since the underlying spectrin and other proteins are not present. Consequently, all three methods through which NO scavenging is reduced in RBC scenarios are absent or reduced in micro-particles. In essence, micro-particles affect NO bioavailability in more extreme manners than cell-free hemoglobin, since micro-particles cannot be cleaned out by haptoglobin. 

Reduced NO bioavailability that further lead to increased scavenging of NO could be further accentuated by a lower count of red blood cells or even reductions in NOS. such reductions could occur in response to oxidative stress with red cell storage – a phenomenon associated with NOS protein uncoupling due to tetrahydrobiopterin oxidation and the deficiency of arginine. When NO synthase uncoupling occurs, the superoxide from NOS is formed, instead of the regular nitric oxide. In another scenario, NO bioavailability could be reduced once stored red cells are infused after diminished NOS activity, which remains active in other blood cells. 

Evaluating the Effects of Inflammation

Various studies have indicated that transfused red blood cells could augment inflammation using a number of mechanisms. Previously, it has been displayed that transfusing red blood cells increases both lung and systemic inflammation in mice, thereby resulting in chemokine-mediated accumulation of neutrophil as well as lung injury – phenomena that were RBC- and storage-dependent. Red blood cells that are transfused have also been found to result in the production of inflammatory cytokine responses which normally occur as a result of the mononuclear phagocyte system ingesting membrane-encapsulated hemoglobin. There is increased hemolysis and formation of micro-particles in the case of human red blood cell units. However, there is only little known about the effect of free hemoglobin and its membrane-encapsulated counterpart, especially with regards to the formation of micro-particles and the subsequent effect on inflammation for humans. Recent findings in the area indicate that the red blood cell micro-particles in banked blood have inflammatory chemokine binding properties and could release ligand when interacting with platelets. It is currently unknown whether red blood cell micro-particles play a part to increase inflammation, although sickle cell disease characteristics could indicate that this relationship exists. 

Associating Storage Lesion with Cardiac Surgery Outcomes

In this section of the paper, outcomes for different forms of cardiac surgery are evaluated based on available literature on the subject. 

Patients Undergoing Coronary Artery-Bypass Surgery

Prolonged red blood cell storage alters the cells and their storage media, resulting in a phenomenon known as storage lesions. In the course of time, the level of adenosine triphosphate within the cell decreases, thereby resulting in a cell membrane which is quite fragile and less deformable (Kim‐Shapiro, Lee, & Gladwin, 2011). This breakdown results in the release of hemoglobin within the blood, as well as micro-particles – a phenomenon whose population could result in reduced NO bioavailability. This leads to inflammation, vasoconstriction and thrombosis. In the case where there is increased depletion of 2, 3 DPG, there is even less oxygen delivery to critical organs. Various studies have provided the clinical impacts of cell lesions of the red blood cells. 

For instance, there are several studies which have evaluated the storage time of red blood cells and clinical outcomes for cardiac surgery patients. Previously, such studies have used a variety of patients, including those who underwent open heart surgery or on-pump coronary bypasses. Notably, cardiac diseases involving valves have different pathophysiology depending on their types and severity. For example, cardiopulmonary bypass involving hypothermia normally consists metabolic, inflammatory and hematological responses in addition to organ injury, so that transfusing stored blood to the patient becomes a more complication process. In this case, the off-pump coronary artery bypass was selected, as it was a rather rare investigative area for the effect of storage lesions, as Min et al (2014) contemplated. 

According to Min et al (2014), the transfusion rate for red blood cells for off-pump surgery was lower than that of on-pump surgery although more than half of these patients required this transfusion. Adequate oxygen delivery necessitated that patients receive transfusion. As a result, old blood could increase concern for the vascular effects that follow. In their study, the authors hypothesized that prolonged blood (and red blood cells) storage was associated with adverse hospital effects for their patients. The result is that the study resulted in investigation in-hospital outcomes in comparison with the RBC storage time for the off-pump patients. Both adverse cardiovascular and cerebral events were recorded for the patients. 

The study reported that the oldest transfused red blood cells were associated with all in-hospital reports of adverse outcomes for the patients. This results remained relevant even after factoring in confounding factors in the case of post-operative wound complications. Furthermore, the number of transfused red blood cells significantly correlated with outcomes on all patients after factoring in confounding factors. The mean age for transfused red blood cells did not affect the clinical outcomes, as there was no significant relationship. However, where red blood cell units were no older than 14 days had significant impact on some post-operative outcomes such as wound complications and bleeding reoperation. An excerpt of this table is presented below: 

Table 1 : Results for Off-Pump Coronary Artery Bypass Clinical Outcomes on RBC Age (Min, et al., 2014).

Table 3
The age or the number of transfused RBCs and the postoperative clinical outcomes
		Univariate analysis			Multivariable analysis
	N (%)	OR	95% CI	P value	OR	95% CI	P value
Number of transfused RBCs
In-hospital all-cause mortality	17 (1.6)	1.1	1.07-1.14	<0.001	1.1	1.06-1.14	<0.001
In-hospital MACCEs	74 (6.9)	1.06	1.04-1.09	<0.001	1.05	1.03-1.08	<0.001
New renal failure	54 (5.0)	1.05	1.03-1.07	<0.001	1.03	1.00-1.05	0.04
Respiratory complication	33 (3.1)	1.05	1.03-1.07	<0.001	1.04	1.01-1.06	0.005
Postoperative wound complication	49 (4.6)	1.04	1.02-1.06	<0.001	1.03	1.01-1.06	0.001
Atrial fibrillation	290 (29.1)	1.04	1.02-1.06	<0.001	1.02	1.00-1.04	0.038
Arrhythmia other than atrial fibrillation	112 (10.4)	1.05	1.03-1.07	<0.001	1.03	1.02-1.05	<0.001
Bleeding-related reoperation	29 (2.7)	1.09	1.06-1.12	<0.001	1.08	1.05-1.12	<0.001
Oldest age of transfused RBCs
In-hospital all-cause mortality		1.1	1.02-1.19	0.015	1.01	0.91-1.12	0.896
In-hospital MACCEs		1.01	0.97-1.05	0.63	0.97	0.93-1.02	0.198
New renal failure		1.08	1.03-1.13	0.001	1.03	0.98-1.09	0.251
Respiratory complication		1.07	1.01-1.13	0.02	1.01	0.95-1.08	0.726
Postoperative wound complication		1.1	1.05-1.15	<0.001	1.09	1.04-1.14	0.001
Atrial fibrillation		1.03	1.00-1.05	0.022	1.01	0.99-1.04	0.339
Arrhythmia other than atrial fibrillation		1.04	1.00-1.07	0.037	1.02	0.98-1.05	0.348
Bleeding-related reoperation		1.08	1.02-1.15	0.007	1.02	0.95-1.10	0.531
Mean age of transfused RBCs
In-hospital all-cause mortality		0.93	0.84-1.04	0.23	0.95	0.82-1.09	0.446
In-hospital MACCEs		0.95	0.90-1.00	0.053	0.95	0.90-1.01	0.1
New renal failure		0.99	0.93-1.05	0.684	1.01	0.94-1.08	0.857
Respiratory complication		0.99	0.92-1.06	0.731	0.98	0.90-1.06	0.629
Postoperative wound complication		1.04	0.98-1.10	0.201	1.05	0.99-1.12	0.106
Atrial fibrillation		1	0.97-1.03	0.969	1	0.97-1.04	0.783
Arrhythmia other than atrial fibrillation		0.99	0.95-1.03	0.614	1	0.96-1.05	0.869
Bleeding-related reoperation		1.04	0.96-1.12	0.332	1.08	0.99-1.18	0.094
Any RBCs unit >14 days
In-hospital all-cause mortality		1.83	0.64-4.84	0.225	0.7	0.20-2.45	0.278
In-hospital MACCEs		1.02	0.64-1.64	0.933	0.74	0.44-1.24	0.256
New renal failure		1.5	0.87-2.60	0.148	1.05	0.57-1.97	0.869
Respiratory complication		1.54	0.77-3.09	0.224	1.06	0.50-2.27	0.878
Postoperative wound complication		1.96	1.10-3.50	0.023	1.71	0.93-3.12	0.083
Atrial fibrillation		1.2	0.92-1.58	0.18	1.06	0.80-1.41	0.675
Arrhythmia other than atrial fibrillation		1.41	0.95-2.09	0.085	1.19	0.79-1.80	0.407
Bleeding-related reoperation		2.24	1.05-4.75	0.036	1.21	0.50-2.93	0.669

The study found that the total number of transfused red blood cells was significantly related to the duration of stay at ICU for the patient as well as their hospital stay in totality. When the effects of transfused RBCs were controlled, older red blood cells were associated with longer hospital stays, but no relationship was found for the length of ICU stay for the patient. Moreover, the relationship between the age of the red blood cell and base excess on the first morning following the operation. For older red blood cells, there was a significant negative correlation that was present for post-operative base excess, but other age groups for red blood cells could not establish any relationships (Min, et al., 2014). 

Total bilirubin levels were obtained post-operation to determine the levels of hemolysis in patients. Bilirubin was present for patients who had more amounts of red blood cells transfused into them and where these cells were much older. However, when the transfusion amount was adjusted, older age red blood cells were not found to affect the amount of bilirubin within the patient’s body. Wound complications were also observed for patients. The study noted that there was a significant relationship occurring between the age of transfused red blood cells and wounds occurring post-operation. Using a quartile presentation of red blood cell wounds, the study was able to determine that older red blood cells resulted in higher instances of wound complications for patients compared to newer blood samples (Min, et al., 2014).

Retrospective Analysis

Post-operative outcomes were associated with transfused red blood cell amounts for patients who had undergone off-pump coronary artery bypass surgery. When adjusted for confounding factors, the age of the transfused blood was associated with wound complications, post-operative base excess and the length of the patient’s hospital stay. Moreover, a linear relationship was displayed for transfused blood age and wound complications after the operation. To this end, there are multiple studies that have contemplated the impacts of the storage time of red blood cells for patients with cardiac surgery requirements. A previous study did not give the storage time of red blood cells as a significant predictor of the mortality of the patient (Van Straten, et al., 2011). Moreover, where early postoperative morbidity was present, alongside other adverse cardiovascular events, blood age was not associated with such clinical outcomes. As a result, Min et al (2014) provided findings that were consistent with those of other studies, but realized a finding that was not evaluated for other studies – the effect of older blood on wound complications. 

Studies evaluating this outcome found that transfusion for blood older than 14 days resulted in increased mortality, reduced long-term survival rate, mechanical ventilation time increase and a number of other complications (Koch, et al., 2008). Nevertheless, these results did not consider differences between newer and older blood grounds and how these factors could have affected outcomes (Van De Watering, Lorinser, Versteegh, Westendord, & Brand, 2006). More so, there was no difference in the number of wound complications associated with different age blood transfusions and the number of on- and off-pump surgeries for this instance remained unknown. These differences were clarified by the results in the study conducted by Min et al. (2014). 

Flowing from these results and those posted by others on the subject, it was found that storing red blood cells for more than 14 days was considered hazardous, as this is often the point where patient grouping is cut off. Intracellular decline of 2, 3 DPG is undetectable after 14 days, although this level is revitalized completely after 72 hours of transfusion. Adverse effects of the red blood cell transfusion on morbidity and mortality after the operation has also been provided in multiple studies (Vamvakas & Carven, 2000). Similar to those studies, Min et al (2014) displayed that RBC transfusion resulted in longer hospital stays and long-term outcomes on the patient in a manner that was consistent with similar studies in the area. 

For some wound complications, there have been reported increases in body mass index and diabetes outcomes for patients, thus becoming additional risk factors (Vymazal, Horácek, Durpekt, Hladíková, & Cvachovec, 2009). Min et al (2014) found results similar to these. Older age RBCs often resulted in increased incidence of postoperative wound complications although a causal relationship could not be established. Acid-base status was also marked in the postoperative session to determine the effectiveness of oxygen delivery to tissues and amount of cell perfusion. Negative base excess was found to be correlated with the older aged red blood cell transfusion, which could result in insufficient supply of oxygen to tissues. It is possible that older blood transfusions could result in tissue hypo-perfusion – a factor which increases the incidence of wound complications thereby lengthening one’s hospital stay. 

The fact that NO bioavailability is limited at this stage could also delay one’s wound healing, as nitric oxide has been found as a necessary component for wound healing. Nitric oxide is synthesized specifically in the initial stages when the wound is healing. It improves the processes by giving angiogenesis processes, forming collagen, fibroblast migration from damaged tissues as well as cell proliferation. In conclusion, the study observed that in-hospital outcomes were associated with red blood cells transfused to the patient. Where older units were transfused, such patients experienced higher incidences of wound complications, negative base excess and longer stays at the hospitals, but other hospital outcomes were limited.

The Case of Pediatric Cardiac Patients

Redlin et al (2014) contemplated the case of pediatric cardiac patients and the impact of red blood cell lesions on clinical outcomes. Notably, stored red blood cells are often transfused after five days. In the course of this storage time, red blood cells are altered for that their function, quality and viability are affected – these changes are what this paper refers to as lesions. With limited consensus among scholars regarding the impact of these lesions in older and fresh-cut cells, this study evaluated the impact that such RBCs would have in the wake of increased infections and morbidities following the transfusion of older blood. Of course, the study noticed the numerous studies that have not found correlations between patient outcomes and storage time for the transfused blood. Perhaps, these disparities could be explained by the differences in study designs and groups of patients and the different measures used to obtain outcomes. Furthermore, different studies used up to 27 days as the cutoff point for viable red blood cells. Again, some of these studies did not control groups to determine those who had received old blood compared to those who had received new. The result is that few studies have exclusively considered patients for old or new blood. 

Redlin and cohorts contemplated transfusion in the case of pediatric open heart surgery using cardiopulmonary bypass. This particular method was used due to imbalances for pediatric patient blood volumes and their priming volumes at the CPB circuits. Two other studies have reported that blood storage for such patients required a cutoff point of less than five days to avoid postoperative morbidity. These studies indicated that using the freshest blood available for such patients is best, limiting choices to 14 days blood. The study therefore considered patients who received RBCs that were between 0 and 14 days in storage lengths for the purpose of the study. Different clinical outcomes were measured, including morbidity and CRP concentration as a measure of inflammation in the patient. 

139 pediatric patients were considered for the study, with their mean age being 14 days. Most of the patients had combined defects and a section had undergone previous sternotomies. 26 patients received blood that was stored for up to 3 days whereas 113 patients received blood stored for more than 3 days. Older pediatric patients were transfused using older blood. Patients who received fresher RBCs often required lower volumes than those receiving older blood.

Retrospective Analysis

Essentially, this study supported the prioritization of using fresh blood for pediatric cardiac patients. To demonstrate this, it was noted that the requirement for transfusion volume increased with the increase in storage duration of the blood. Optimal cut-off times for transfusion for greater volumes of blood was at 2 days. Moreover, the ventilation duration post-operation and the CRP concentration was affected for blood which had been stored more than 6 days. 

It was found that older blood was required to be transfused in larger amounts, similar to previous studies that indicated that older blood increased the transfusion requirement. The study conducted by Redlin (2014) specifically avoided mixing blood so that patients would specifically display the benefits accrued from singular unit receptions. Patients who used single units of fresher blood required less amounts. Such views are supported by multiple scholars who noted that mixing blood affected the design of observational studies intended to determine the impact of storage time on outcomes. The heterogeneous amount of differently-grouped RBCs in such a scenario affect proper observation. Such problems could not be accounted for, even where transfused RBC units were adjusted. This study, therefore, eliminated this problem by providing marking mechanisms for the age of red blood cells. 

In contrast with other studies, the age of red blood cells for this study was maintained below 14 days. Individual RBC storage time was determined by availability of units. The cut-offs thereby provided the study with adequate understanding to perform analysis. The only challenge with such a system would be the inapplicability of cohorts that utilized longer storage timelines. In any case, the patients displayed profound effect of the transfusion requirements and morbidity following RBC storage time, even though all samples were considered fresh. Effects of storage time in adults following cardiac surgery is widely described, although storage time had no effect on mortality or ICU length of stay, especially after contemplating the number of transfusions. The study involving pediatric patients considered a single unit of red blood cells. The storage time for the RBCs was found to influence ventilation length, peak CRP concentration and the total volume of RBC transfusion requirements for the patient. The study conclusively found that shorter storage times could have significant effects on both the pediatric patient’s morbidity and transfusion requirements. 

Concluding Thoughts

Storage lesions are an effect accruing to red blood cells as a result of the length of their storage before being engaged in blood transfusions. Due to the length of stay outside the body, red blood cells undergo changes that result in the change of their physical and mechanical function. The result is that the cell becomes more fragile as it spends more time in storage. From the review of literature above, storage conditions that exceed fourteen days could have hazardous effects on the blood, rendering it no longer useful for transfusion, especially for patients who have undergone cardiac surgery.

The first part of this paper sought to describe the phenomenon of storage lesions and how they occur in the body. The role of nitric oxide in the body was described, as well as its unique role in the proper functioning of the red blood cell. Nitric oxide as a controller of vasoconstriction was contemplated. Moreover, instances where nitric oxide availability is lacking was equally considered as a gateway to increased cardiac stress post-operation and a factor that contributes to increase hemolysis, micro-particles formation and poor health outcomes. Pathophysiology associated with hemolysis was also contemplated where the role of cell-free hemoglobin and RBC-encapsulated hemoglobin was contemplated in light of changing cell structures. Thereafter, inflammation was considered as an after-effect of excessive hemolysis occurring subsequent to storage lesion. 

In the first review of literature, storage lesions were considered in the case of patients who had undergone off-pump coronary artery bypass surgery. Different clinical outcomes were evaluated, including patient’s morbidity, wound complications and base excesses. This study found that longer storage of red blood cells was associated with longer hospital stays, increased incidence of postoperative wound complications and a negative base excess within patients. Nevertheless, mortalities were limited in their occurrence post-operation, although there was a reduced post-operative lifespan for patients receiving older blood. A second review of literature was conducted to consider the outcomes of pediatric cardiac patients undergoing open heart surgery. Different clinical outcomes were observed, including patient’s RBC requirement, CRP (inflammation) measure and use of ventilation machine length. The study resolved that patients transfused with fresher red blood cells required a lower amount of transfused units compared to patients using older blood. More so, there was lower CRP readings for patients receiving fresher units and such patients were associated with shorter ventilation machine usage time. 

From the two studies evaluated above, there is tangible evidence indicating the effect of storage lesions on clinical outcomes for cardiac surgery patients. Specifically, patients who have received fresher units of red blood cells often have better clinical outcomes in terms of their hospital stay durations, the durations of using ventilation machines, their transfusion unit requirement as well as negative base levels and inflammation levels. Using fresher units of red blood results in lower incidences of postoperative wound complications. 

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