HAEMATOLOGICAL CHANGES IN STORED BLOOD AND ITS IMPLICATIONS

SEMINAR PRESENTATION

BY

ABDULLAHI ALIYU YAKUB

18/MHS06/001

PRESENTED TO THE DEPARTMENT OF MEDICAL LABORATORY SCIENCE, COLLEGE

OF MEDICINE AND HEALTH SCIENCES, AFE BABALOLA UNIVERSITY ADO-EKITI,

EKITI STATE IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD

OF BACHELOR OF MEDICAL LABORATORY SCIENCE (B.MLS) DEGREE

(HAEMATOLOGY AND BLOOD TRANSFUSION SCIENCE)

SUPERVISOR: MRS OYEGUE ESTHER

NOVEMBER, 2022
OUTLINE

 INTRODUCTION

 BLOOD STORAGE

 HAEMATOLOGICAL CHANGES IN STORED BLOOD

 IMPLICATIONS OF HAEMATOLOGICAL CHANGES IN STORED BLOOD ON

HEALTH

 MANAGEMENT AND PREVENTION OF HAEMATOLOGICAL CHANGES IN

STORED BLOOD

 CONCLUSION

 REFERENCES
INTRODUCTION

Blood storage (blood banking) is a process in which blood gotten from the

body that are not ready for use are stored. The blood bank serve as the

storage medium for the blood that is collected from donors separated into

different types and prepared for transfusion to the recipient; a blood bank

may be a separate free – standing facility or part of a larger laboratory in a

hospital (Patrick, 2021). About 36,000 units of blood are needed every day;

each unit of blood is broken down into components such as red blood cells,

plasma and platelets and transferred to several patients, each with

different needs, Blood that is not ready for use and is stored outside the

body may undergo changes due to storage, these alterations has

implications and repercussions for the blood and the stored bloods (Anon,

2013).
BLOOD STORAGE

Blood is first collected from donors and processed into different components,

after which they are stored until needed. Different storage processes of

different blood components are discussed below:

-RED BLOOD CELLS (RBCs) CONCENTRATE

It is obtained from the removal of supernatant of centrifuged whole blood

within 8hours of collection; the centrifugation is done at 3800-4000rpm for 5-7

minutes, Red cell concentrates (packed red cells) are prepared from a single

donor and consist of 220 mL of packed cells and 80 mL of plasma(Mark and

Dafydd, 2006).

STORAGE AND SHELF LIFE

RBC concentrates must be stored at 4 ± 2 °C in a suitable refrigerator or in a

cold room with continuous temperature control. RBC concentrates should also

be transported at temperatures between 1 and 10 °C (cold chain!). Concerning

their shelf life, the user is referred to the manufacturer’s specifications on the

product label of the preparations in question (Schlenke, 2009).

-PLATELET CONCENTRATE

This blood component is now in routine production and issued on demand. It

is gotten by centrifugation of platelet rich plasma (Anon, 2009).

STORAGE AND SHELF LIFE

In a platelet agitator and incubator employing a horizontal agitation, the

platelet concentrate are stored at 20-24 degree Celsius, they are usually stored

for 72 hours or five days prior to transfusion (Aubron et al., 2018).

-FRESH FROZEN PLASMA (FFP)

Fresh frozen plasma is the fluid portion of a unit of whole blood frozen, FFP is

the plasma separated from whole blood within 6 hours of collection through

centrifugation and rapidly frozen at -20 degree Celsius, Fresh frozen plasma is

the fluid portion of a unit of whole blood frozen (Hina et al., 2019).

STORAGE AND SHELF LIFE

It is stored at -40 degree Celsius or colder, it has a shelf life of 1 year, but it can

be extended to 7 years if stored at − 65 °C in an ultra-low temperature. If not

stored at this temperature the labile coagulation factors will deteriorate and
the amount are greatly reduced thereby defeating the purpose of which FFP is

to be transfused (Noordin et al., 2017).

-CRYOPRECIPITATE

Cryoprecipitate(Cryo) is a plasma-derived blood product, enriched for

fibrinogen(Fb), factorVIII(FVIII), factorXIII(FXIII) and von Willebrand

factor(vWF).The discovery of Cryo in the 1960s and its first indication as a

replacement for FVIII has led to great support to hemophilia A patients

(Kasper, 2012).

STORAGE AND SHELF LIFE

It is stored at -18 degree Celsius or colder for 12 months, from the original

collection date, there is no significant loss of activity for six months after

production after thawing, and thawed single cryoprecipitate and pooled

cryoprecipitate which are sterilely manufactured can be stored at 20-24

degree Celsius for up to 6 hours (Stubbs et al., 2019)

HAEMATOLOGICAL CHANGES IN STORED BLOOD

Stored blood has a potential to alter due to storage, some of the changes are

examined under the following hematological component:

-RED BLOOD CELLS (RBCs)

The primary physiological role of red blood cells is the supply of oxygen to

tissues, to accomplish this task; RBCs have unique flow-affecting properties,

which play a crucial role in blood circulation in health and disease (Barshtein et

al., 2021). Erythrocytes are highly specialized cells without nucleus, with a

limited metabolism; various changes associated with RBC storage include a

depletion of ATP21-23 and 2, 3-DPG, 22-25 membrane phospholipids

vessiculation and loss, protein oxidation and lipid peroxidation of RBC

membrane, and, ultimately, loss of deformability (Ferguson et al., 2021).

One of the main characteristics that determine the behavior of cells in the

bloodstream is deformability, During blood banking RBCs morphology changes,

which have been suggested to be associated with decreased deformability,

RBCs deformability is the cells ability to adapt their shape to the dynamically

changing flow conditions to minimize their resistance flow (Cluitmans et al.,

2014), RBC deformability is also a significant determinant of their ability to

pass through the splenic vasculature; thus, reduced deformability, which is

always the case in stored RBCs, it hinders their transit and increases splenic

RBC sequestration and destruction (Safeukui et al., 2012).It was reportedly

demonstrated that damage to RBCs caused by storage becomes prominent at

the beginning of 2nd week of storage, furthermore, this damage was noted to

progress with increasing storage duration(Xu et al., 2016). The deformation of

an RBC contains three modes: area expansion, shear, and bending of the cell

(Zhensong et al., 2018).The slightest damage to the deformability of RBCs

during storage is caused when leukofiltration is implemented during the

preparation of the unit, and the storage is carried out in SAGM(saline-adenine-

glucose-mannitol)solution (Barshtein et al., 2021).

Red cells stored for a longer period of time are clearly associated with reduced

recovery and temporary alteration in capillary blood flow. Red cell storage is

also associated with secondary risks from accumulating concentrations of

extracellular potassium; shed active proteins, lipids and micro-vesicles, and

bacterial contaminants. The clinical consequences of the majority of these

changes are unknown, but hyperkalemia can lead to cardiac arrhythmias

(Hess, 2010).

Efforts to increase the length of time that red blood cells can be safely stored

have centered on optimizing their glucose metabolism. Glucose breakdown,

glycolysis, is the red cell’s only source of energy, and 94% of glucose
metabolism in warm red cells is via the main glycoltic pathway through glucose

phosphate, fructose diphosphate, glyceraldehyde phosphate, and pyruvate

(Lewis et al., 2009).

The shape changes seen during red cell storage are associated with rheological

changes, increased viscosity, and reduced flow in capillary systems

(Henkelman et al., 2010)

Adenine, a component of both ATP and NAD, is broken down in the course of

red cell storage. Most of this breakdown occurs through the action of

adenosine deaminase which converts adenosine to inosine, Inosine is further

broken down to uric acid. The total uric acid load is small, however, and uric

acid stones or gout have not been a complication of the transfusion of stored

blood (Tinmouth et al., 2006).

The relationship between the changes observed in stored red cells in the

laboratory and the negative clinical outcomes ascribed to them need to be

linked by both plausible physiology and solid epidemiologic evidence (Hess,

2010).
-PLATELETS

Storing platelets in the cold cause’s structural, molecular, and metabolic

changes, this is often referred to as the cold platelet storage lesion (Getz,

2019). It was early recognized that platelet survival and recovery was

decreased when stored cold (Kristoffersen and Apelseth, 2019).

During storage, changes occur in both platelets (PLT) and storage medium,

which may lead to PLT activation and dysfunction (Aubron et al., 2018).

A major problem with platelet containers has been that some platelet units

show a dramatic fall in pH associated with overloading of the platelet storage

container. The basic events are well known: increased platelet glycolysis, as

evidenced by increased glucose consumption, increased lactate production

and, as a consequence, a fall in pH, but also a fall in ATP levels suggesting

insufficient energy supply (Gulliksson et al., 2012).

Unlike red cell or whole blood components, which are stored at 1-6 degree

Celsius, platelets are stored at 20 to 24 degree Celsius to preserve function and

survival, such storage makes them an excellent growth medium for a broad

spectrum of bacteria, multiple aerobic-culture surveillance studies have

demonstrated that 1 in 1000 to 2000 platelets units are bacterially

contaminated (Brecher and Hay, 2005). Gram-positive skin commensals such

as Staphylococcus epidermidis and Bacillus cereus are

the organisms most frequently recovered from given blood (and involved in

bacterial contamination of platelets, such contamination is thought to happen

basically during phlebotomy, as a result of inadequate cleansing of the

skin(including skin appendages where the disinfectant may not penetrate),

These organisms ordinarily do not develop at 1-6 degree Celsius but survive

and increase promptly at the platelets storage temperature of 20 to 24 degree

Celsius. Contaminated aphaeresis-derived platelets and pooled platelets were

the products most often contaminated by bacteria during storage (Brecher and

Hay, 2005).

-FRESH FROZEN PLASMA (FFP)

FFP contains clotting factors, albumin and other serum proteins, and plasma

protease inhibitor, FFP contains all stable and labile coagulation factors, such

as factor (F) V and FVIII. Upon request for blood transfusion, FFP is thawed for

30 min at 37 °C(Yazer, 2012).Duration of storage and different storage

temperatures might affect the coagulation factor activity in thawed FFP

(Noordin et al., 2017). In FFP, levels of plasma clotting factors are reduced in
 storage; therapeutic levels of FV and FVIII are maintained in thawed plasma

stored for up to 10 days at 1 to 6°C.Thawing of FFP at 45°C decreases thawing

time but does not affect the activity of FV, FVII, and FVIII (Tholpady et al.,

2012).

-CRYOPRECIPITATE

Cryoprecipitate helps in replenishing important coagulation factors like

fibrinogen, Factor VIII and von Willebrand factor without running the risk of

volume overload (Philip et al., 2014). One of the main uses of cryoprecipitate

was for the treatment of hemophilia A. Replenishing the thermo labile Factor

VIII levels, therefore, it has a major beneficial effect of transfusing

cryoprecipitate units and hence, the decline in its activity is a limiting factor

caused by prolonged storage of cryoprecipitate beyond 6 hours (Philip et al.,

2014).

IMPLICATIONS OF HAEMATOLOGICAL CHANGES IN STORED BLOOD ON HEALTH

During storage, blood experiences a sequence of cellular and other changes

which minimize their lifespan and purpose, and these changes have

implications on health (O et al., 2014). These implications include:

-Red blood cell (RBC) transfusions can be lifesaving, they are not without risk.

In critically ill patients, RBC transfusions are associated with increased

morbidity and mortality, which may increase with prolonged RBC storage

before transfusion(Hod et al., 2010).Observational studies suggest that

prolonged RBC storage before transfusion increases mortality, serious

infections, and multi organ failure in some hospitalized patients (Rapido et al.,

2016). 

-Adverse effects of transfusion may be mediated by changes in the blood

product that accumulate with storage time, the mechanisms, however, are

largely unknown. Erythrocyte-derived micro particles (MPs) have been found

in transfusion bags and their concentration increases with storage duration

(Kriebardis et al., 2012). Erythrocyte-derived MPs from red blood cell storage

induce a strong inflammatory response (Straat et al., 2014).

- A higher number of red blood cell units transfused seem to increase the risk

of acute lung injury, and the age of red blood cells under storage is associated

with respiratory failure requiring prolonged ventilator support, The process is

complex and may involve multiple mechanisms, including lysis of red blood
cells (hemolysis), oxidative stress and blood clot formation driven by micro

particles that form over time in stored blood (Lee and Gladwin, 2010).

- Red blood cells promote platelet-leukocyte interactions is still unclear, but

one possibility is haemostatic activation of platelets after encounter with

micro particles derived from red blood cells. Micro particles, characterized by

exposure of phosphatidylserine on their surface, provide a procoagulant

surface leading to thrombin generation. Haemostatic activation of platelets

may spatially link thrombosis and inflammation to amplify micro vascular

damage (Lee and Gladwin, 2010).

- Extension of platelet (PLT) storage duration may expose patients to potential

decreases in PLT transfusion efficacy as well as possible increases in adverse

events in addition to transfusion-associated sepsis, such as inflammation

and/or immune-mediated events (Aubron et al., 2018)

- Platelets undergo time-dependent structural and functional changes such as

mitochondrial damage, increased phosphatidylserine, metabolic failure,

membrane lysis and release of lactate dehydrogenase (LDH); that are

indicative of apoptosis (Schleicher et al., 2015)

 -Platelet preparation methods and storage time have been demonstrated to

affect haemostatic, endothelial, and immune function of PC. For example,

platelet storage increases phosphatidylserine(PS) expression on platelets,

which has prothrombotic effects and increases micro particle and soluble

mediator release, which may affect the immune status of platelet concentrate

recipients (Shea et al., 2019).

- Extended storage of thawed cryoprecipitate at room temperature may

increase the risk of bacterial contamination. Contamination may also occur as

a consequence of the processes used to thaw and store cryoprecipitate. This

leads to reports of cases of Pseudomonas septicaemia after transfusion of

cryoprecipitate (Soundar et al., 2018).

MANAGEMENT AND PREVENTION OF HAEMATOLOGICAL CHANGES IN STORED

BLOOD

-APPROPRIATE STORAGE BAG; various storage bag and storage media changes

have been proposed to reduce glycolysis and platelet activation during room

temperature storage. Moreover, cryopreservation and cold storage have been

proposed as potential methods to prolong platelets concentrate shelf life by

reducing platelet metabolism and bacterial proliferation (Ng et al., 2018).

-STANDARD STORAGE TEMPERATURE; Blood cold chain is an organized process

for blood storage and carriage in a secured manner from the time blood is

received from the donor till the time it is transfused to the patient, Because of the

fact that blood is a biological material, it is vital to keep it in a cold environment to

preserve the viability feature and improve the hematologic condition of the

patient (Aalaei et al., 2019), the process of storage of blood out of the standard

temperature range lead to some biochemical reactions. Infusing inappropriately

stored blood may cause severe complications (Shokoufeh et al., 2018). The

process of storage and carriage of the red blood cells (RBCs) out of the standard

temperature range leads to some biochemical reactions, these reactions cause

the blood to lose the ability to carry oxygen and carbon dioxide to/from tissues

while transfusing the blood (Yoshida et al., 2019). One of the main reasons of

preserving blood in the standard temperature is to minimize the bacterial growth.

If blood is kept beyond the higher defined limit, even for a short period of time,

the bacteria that are infiltrated into blood from the donor will quickly grow and

propagate (Aalaei et al., 2019). On the other hand, keeping blood in a

temperature less than the defined lower limit might damage the membrane with

resultant hemolysis that will increase mortality and morbidity, thus, it is

absolutely necessary to monitor the temperature changes of blood products,

characterize the potent failure locations, investigate the influential reasons and

modify them. This can prevent adverse events including death, development of

organ failure, infection, and long hospitalization (WHO, 2005), A temperature

monitoring device can be employed to better monitor the blood banking

processes and compensate for the unnoticed temperature by blood bank

personnel (Alaei et al., 2019).

-ACCURATE STORAGE DURATION; Failure to follow correct storage time of blood

may result in decreased transfusion efficacy, potential harm to the patient or the

component being unsuitable for use and discarded. It was repeatedly

demonstrated that damage to RBCs caused by prolonged storage becomes

prominent at the beginning of the 2nd week of storage, Furthermore, this

damage was noted to progress with increasing storage duration as a part of the

storage lesion, donated RBCs lose their deformability due to the prolonged cold

storage (Barshtein et al., 2021), therefore, it is essential accurate storage duration

is to be followed in storing blood and blood products in the blood banks.

CONCLUSION

Blood storage (blood banking) has encountered challenges, including changes in

haematological components of the blood that may be structural, molecular, or

biochemical. These issues can be resolved by using appropriate storage bag,

maintaining the recommended storage temperature and accurately timing the

duration of storage to ensure quality of stored blood.

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