INTRODUCTION
Platelets (thrombocytes) are the smallest among other major blood cells (K. Ghoshal & M. Bhattacharyya, 2014; Mokhtar et al., 2016). Their main function, along with the coagulation factors, is to prevent bleeding (K. Ghoshal & M. Bhattacharyya, 2014). Fragments of cytoplasm originated from the megakaryocytes of the bone marrow (BM) define platelets structurally (Bhasin et al., 2013; Riedl et al., 2017). Platelets appear as dark purple spots on a stained blood smear (Fig. 1), and they are about 20% of the diameter of RBCs (Ford, 2013; Kakali Ghoshal & Maitree Bhattacharyya, 2014b; Laki, 1972). 150,000-350,000/^l is the normal platelet count, but because platelets are small, they just make up a small fraction of blood volume. In the healthy adults, the ratio of platelets to RBCs is 1:10-1:20 (George, 2015). The contribution to hemostasis is the main function of platelets, although they have many different functions in the circulation (Gupta et al., 2020; Periayah et al., 2017). The processes to halt bleeding at the injury’s site or interrupted endothelium are sequences as follows (Fig. 2) (Yip et al., 2005):
- Adhesion: thrombocytes attach to substances located outside the injured area.
- Activation: platelets force themselves to change their shape, turn on receptors, release chemical messengers.
- Aggregation: the connection of thrombocytes to each other throughout the receptor bridge takes place.
During these processes, a platelet plug (primary hemostasis) is formed, leading to a coagulation cascade activation and in turns depositing of fibrin at the site of injury (secondary hemostasis). Thus, the clot is formed, and the wound is immediately repaired. Two more steps, which are clot retraction and platelet inhibition, were included to complete the process and wound repair was incorporated as a sixth step (Berridge, 2012).
Nowadays, since the demand for platelet transfusion continues to grow, extending their storage time to be more than 5 days would be quite beneficial. The short storage time of platelets creates a problem in their availability and inventory. However, if platelets could be maintained for 7 days without bacterial contamination, this would be a significant step in increasing the shelf life of platelets. The extremely short storage time of platelets is a major limitation in transfusion medicine; in this review article, therefore, I focus on determining whether platelets can be stored more than 5- days without any negative effects.
FUTURE STORAGE TIME OF PLATELETS (UP TO 7-DAYS)
The storage time of platelets is one of the most crucial studies in immunohematology at present, since storing the platelets for more than 5-days will reflect outstanding advantages to medical health and be a very great advent. Numerous studies have been conducted regarding the storage time of platelets and the function of donor platelets stored for either 7- or 10-days in additive solutions. These studies have usually evaluated the platelets’ function from day to day of storage. In fact, two major advances have made the expansion of platelet storage more feasible, i.e., the formulation of a platelet additive solution that is able to meet the metabolic needs of platelets over storage to be accomplished with plasma, and the development of platelet bags that permit proper gas exchange across the walls of the container (O2 ingress and CO2 egress). Furthermore, the viability and aggregation of platelets should be analyzed to confirm that platelets can be stored up to 7- or 10-days. Using these indicators are not enough to ensure platelet storage for more than 5-days is possible, but also temperature, bacterial contamination, and pH (Concentration of hydrogen) are very important to be measured to save patients’ life.
In addition to these parameters, other tests have been included to essentially monitor the quality of platelet counts. Most studies focused on the extension of platelet storage time examine the quality and the safety of platelets after 7-days storage, so using additional indicators, such as PF3, PF4, leukocyte counts, glucose and gas analysis is very important to establish such a study in a specific manner. The platelet large cell ratio (P-LCR), platelet distribution width (PDW), and mean platelet volume (MPV) should also be measured to confirm that the platelets are qualifiable to be stored up to 7 days.
Composol boosts the platelets’ shelf-life to up to 7-days
Platelets are currently stored only in plasma in the United Sates. Synthetic storage media may cause a reduction in the platelet storage lesion, hence facilitating increased storage period. With this idea in mind, many platelet additive solutions have been formulated. Various types of platelets additive solutions (PAS), such as PAS-IIIM (MacroPharma) and Composol (Fresenius) in Europe and PlasmaLyte A (Baxter) in the US have been used for platelet storage (Table. 1). These PASs generally contain different combinations and concentrations of acetate, glucose phosphate, and citrate (Gupta et al., 2011; Ohto et al., 2009; Ringwald et al., 2006). These combinations have been found to have both separate and interactive influences on platelet metabolism over storage (Gupta et al., 2011).
;)
Table 1: Composition of various platelet additive solutions. All values in mmol/L; adapted from (Ringwald et al., 2006).
Composol platelet additive solution was utilized to evaluate the in vitro donor platelets’ function stored for 7-days (Gupta et al., 2011). Their study included 30 random blood donors from both genders. The platelet-rich plasma method was used to prepare these donor platelets stored for 7-days at 22 °C in platelet incubators and agitators with and without a composol platelet additive solution. They found out that none of the donor platelet samples displayed bacterial contamination at 22 °C on day 7 with or without composol platelet additive solution. In addition, they reported that the mean platelet count values of all samples observed on day 7 were quite similar. Only one significant difference was observed on day 7 that the probability was less than in the group of platelets without additive solution. In addition, lactate dehydrogenase (LDH) and pH were analyzed and reported that both groups had the most similar values; however, the group of platelets not using the platelet additive solution had a glucose levels with a probability less than 0.001 after 7-days. They also noted a significant decrease of platelet aggregation in a group without additive solution (P < 0.001) on day 7 at 22±°C (Gupta et al., 2011). On comparing the mean values between both groups using some parameters, such as platelet count, PF-3, LDH, glucose, pH, and platelet aggregation, no substantial difference showed in composol although glucose and platelet aggregation exhibited no considerable difference on day 7 at 22 °C without using composol (Gupta et al., 2011).
Using composol in this study was not appropriate at the beginning since it served as a second metabolic power and contained some electrolytes, such as potassium and magnesium that would inhibit the platelet activation and aggregation (Ringwald et al., 2006). They study showed that the levels of LDH were slightly increased on day 7 in both groups but then were maintained. The pH value was decreased on day 7 but then was retained within the normal range recommended by American Association of Blood Bank (AABB). In addition to that, the glucose level and platelet aggregation were slightly lessened in donor platelets with and without additive solution on day 7 at 22°C. It seems regarding the overall results that all parameters were preserved in donor platelets stored for 7-days in composol. Thus, using the composol platelet additive solution is appropriate, and it helps to increase the shelf- life of platelets to 7- days from the current storage (5days).
A recent in vitro study has also performed to compare the quality of PRP over prolonged period of platelet storage in composol (Mokhtar et al., 2016). The study has revealed consistent results with previous studies where most parameters, such as pH and platelet activation rate in composol were within the acceptable limits (Mokhtar et al., 2016). Another recent study was also accomplished using 70% composol to investigate the expression of miR- 16, involved in cell death, in the platelets over a storage period of 7 days (Rajabi et al., 2021). Scientists have demonstrated that platelets with composol showed a significant reduction in the amount of miR-16 compared with platelets without composol (Rajabi et al., 2021). These recent findings should support results from previous studies and make composol additive solution as a good long-term platelet preservative.
Platelet additive solution prevents bacterial contamination
To avoid the bacterial contamination problems and to maintain the functions of platelets to the optimal level, the platelet additive solution should be added. Chandra T and his colleagues collected 150 blood donors of both sexes and stored their platelets in 100% plasma and 20%/80% platelet additive solution. They concentrated their study on extending the shelf life of random donor platelets up to 7 days in the presence or absence of additive solution at different temperatures (22°C, 18°C, and 16°C) comparing the platelet functions stored for 0 and 5 days at 22°C. They analyzed 148 out of 150 samples and discarded 2 samples because of the bacterial contamination on day 7 at 22°C without adding the platelet additive solution. They came out with a significant difference (p<0.001 on day 7 at 16°C without platelet additive solution) in all parameters, including PF-3, platelet count, glucose, LDH, and platelet aggregation (Chandra et al., 2014). In contrast, no meaningful difference on day 7 at 22°C, 18°C, and 16°C with the presence of platelet additive solution was shown in the mean values of some parameters, such as, platelet distribution width (PDW), platelet count, pH, and LDH. However, the levels of mean platelet volume (MPV), glucose, platelet aggregation, and PF 3 demonstrated a major difference on day 7 (p<0.001) at 16°C of the storage period (Chandra et al., 2014). Thus, using a platelet additive solution containing magnesium and potassium (PASIIIM) improves the platelet functions and prevents the bacterial contamination as well as providing a good evidence for changing the guidelines for the increased storage time for platelet concentrates.
2.3 The ability of 7 days storage for pre-storage pooled leukoreduced whole blood-derived platelets
The assessment of pre-storage pooled leukoreduced whole blood-derived platelets stored for up to 7 days was done in vitro (Heddle et al., 2005). They pooled leukoreduced platelets before storage (5units/pool) and then stored them for either 5 or 7 days to find whether they were any significant differences between some parameters in both storages. The main principle they used in their study was whole blood-derived platelets stored for 7- days as a pool to incorporate operational productivities and enabling of bacterial testing and pathogen deactivation. Several samples at the time of pooling either on day 5 or 7 were collected and then tested for biochemical and activation indicators and morphology change. The control samples were also stored separately for 5 or 7 days and subsequently tested (Heddle et al., 2005). They found out that the mean platelet counts were similar. The value of pH was significantly lower with a probability of less than or equal to 0.0001 for the pre-storage pooled platelets, but the partial pressure of O2 (pO2) and lactate were considerably higher with probability of less than or equal to 0.003 on day 5. On the other hand, some parameters, such as hypotonic shock, pCO2, and pH, were decreased with the pre- storage pooled platelets; however, higher values were shown in others, such as pO2, lactate, and morphology scores with probability of less than 0.03. It seems that even though some considerable differences were reported during this study, the significance of the difference would not be anticipated to alter the transfusion’s results. These results demonstrate that the pre-storage pooled leukoreduced whole blood- derived platelets can be stored for up to 7 days; still, more studies should be conducted to ensure that the clinical benefit of platelets stored in a pool is more effective to those stored individually.
Platelet additive solution maintains the morphology and function of platelets for 7 days
Morphological and functional changes should be recorded for donor platelets to evolve the storage time to 7-days. The evaluation of platelet morphology and function in 50 blood donor platelets stored for 7 days with and without platelet additive solution has been reported (Chandra T, 2011). They used the platelet-rich plasma (PRP) method to prepare theses 50 samples. The blood from 50 blood donors was stored in 100% plasma and 20:80 platelet additive solutions. The random donor platelets were placed in an incubator with continuous agitation at 70 cycles/minutes during their storage at room temperature (22°C). They collected the whole blood in anticoagulant Citrate Phosphate Dextrose Adenine (CPDA). The platelet additive solution they used contains 5.02gm sodium gluconate, 5.26gm sodium chloride, 0.373gm potassium chloride, 2.22gm sodium acetate anhydrous, 0.305gm magnesium chloride hexahydrate, and 3.213gm sodium citrate. They discarded two samples because of bacterial contamination. Thus, only 48 out of 50 samples were analyzed. No important difference was shown on day 7 of storage for the mean values of MPV and platelet count in both groups in the presence and absence of platelet additive solution. Also, no substantial difference was noticed in PDW on day 7 in PAS, but there was a significant difference in PDW on day 7 of the storage period (P<0.001) in plasma. The mean values of concentration of hydrogen and LDH showed no considerable difference on day 7 in both groups (with and without platelet additive solution). The platelets stored in platelet additive solution showed a significant difference at day 7, due to the fact that glucose levels and PDW remained as stable as day 1. In contrast, platelets stored in plasma showed deterioration in glucose level and PDW by day 7. They also assessed the platelet aggregation percent (5^M ADP) and found that the platelet aggregation showed a rarely significant difference in plasma, but absolutely no significant difference in platelet additive solution on day 7 at room temperature (22°C) (Chandra T, 2011).
It appears that platelets stored in plasma showed a greater increase in the MPV and PDW on day 7; compared to those platelets stored in additive solution, which showed a slight increase in both these parameters. It is also obvious from this study that the platelet morphology and function can be kept unchanged on day 7 if a platelet additive solution is used. Other parameters, such as glucose and pH can be better retained in platelet additive solution on day 7 as compared to platelets stored in plasma. Consequently, the extended storage time of platelet to 7 days becomes feasible if platelet additive solution is included in the platelets’ storage bag.
Achievement of platelet efficacy in an autologous platelet transfusion stored for 7 days
As many studies have been established, the chance of extending the storage time of platelets up to 7 days is achievable. The survival and recovery of platelets stored for the same duration of time (7days) were measured (Dumont et al., 2002). Bacterial screening tests were the main parameter to be examined in their study to reduce the morbidity and mortality problem associated with prolonged storage of platelets. Consequently, platelet viability becomes the fundamental determinate of reasonable storage time. They assessed the efficacy of platelets stored in plasma for 7 days in 24 single-donor platelets. 51Cr was used to alternately label platelets on days 5 and 7 of storage. The survival and recovery in an autologous platelet transfusion were readily and rapidly determined. The outcomes of pH either in vitro or in vivo were not affected since the pH was kept in the range of 6.2 to 7.61 through 7 days at room temperature (22°C). They found that the characteristics of platelets were properly retained during the storage time (7days) in vitro. In addition, they reported a significant result that Day 5 platelets had better recovery and survival than Day 7 platelets. Even though they recorded declines in recovery and survival in an autologous platelet transfusion, these changes are doubtful to be clinically significant. Thus, platelets can be stored for 7 days by using bacterial screening methods to pick out dirty components devoid of a considerable influence on platelet efficacy as compared to 5-day components.
Apheresis platelets can be stored for 7 days in vitro
The significant difference of apheresis platelets stored for 5- and 7-days was reached (Dumont & VandenBroeke, 2003). The appropriate platelet content limits for apheresis platelets stored for 7 days was identified in a platelet bag using COBE ELP, Gambro BCT (Dumont & VandenBroeke, 2003). The controlled concentration of apheresis platelets and the volume per bag were stored in non-additive solution up to 7 days at room temperature (22°C) with a horizontal agitation. The 24 samples they collected for the study were routinely evaluated in vitro and the consumption of oxygen was measured with a Clark-type electrode, which calculates O2 on a catalytic platinum surface utilizing the net reaction (O2 + 4 e- + 2 H2O ^ 4 OH-) (Clark et al., 1953). They cultured all samples in aerobic medium on Day 7.
The considerable result they found was that no bacterial contamination reported after evaluating 24 samples in storage configurations. Only one sample had a pH value of below 6.0 at room temperature prior to Day 5, while the remaining 23 samples had a pH value above 6.2; however, a pH value of greater than 7.4 was reported at some point in storage for 13 of 23 units without recording any defects in platelet function and activation. They also maintained aerobic metabolic function over 7 days with oxygen consumption of 321 ^mol/h/1012 platelets on Day 7. There was a continuing decrease in platelet in vitro characteristics of storage further than 5 days, but apheresis platelets in vitro could be stored for 7 days (Dumont & VandenBroeke, 2003). The apheresis platelets in non-additive solution stored 100 to 400 ml/bag, 1.0 x 106 platelets ^L, and a max of 5.1 x 1011 platelets/bag could not preserve platelets characteristics during the storage time of 7 days in vitro. Therefore, the extended apheresis platelet storage is dependent on the storage bag composition, storage in a storage solution, and collection method.
The role of pathogen reduction technology (PRT)
Pathogen reduction technology is a very pivotal approach to decrease the pathogen contamination and improve platelet transfusion safety (Lu & Fung, 2020). The methods of RPT are numerous and have different mode of action that are responsible to have the pathogens efficiently reduced (Marschner & Dimberg, 2019). Even though RPT would be very vital to be recruited to investigate the bacterial and infection contamination in long-period storage platelets, none of the studies mentioned in this review used this technique. It seems that the important reason beyond that is to normally evaluate the bacterial contamination in platelets stored for more than 5 days. However, other crucial parameters, such as pH and LDH were measured in all studies and demonstrated values within acceptable ranges, which indicated a less pathogen contamination. It also showed in a recent study that the using RPT might alter the platelets’ bioactivity which in turns affecting the function of platelets (Diallo et al., 2020). Thus, nonfunctional platelets are not suitable to be transfused into a needed patient.
The approved of 7-day platelet shelf life in certain countries
The extended of the platelet shelf life to 7 days is not unnecessary, but bacterial contamination is one of the big concerns to make this task achieved. The health professionals in Australia have approved to store platelets at room temperature for up to 7 days. However, they command the screening of the presence of bacterial commination via accomplishing a large volume delayed sampling (LVDS) strategy. The strategy is usually performed by taking a larger volume of sample at a later day of storge. Thus, detection of bacterial contamination was very low which in turns aiding them to safely extend the storge period from 5 to 7 days (Lifeblood, 2021). Other countries, such as New Zealand, Holland, Canada, and United Kingdom which use the strategy of pathogen reduction technology (PRT) have successfully achieved 7- day platelets with high quality and efficiency (Lifeblood, 2021). In addition to that, the blood services in the United States of America have recently received an approved from the food and drug administration (FDA) to implement 7- day platelets (Holtkamp, 2019). Therefore, the change of storage period to up to 7 days should become essential to be applied in many blood bank laboratories around the world since it ought to provide an improved service to patients by expanding the useable shelf-life and decreasing component waste because of the expiration (Aubron et al., 2018).
The concern of platelet’s storage lesion
It is crucial to understand how well 7-day storage platelets will function clinically whether platelet storage is routinely prolonged over 5 days. It is identified that platelet function decreases over time, the well-known “platelet storage lesion” (Arnason & Sigurjonsson, 2017; Devine & Serrano, 2010; Holme, 1998; Shrivastava, 2009). Most results point to impairment incurred during platelet storage have been taken from some radiolabeled studies in autologous random donor platelets. Accordingly, most these results have shown that platelets transfused following storage have a decline in survival and recovery relative to fresh platelets (Kaufman, 2006; van der Meer & de Korte, 2018; Vit et al., 2020). For example, comparing day 5 and 7 platelets has been observed; consequently, platelets stored for 5 days were found to have recovery of 63% and survival of 160.8 hours, yet platelets stored for 7 days were found to have recovery of 53.9% and survival of 133.6 hours (Slichter et al., 2010). Moreover, there are numerous morphological, biochemical, and functional derangements arise over the storage of platelets (Sandgren & Saeed, 2011). For instance, the accumulation of lactate and the levels of pH decline during platelet storage time (Doescher & Muller, 2013; Gulliksson et al., 2012; Sandgren & Saeed, 2011). The platelets’ shape also converts from discoid into spherical and the platelet aggregation responses to a few agonists decline insignificantly over platelet storage time (Meledeo et al., 2019). Additionally, although storing platelets for 7 days remains metabolically active, several variations in function, structure, and viability/apoptosis between the time of blood collection and transfusion have been reported (Kakali Ghoshal & Maitree Bhattacharyya, 2014a; Heber & Volf, 2015; Ohto et al., 2009; Vucic et al., 2018).
DISCUSSION
Even though the changes of some parameters take place during 7-days storage, extension of platelets storage time up to 7 days is feasible because these changes do not directly affect the platelet characteristics. It is true that the levels of pH and LDH decrease during storage time (7days), but their low levels do not impact on the metabolism and function of platelets. It was demonstrated that the lifespan of platelets is not intrinsic to the cell, so platelet viability is better preserved in vitro than in vivo. Using a platelet additive solution is very important to keep the parameters within their normal range during 7-days storage. It was confirmed by Chandra et al that platelet additive solutions helped to avoid the problem of bacterial contamination.
Moreover, although most platelet additive solutions, such as composol contain potassium and magnesium (Gulliksson, 2014) that inhibit the platelet activation and aggregation, their presences are important during 7-days storage (Wildt-Eggen et al., 2002). In fact, the presence of potassium is very important to maintain the platelet membrane potential (Choi & Hahn, 2010; Ishikawa & Sasakawa, 1987; MAHAUT- SMITH, 2012; Udensi & Tchounwou, 2017). Magnesium causes a decline in platelet activation and impacts the calcium influx into the platelets, but it should be present over the storage time since it activates various potassium pumps (Dean, 2010; Hechler et al., 2019; Hwang et al., 1992). All changes in the parameters of platelets stored for 7 days at different temperatures (22°C and 18°C) are not significant and can disappear by using of platelet additive solutions. Bacterial contamination will be minimized or prevented whether platelet additive solutions can be used in further studies.
CONCLUSION
Although some parameters decline, such as pH and LDH, these are implausible to be clinically significant. Hence, extension of storage for 7 days could be achieved with a platelet additive solution, especially composol to maintain the values of parameters. It could be fulfilled with bacterial screening test, such as platelet test
Pan Genera Detection (PGD) system to avoid the problem of contamination without a considerable effect on the platelet efficacy. The declines in the recovery and survival of platelets during 7-days storage were not clinically significant. Regarding platelet functions during the storage period of 7 days, they were well preserved in platelet additive solution as compared to plasma at 18°C, but not at 16°C. In addition, the parameters of arbitrary donor platelets with an expanded shelf-life of 7 days using a platelet additive solution examined in vitro were the best preserved within normal levels at 22°C. Accordingly, increasing the shelf- life of platelet up to 7 days could be, in fact, practiced by using platelet additive solution resulting in no considerable changes in the parameters of platelets at a lower temperature (18°C) and at room temperature (22°C).
CONFLICT OF INTEREST
The author has no conflicts of interest to declare.
REFERENCES
1. Arnason N. A, Sigurjonsson O.E (2017) New strategies to understand platelet storage lesion ISBT Science Series 12 4 496–500
2. Aubron C, Flint A.W. J, Ozier Y, McQuilten Z (2018) Platelet storage duration and its clinical and transfusion outcomes: a systematic review Critical Care 22 1 185
3. Berridge M.J (2012) Cell Signalling Biology doi:10.1042/csb0001001
4. Bhasin T. S, Sharma S, Manjari M, Mannan R, Kansal V, Chandey M, Piplani S (2013) Changes in megakaryocytes in cases of thrombocytopenia:bone marrow aspiration and biopsy analysis Journal of clinical and diagnostic research :JCDR 7 3 473–479
5. Chandra T G. A, Kumar A, Afreen S (2011) Morphological and functional changes in random donor platelets stored for seven days in platelet additive solution International Journal of Blood Transfusion and Immunohematology 1 20–25
6. Chandra T, Gupta A, Kumar A (2014) Extended shelf life of random donor platelets stored for 7 days in platelet additive solution at different temperatures Biomed J 37 4 211–217
7. Choi B. H, Hahn S.J (2010) Kv1.3: a potential pharmacological target for diabetes Acta Pharmacologica Sinica 31 9 1031–1035
8. Clark L. C Jr, Wolf R, Granger D, Taylor Z (1953) Continuous recording of blood oxygen tensions by polarography J Appl Physiol 6 3 189–193
9. Dean W.L (2010) Role of platelet plasma membrane Ca-ATPase in health and disease World journal of biological chemistry 1 9 265–270
10. Devine D. V, Serrano K (2010) The platelet storage lesion Clin Lab Med 30 2 475–487
11. Diallo I, Benmoussa A, Laugier J, Osman A, Hitzler W. E, Provost P (2020) Platelet Pathogen Reduction Technologies Alter the MicroRNA Profile of Platelet- Derived Microparticles [Original Research] Frontiers in Cardiovascular Medicine 7 31
12. Doescher A, Muller T.H (2013) Noninvasive pH Monitoring in Platelet Concentrates Transfusion Medicine and Hemotherapy 40 2 88–92
13. Dumont L. J, AuBuchon J. P, Whitley P, Herschel L. H, Johnson A, McNeil D, Sawyer S, Roger J.C (2002) Seven-day storage of single-donor platelets:recovery and survival in an autologous transfusion study Transfusion 42 7 847–854
14. Dumont L. J, VandenBroeke T (2003) Seven-day storage of apheresis platelets:report of an in vitro study Transfusion 43 2 143–150
15. Ford J (2013) Red blood cell morphology International Journal of Laboratory Hematology 35 3 351–357
16. George J.N 2015, 4-6-2015 Platelets
17. Ghoshal K, Bhattacharyya M (2014) Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis ScientificWorldJournal, 2014 781857
18. Ghoshal K, Bhattacharyya M (2014a Overview of platelet physiology:its hemostatic and nonhemostatic role in disease pathogenesis TheScientificWorldJournal, 2014 781857-781857
19. Ghoshal K, Bhattacharyya M (2014b Overview of Platelet Physiology:Its Hemostatic and Nonhemostatic Role in Disease Pathogenesis The Scientific World Journal, 2014 781857
20. Gulliksson H (2014) Platelet storage media Vox Sang 107 3 205–212
21. Hultenby K (2012) Storage of platelets:effects associated with high platelet content in platelet storage containers Blood transfusion =Trasfusione del sangue 10 2 205–212
22. Gupta A, Chandra T, Kumar A (2011) In vitro function of random donor platelets stored for 7 days in composol platelet additive solution Asian journal of transfusion science 5 2 160–163
23. Gupta S, Konradt C, Corken A, Ware J, Nieswandt B, Di Paola J, Yu M, Wang D, Nieman M. T, Whiteheart S. W, Brass L.F (2020) Hemostasis vs. homeostasis:Platelets are essential for preserving vascular barrier function in the absence of injury or inflammation Proceedings of the National Academy of Sciences 117 39 24316–24325
24. Heber S, Volf I (2015) Effects of Physical (In)activity on Platelet Function BioMed Research International, 2015 165078
25. Hechler B, Dupuis A, Mangin P. H, Gachet C (2019) Platelet preparation for function testing in the laboratory and clinic:Historical and practical aspects Research and Practice in Thrombosis and Haemostasis 3 4 615–625
26. Heddle N, Barty R, Sigouin C, Boye D, Nelson E, Blajchman M. A, Kelton J (2005) In vitro evaluation of prestorage pooled leukoreduced whole blood-derived platelets stored for up to 7 days Transfusion 45 904–910
27. Holme S (1998) Storage and quality assessment of platelets Vox Sang 74 Suppl 2 207–216
28. Holtkamp C (2019) The FDA Has Opened the Door for 7-Day Platelet Storage Helmer Scientific
29. Hwang D. L, Yen C. F, Nadler J.L (1992) Effect of extracellular magnesium on platelet activation and intracellular calcium mobilization Am J Hypertens 5 10 700–706
30. Ishikawa Y, Sasakawa S (1987) Membrane potential of stored platelets and its effect on platelet functions Thromb Res 45 3 265–273
31. Kaufman R.M (2006) Platelets: Testing, Dosing and the Storage Lesion—Recent Advances Hematology 2006 1 492–496
32. Laki K (1972) Our ancient heritage in blood clotting and some of its consequences Ann N Y Acad Sci 202 297307
33. Lifeblood A. R. C (2021)
7-day platelet shelf life. Transfusion News
34. Lu W, Fung M (2020) Platelets treated with pathogen reduction technology: current status and future direction F1000Research 9 F1000 Faculty Rev-1040
35. MAHAUT-SMITH M.P (2012) The unique contribution of ion channels to platelet and megakaryocyte function Journal of Thrombosis and Haemostasis 10 9 17221732
36. Marschner S, Dimberg L.Y (2019) Chapter 48 - Pathogen Reduction Technologies. In B. H. Shaz, C. D. Hillyer, &M. Reyes Gil (Eds.),
Transfusion Medicine and Hemostasis (Third Edition) 289293 Elsevier
37. Meledeo M. A, Peltier G. C, McIntosh C. S, Bynum J. A, Cap A.P (2019) Optimizing whole blood storage:hemostatic function of 35-day stored product in CPD, CP2D, and CPDA-1 anticoagulants Transfusion 59 S2 15491559
38. Mokhtar M. B, Hashim H. B, Joshi S.R (2016) Assessment of quality of platelets preserved in plasma and platelet additive solution:A Malaysian experience Asian journal of transfusion science 10 1 84–87
39. Ohto H, Ezuki S, Kanno T, Nollet K.E (2009) Extending platelet storage: safety and quality considerations ISBT Science Series 4 2 266–270
40. Periayah M. H, Halim A. S, Mat Saad A.Z (2017) Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis International journal of hematology-oncology and stem cell research 11 4 319–327
41. Rajabi A, Sharifi Z, Yari F, Deyhim M. R, Jalili M.A (2021) The Effect of Composol Medium on miR-16 Expression during Platelet Storage up to Day 7 at Room Temperature Cell journal 22 4 542–547
https://doi.org/10.22074/cellj.2021.6790
42. Riedl J, Ay C, Pabinger I (2017) Platelets and hemophilia: A review of the literature Thrombosis Research 155 131139
https://doi.org/https://doi.org/10.1016/j.t hromres.2017.05.013
43. Ringwald J, Zimmermann R, Eckstein R (2006) The new generation of platelet additive solution for storage at 22 degrees C:development and current experience Transfus Med Rev 20 2 158–164
https://doi.org/10.1016/j.tmrv.2005.11.00 3
44. Sandgren P, Saeed K (2011) Storage of buffy-coat-derived platelets in additive solution:in vitro effects on platelets of the air bubbles and foam included in the final unit Blood transfusion =Trasfusione del sangue 9 2 182–188
https://doi.org/10.2450/2010.0045-10
45. Shrivastava M (2009) The platelet storage lesion Transfusion and Apheresis Science 41 2 105–113
https://doi.org/https://doi.org/10.1016/j.t ransci.2009.07.002
46. Slichter S. J, Bolgiano D, Corson J, Jones M. K, Christoffel T (2010) Extended storage of platelet-rich plasma-prepared platelet concentrates in plasma or Plasmalyte Transfusion 50 10 2199–2209
https://doi.org/10.1111/j.1537- 2995.2010.02669.x
47. Udensi U. K, Tchounwou P.B (2017) Potassium Homeostasis, Oxidative Stress, and Human Disease International journal of clinical and experimental physiology 4 3 111–122
https://doi.org/10.4103/ijcep.ijcep 43 17
48. van der Meer P. F, de Korte D (2018) Platelet Additive Solutions:A Review of the Latest Developments and Their Clinical Implications Transfusion Medicine and Hemotherapy 45 2 98–102
https://doi.org/10.1159/000487513
49. Vit G, Kluter H, Wuchter P (2020) Platelet storage and functional integrity Journal of Laboratory Medicine 44 5 285293
https://doi.org/doh10.1515/labmed- 2020-0067
50. Vucic M, Stanojkovic Z, Antic A, Vucic J, Pavlovic V (2018) Evaluation of platelet activation in leukocyte-depleted platelet concentrates during storage Bosnian journal of basic medical sciences 18 1 2934
https://doi.org/10.17305/bjbms.2017.232 1
51. Wildt-Eggen J, Schrijver J, Bins M, Gulliksson H (2002) Storage of platelets in additive solutions:effects of magnesium and/or potassium Transfusion 42 76–80
https://doi.org/10.1046/j.1537- 2995.2002.00012.x
52. Yip J, Shen Y, Berndt M. C, Andrews R.K (2005) Primary Platelet Adhesion Receptors IUBMB Life 57 2 103–108
