Transfusion and Apheresis Science 41 (2009) 105–113

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Transfusion and Apheresis Science

journal homepage: www.elsevier .com/ locate/ t ransc i

The platelet storage lesion

Manisha Shrivastava *

Department of Transfusion Medicine, Bhopal Memorial Hospital and Research Centre, Bhopal 462038, MP, India

a r t i c l e i n f o a b s t r a c t

Keywords:Platelet storage lesion (PSL)

Platelet concentrates (PCs)Platelet cytoskeletonApoptosisProteomicsPlatelet additive solution (PAS)

1473-0502/$ - see front matter � 2009 Elsevier Ltddoi:10.1016/j.transci.2009.07.002

* Mobile: +91 9425012342.E-mail address: manishasdr@gmail.com

The continuous increase in the demand for platelet transfusion has necessitated the needto establish standards for determining the quality of platelets during storage. Bacterial con-tamination of platelet products and deleterious changes in structure and function referredto as the platelet storage lesion (PSL), have restricted the platelet shelf life to 5 days. ThePSL and platelet health variables have been well studied and documented. The precise cor-relation between in vitro assays and in vivo platelet recovery and survival is yet to beestablished. This review presents an overview of the current understanding of PSL andthe novel approaches being developed to negate the storage lesion.

� 2009 Elsevier Ltd. All rights reserved.

1. Introduction

With the advent of component therapy, the use ofwhole blood-derived or apheresis platelet concentrates(PCs) has become popular in the last two decades all overthe world. The advances in cancer therapy causing myelo-suppression and the rapid development in transfusionmedicine leading to ease in the availability of PCs hascaused an increased interest to improve platelet quality.The shelf life of PCs that earlier varied from 3 days to5 days and then increased to 7 days due to improvementin platelet storage technology was again reduced to 5 daysafter reports of increasing bacterial sepsis associated withprolonged storage at room temperature. The deteriorationof the quality of platelets stored at 22 �C, a process referredto as the platelet storage lesion (PSL) is also a reason for theshort shelf life. PSL is best defined as the sum of all delete-rious changes leading to progressive damage in plateletstructure and function that arise from the time blood isdrawn from a blood donor to the time platelets are trans-fused to a recipient [1]. The progressive decline in functionaccompanied by morphological changes, PSL, has beendocumented by various studies. Preliminary validationstudies document up to 20% loss of platelet recovery

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through 5 days of storage. A further decline of 17% fromday 5 to day 7 has been observed in the containers cur-rently licensed in the United States of America (USA) [2].General reduction in therapeutic efficacy is associated withwell characterized changes observed in common testsassessing platelet morphology, activation, cell metabo-lism/function, and senescence (apoptosis). Few, but notall of these changes are reversible upon transfusion ofplatelets. Transient derangement of platelet metabolism,which does not increase membrane phosphatidylserineexposure, causes in vitro functional abnormalities thatare fully reversed or stabilized by metabolic rescue. Preli-minary data suggest that such rescued platelets may havenormal posttransfusion recovery and survival [3]. Otherthan the critical role in normal hemostatic process andpreservation of vascular integrity, platelets also participatein clot retraction and wound healing. The effectiveness ofplatelet transfusion therapy is at least partially explainedby the role of endogenous platelets in normal hemostasis.The main determinants of the functional capacity of theseunique blood cells are the structure, composition and theirability to respond to various stimuli. Retention of these in-nate properties during preparation and storage of PCs isone of the prime goals of transfusion medicine practice.The issue of platelet quality during extended storage hasbeen well addressed through studies using a variety ofin vitro measures. However, the precise biochemical

106 M. Shrivastava / Transfusion and Apheresis Science 41 (2009) 105–113

pathways involved in the process have yet to be defined.Elucidation of the PSL remains the definitive obstacle be-fore platelet storage times can be extended. Alternatively,novel substances that have many of the hemostatic proper-ties of intact human platelet are being developed as poten-tial alternatives to standard platelet concentrates [4]. Invitro storage parameters of PCs are affected by a numberof variables such as the type of plastic of storage container,temperature, metabolic fuel availability, respiratory capac-ity (dependent on gas diffusion through the container, agi-tation and platelet content) and type of storage medium(plasma or additive solution) [5]. The characteristics deter-mining successful platelet therapy are mainly affected bytechniques of preparation and storage of this life savingblood component.

Despite the widespread use of platelets in clinical prac-tice certain controversies still exist making it difficult todevelop evidence based guidelines for therapeutic use ofplatelets. The relationship between a patient’s plateletcount and clinically significant bleeding remains partiallyunderstood [6]. In this perspective, this articles aims to re-view the research being carried out to understand the nat-ure of change in structure and function of the plateletsduring storage, the PSL, and its possible role in the declin-ing recovery and survival in vivo (Fig. 1).

2. Platelet kinetics

Circulating platelets are discoid, membrane encapsu-lated cellular fragments, without nucleus, originating

Fig. 1. Platelet storage l

primarily from marrow megakaryocytes. The normal plate-let count ranges from 150,000 to 450,000/lL [7]. The finiteplatelet life span in healthy persons is 9.5 ± 0.6 days andplatelet disappearance is generally linear, primarily reflect-ing platelet senescence [8,9]. Storage of platelets for trans-fusion results in partial activation and some loss ofmetabolic function. Stored platelets gradually lose theirde novo ability to aggregate, and platelet matrix adhesioncapabilities are similarly compromised as measured byin vitro assays [10–12]. Longer the platelets are stored,the shorter their subsequent survival in animal models[13]. Interestingly, despite the functional and survival le-sions of platelet storage, transfused platelets appear in cir-culation and restore hemostasis in patients bleeding fromthrombocytopenia or platelet dysfunction, the clinical fac-tor of the patient being another important determinant[14].

3. Stored platelet health: critical variables

3.1. Storage temperature

The optimum liquid platelet storage temperature is 22–24 �C with continuous gentle agitation. Liquid PCs wereoriginally stored at 4 �C until the late 1960s when it wasdiscovered that products stored at room temperature(22–24 �C) had longer in vivo survival and greater hemo-static efficacy than those stored at the colder temperature[15–17]. After storage at 4 �C for 24 and 72 h, plateletviability drops by 18% and 9%, respectively as compared

esion in nutshell.

Fig. 2. Effect of 18 h of storage at different temperatures on in vivosurvival of radiolabled autologous platelets.

M. Shrivastava / Transfusion and Apheresis Science 41 (2009) 105–113 107

to fresh controls [16]. The exposure of platelet to coldcauses change in morphology from discoid to sphericaland appearance of spiny projections on the surface dueto calcium dependent gelsolin activation and phosphoino-sitides mediated actin polymerization [18–20]. The factthat chilling does not necessarily affect the functioning ofplatelet in vivo but reduces the time period of platelet incirculation is explained by the following fact. PlateletvWf receptor (GPIb) complex form a cluster on chilling thateasily binds to aMb2 integrin receptors on the liver macro-phage thus resulting in rapid clearance from circulation.Chilled platelets bind vWf and function normally in vitroand ex vivo after transfusion into CR3-deficient mice.Therefore, GPIb modification might permit cold plateletstorage [19]. Fig. 2 shows the effect of 18 h storage at var-ious temperatures upon the life of radiolabeled autologousplatelets after reinfusion into healthy volunteers. Thereversibility of cold induced platelets is both time and tem-perature dependent [5].

Some of the investigative strategies for prevention ofchanges in platelet cytoskeleton for extended cold storageare addition of micromolar cytochalasin B, an inhibitor ofnew actin filament assembly and calcium chelators to pre-serve the discoid shapes of chilled and rewarmed platelets;addition of trehalose, a disaccharide used during freeze-drying, and the antifreeze glycoproteins (AFGPs) to reduceplatelet activation that occurs when human platelets arestored in the cold [21,22]. However, the future role ofcold-stored platelets in clinical transfusion practice still re-mains unclear. Similarly the use of cryopreserved plateletsremains limited to a few alloimmunized platelet recipientsdue to issue like logistics, cost and potential side effects ofthrombopoietin.

3.2. Metabolic fuel availability and respiratory capacity

Platelet storage bags with proper oxygen permeabilityare critical for the maintenance of the quality of the storedplatelets as oxygen deficiency leads to anaerobic glycolysiswith resultant accumulation of lactic acid and fall in pH.The other factors that affect the oxygen delivery are totalplatelet concentration, storage containers (volume to

surface area ratio) and continuous platelet agitation. Thevery first bags used for PCs were originally designed forfreezing plasma and were made up of polyvinylchloride(PVC) plasticized with di-(2-ethylhexyl) phthalate (DEHP).These bags could store platelet for 3 days without anyunacceptable drop in pH. Further improvements in thematerial of PC storage bags were made to allow higher oxy-gen permeability and lower rates of pH failure [23–25].Second generation containers currently in use are manu-factured from polyolefin/PVC or plasticized with differentcompounds such as triethyl hexyl trimellitate and butyr-yl-thi-hexyl citrate (BTHC). These containers have almosttwice the oxygen permeability of first generation bagsand the storage life of PCs in these bags is 7 days [26]. Leu-coreduced PCs (LR-PCs) can be stored up to 9 days withgood in vitro parameters depending on the sterilizationin the BTHC bags, whereas, storage of LR-PCs in CLX plasticcontainers for 7 days resulted in reduced recovery and sur-vival and in vitro variables, suggestive of extension of thestorage lesion. However, these differences are unlikely tohave any clinical utility owing to their small magnitude[27,28]. Thus, storage-induced lesions do take place inPCs stored in second generation storage containers too un-der the currently recommended conditions, but how farthese changes are clinically relevant needs to be investi-gated [29].

3.3. Platelet storage agitation

The platelets stored with continuous gentle agitation, ameans of facilitating oxygen utilization, were found to bewith better maintained morphology and in vitro function-ality as compared to platelets stored undisturbed. Agita-tion also helps to reduce the rate of pH fall duringstorage [30]. Rotators are available in a face-over-face (cir-cular) angle of rotation or in a flatbed configuration. How-ever, not all agitators are appropriate to store plateletscollected in certain plastic containers. The method of agita-tion makes a significant difference; a flatbed agitator wasfound to be more effective than a rotatory agitator; verticaland horizontal agitation was found to be equally effective[31]. In another study, platelets stored in polyolefin bagsusing 6-rpm elliptical rotators showed decreased post-transfusion recovery and survival [32]. Agitation is alsoassociated with discharge of cytosolic lactate dehydroge-nase (LDH), suggesting that some degree of platelet lysisoccurs during agitation [33].

4. PSL: changes that occur during collection and storage

These changes begin at the time of blood collection andcontinuously progress during component preparation andstorage. Although the platelets stored over a period of7 days generally remain viable, studies suggest an overallreduction in their therapeutic efficacy that is associatedwith morphological, biochemical and functional changes.The reports have observed the development of abnormalforms, loss of disc shape, decreased mean platelet volume(MPV), increased volume and density heterogeneity,increased release of platelet a-granules and cytosolic

Table 1Assays for quantification and characterization of PSL.

Type of Analysis Method

Routine assays in transfusionpractice

Visual inspectionQualitative swirlingPlatelet countConcentrate volumepH* and leukocyte content

Assays primarily for researchapplication

Platelet morphology Morphology score*

Mean platelet volume (MPV)Extent of shape change (ESC)*

Hypotonic shock response (HSR)*

Metabolic activity pH, pO2, pCO2, HCO3 changesLactate productionGlucose consumptionIntracellular calciumATP/ADP ratio*

Platelet aggregation Spontaneous aggregationResponse to dual agonists

Coagulation Fibrinogen binding

Platelet activation CD62 P-selectin expressionAnnexin V binding

Platelet lysis Supernatant LDH contentLysate vWF:Ag levels

Proteomics Differential gel electrophoresis(DIGE)Isotope-coded affinity tagging(ICAT)Isotope tagging for relativeAbsolute quantitation (iTRAQ)

In vivo assays Corrected count increment (CCI)Bleeding time studiesRadiolabeled survival (Cr-51, In-111)Biotin-labeled survival

* In vitro tests correlating with platelet viability.

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proteins, increased procoagulant activity, and altered gly-coprotein (GP) expression, all of which are characteristicof platelet activation [34–47].

The mechanisms responsible for the PSL are not fullyunderstood but are clearly multifactorial. Development ofthe PSL is in general related to collection technique, storageconditions, and postcollection manipulation [11]. Centrifu-gation can affect platelet function by exposing platelets toshear stress conditions causing the discharge of cytosolicLDH and may also stimulate the platelet release reaction[33]. Certain parameters that indicate the decline in thequality of platelets during storage include, the release ofb-thromboglobulin into the suspending plasma andappearance of P-selectin (CD62P, GMP-140) on the plateletmembrane surface following platelet preparation, both ofwhich are evidences of platelet granule release [42,48];expression of platelet dependent antigens such as P-selec-tin, CD62 and lysome-associated membrane proteins 1 and2 indicate reduced platelet viability [49,50]. Similarly,changes in expression of platelet specific glycoproteinssuch as GPIb and GPIIb/IIIa, occurring during platelet stor-age are directly related to storage and preparation proto-cols and postprocessing manipulation and exposure tohigh-dose ultraviolet-B irradiation have shown significantreduction in surface GPIb [51,52]. Structural changesoccurring in the platelet cytoskeleton surface during stor-age are mainly caused due to the formation of plateletmicrovesicle (PMV) mediated by calpalin, a calcium depen-dent neutral protease that degrades the external plateletmembrane proteins like actin (constituting 15–20% of totalplatelet protein), actin-binding protein (ABP), talin, vincu-lin, gelsolin, tubulin, and myosin heavy chain [53]. Duringstorage, the metabolic activity of platelets and residual leu-kocytes continues to consume nutrients and produceharmful metabolic products. Activated clotting factors, cel-lular debris, and proteolytic enzymes found in the sus-pending plasma can adversely affect platelets. Thesestructural changes to the platelet cytoskeleton and surfacemembrane antigens that occur during storage also appearrelated to poorer in vivo posttransfusion recovery and sur-vival [54]. Recent studies also suggest that apoptosis, a noncaspase mechanism may also play a role in platelet cyto-skeletal changes during storage; however, the role of apop-tosis in PSL is poorly understood [55–58]. It is still a matterof conjecture that whether the enucleated platelet cells canundergo apoptosis which is a genetically programmedmethod. However, certain experimental evidence likesthe expression of phosphatidyl serine (PS) on the plateletmembrane which is typical of nucleated cells points tothe fact that apoptotic machinery might be present in theplatelets. The doubt remains whether platelet retains thememory of ‘‘parental” megakaryocytes for apoptosis orwhether platelet mitochondrial DNA has a major role inboth the apoptotic process and the PSL [56].

4.1. Influence of pH on stored human platelets

Glycolysis during storage at 22 �C results in an in-creased lactate production and a fall in pH [59]. Plateletmorphology begins to change when pH reaches 6.8; thechange in morphology and shape is striking at pH 6.0 with

loss of viability. Similar changes have been observed at pHabove 7.5 [60]. A more recent study concluded that plate-lets stored in 100% additive solution (AS) are able to copewith high and low pH values without a strong deteriora-tion with in 3 days. The effects on in vitro quality measureslike CD62P expression and PS exposure were limited dur-ing first 3 days of storage at all pH values. Platelets storedin 30% plasma–70% AS remained stable for 6 days and aremore capable in dealing with different pH values thanplatelets stored in AS alone. The study suggested that thepH decrease is a result of the PSL and not the cause [61].

5. PSL: evaluation and monitoring

The accuracy of in vitro test in predicting the in vivorecovery and survival of transfused platelets is not satisfac-tory. Although a large number of in vitro tests are availableonly a few like platelet number, concentrate volumes, pHat 5 days, and leukocyte content have been used in transfu-sion practice while the majority of the tests are restrictedto research applications. Many of these supplemental as-says cannot be applied to large-scale platelet production.Table 1 lists the various assays being used to followchanges in platelets with processing and storage.

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The changes in normal discoid morphology of theplatelets to other shape is studied using Kunicki morphol-ogy score, a scoring system that assigns 4 points to discs, 2to spheres, 1 to dendritic forms, and none to balloonedplatelets. Simple reporting of the percentage of discoidforms is another morphological test [62]. Classical lighttransmission aggregometry (LTA) has been regarded as amore objective measure of percentage of discoid platelets[63]. Extent of shape change (ESC) in response to agonist,together with an increase in hypotonic shock response(HSR), are two parameters assessed by light-scatteringtechniques that have proved to be of value in assessingplatelet viability. Both morphology score and HSR are con-sidered to have appropriate sensitivity to platelet changesduring storage [64]. However, all the three approaches ap-pear to correlate somewhat with in vivo recovery and sur-vival only at high or low assay values, but are less reliablefor in-between values. Reduction in MPV during storagecould be either due to membrane loss from dendriticforms or activation or apoptosis resulting in microvesicu-lation [65]. The application of flow cytometry helps toassess the changes on the platelet surface such as GPexpression (GPIb, GPIIb, GPIIIa), the generation of plateletactivation markers (CD40L, CD62P, CD63), and the expo-sure of negatively charged phospholipids as determinedby annexin V binding using very small quantities of sam-ple and in a short period of time. Monitoring of GP expres-sion under stimulation with agonists such as adenosinediphosphate or thrombin revealed reduced responsivenessduring storage [66]. Posttransfusion platelet productefficacy can be evaluated by corrected count increments(CCI), considered a gold standard when accompanied bybleeding time studies. However, due to uncontrolledpatient variables and need of large studies the moreacceptable alternative involves the reinfusion of healthyvolunteers with autologous stored platelets radiolabeledwith chromium-51 or indium-111. Percent recoveryand survival may be calculated by serial assay of postin-jection blood radioactivity. Although in vitro tests haveattempted to predict rapidly and economically the abilityof transfused platelets to circulate, correlation within vivo survival and recovery has been documented onlyin extreme values [67–69].

5.1. Proteomics: emerging tool to identify and monitorchanges during platelet storage

Proteomics has emerged as a powerful tool to identifyand monitor changes during platelet storage and incombination with biochemical and physiological studies,facilitates the development of a sophisticated mechanisticview. Study of cold storage lesions, use of PAS andpathogen inactivation strategies are important areaswhere proteomics could help answer basic researchquestions and be an attractive tool to assess establishedprocesses. Earlier studies in this field were impeded bythe lack of knowledge in the field of sequencing and bio-informatics [70]. Mass spectrophotometry along withdevelopment of quantitative proteomic techniques suchas differential gel electrophoresis (DIGE), isotope-coded

affinity tagging (ICAT), and isotope tagging for relativeand absolute quantitation (iTRAQ) are the main tools inthis field. Although, proteomics analyses identify manystorage-associated protein changes, the main limitationof application of proteomics is the difference in typeand number of proteins identified by various tests, thusrequiring more than one test to acquire adequate data[71]. Besides, variation in individual protein concentration(donor–donor variability) continues to represent animportant limiting factor in the study of the PSL. Applica-tions of proteomic ‘‘fingerprinting” for the purposes ofidentifying factors responsible for declining recovery andsurvival of stored platelets can be separated into thecategories of basic research and process assessment[70]. Proteomics provides an excellent tool to decodecomplex processes by identifying novel platelet-expressedproteins, dissecting mechanisms of signalling or meta-bolic pathways, and analyzing functional changes of theplatelet proteome. However, proteomic techniques arelimited in sensitivity as well as in the dynamic rangeand are especially dependent on the protein separationmethod used. A comprehensive review of the various pro-teomic approaches that provide diagnosis of proteolyticevents and posttranslational modifications related withimproved platelet fitness has been given by Thon et al.Proteomic results can help us to understand plateletbiochemistry and physiology and thus unravel mecha-nisms of PSL in time and space for more successfulplatelet transfusion therapy [71].

5.2. Correlation between in vitro platelet assays and in vivorecovery and survival

The quest for a simple in vitro test that will evaluate thein vivo function, quantitative recovery, and survival oftransfused stored platelets remains one of the vitalrequirements of transfusion medicine also being referredto as one of the ‘‘Holy Grails” in transfusion medicine[72]. Unfortunately, in vitro approaches are not reliableindicators of in vivo performance of the allogeneic plate-lets after transfusion. Only a few tests, like, low pH andretention of discoid shape have shown to correlate within vivo recovery [35]. Although the clinical condition ofthe patient also plays an important role in determiningthe final outcome of platelet transfusion, the availabilityof simple rapid, inexpensive and readily interpretable,reproducible test will go a long way in standardizing thetreatment procedure using PCs [3]. The use of non invasiveassessment of platelet shape and concentration (NAPSAC)has shown that percent discoid platelets are not a reliableindicator of posttransfusion platelet recovery [73]. Themethods of preparation of PCs have a huge effect onrecovery and survival characteristics of platelets andwell-designed randomized clinical trials are needed toestablish the relative clinical efficacy of the plateletproducts for bleeding prevention and treatment [74]. Inpractice, in vitro tests are used to initially assess plateletpreparations, but licensing of any new platelet productcurrently requires in vivo survival studies in autologousvolunteers [75].

Table 2Composition of selected platelet additive solutions.

Element (mM) PAS-II PAS-III PAS-IIIM Composol GASP-BIC PlasmaLyte-A

Sodium chloride 115.5 77.3 69.3 90.0 110.0 90Potassium chloride – – 5.0 5.0 5.0 5Magnesium chloride – – 1.5 1.5 3.0 3Citric acid – – – – 7.5 –Na citrate 10.0 10.8 10.8 11.0 – –Na acetate 30.0 32.5 32.5 27.0 15.0 27Na bicarbonate – – – – 26.4 –Na gluconate – – – 23.0 – 23Na phosphate – 28.2 28.2 – 4.0 –Glucose – – – – 30.0 –

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6. Storage of PCs in platelet additive solution (PAS)

The potential of PAS in improving platelet qualityduring storage particularly beyond 5 days has been aninteresting research question over the last decade. Whilein the USA, PAS are still used in research applications, inEurope, the use of synthetic solutions has succeeded inensuring more rationalized blood processing. It has pro-vided greater recovery of plasma for fractionation, contrib-uted to standardization of blood components, besidesbeing part of at least one pathogen reduction process andminimizing the plasma mediated adverse effects like aller-gies and transfusion related acute lung injury (TRALI) [76].Composition of selected PAS is listed in Table 2. Theresearch for the development of better PASs to improveplatelet quality is still under way. Various compounds suchas citrate, acetate, phosphate, potassium, and magnesiumalong with necessary amount of glucose have proved tobe important constituents of PAS. The latest generation ofPASs, the modified PAS-III and Composol-PS, contain mostor all of these compounds [77].

Comprehensive studies done on examining plateletquality in PAS as compared to 100% plasma for storage ofPCs beyond 5 days show that platelets stored in PASII havea higher degree of activation than those stored in plasma[78,79]; where as other additives such as Composol ormodified PAS-III produce in vitro results that are morecomparable to storage to plasma [80,81]. PAS II and Com-posol have been shown to reduce the ability of plateletsto aggregate in response to adenosine diphosphate (ADP)and this defect is only partly reversible [82]. The qualityof platelets during storage in PAS is also influenced bythe type of platelet storage bag, particularly beyond 5 days[83,84] and this effect was studied by assessing the in vitroquality of platelets stored either in 100% plasma, 70% PASIIor 70% Composol in combination with three differentstorage bags. These result show that the type of additivesolution and storage bag in combination affect the mainte-nance of platelet function in vitro during extended storageof PCs. However, the performance of PASII was poorer thanother PAS irrespective of the type of bags [85]. Alteration ofviscosity of PAS may improve platelet quality with betterplatelet recovery [86]. The other factors that have im-proved the in vitro characteristics of platelet include pro-cessing conditions, PAS: plasma ratio and storage pack[34]. The studies examining relationship between PASand platelet efficacy in vivo are still fewer. The recovery

and survival of PCs stored in PASII has been studied incomparison to plasma and in PASII alone. As compared toplasma the recovery and survival of PCs in PASII is reducedby 40% and 20%, respectively [87], whereas another studydone on PCs in PASII but not in plasma, shows acceptablecondition of PCs after 7 days with 80% recovery and 65%survival as compared to day 1 [88]. The transfusion ofPCs stored in PASII in thrombocytopenic patients hasshown varied effects on the CCI, with most studies suggest-ing a reduced CCI [89–91] while some reporting the con-trary [92]. However, with respect to hemostatic scores nodifference was observed in plasma and PASII stored plate-lets after 5 days of storage [90,92]. However, unlike PASII,no significant difference in recovery and survival of PCsstored in plasma or PlasmaLyte was observed in healthyvolunteers after 5 days of storage and beyond 7 days plate-lets stored in PlasmaLyte showed better recovery and sur-vival than PCs stored in plasma [93,94]. Researchers hopethat a number of interesting questions regarding the ef-fects of different compounds in PAS will be answered overthe next few years [95]. Recently published data on thein vitro quality of either buffy coat or apheresis derivedPCs stored in 70% or even 80% of PAS might encouragetransfusion specialists to consider using these PASs in rou-tine blood banking. However, because in vitro tests do notadequately predict clinical effectiveness of platelets aftertransfusion, in vivo studies are still needed to assess thequality of PAS-stored PCs [96,97].

7. Conclusion

The current storage period of 5 days for platelet concen-trates represents a compromise between logistic feasibil-ity, therapeutic efficacy, and recipient safety. Thoughbacterial contamination is the major cause, developmentof PSL at currently recommended storage standards is anequally important reason for reduction in shelf life of thisimportant blood component being used in life threateningsituations to prevent and treat bleeding. A battery ofin vitro measures have been used to study PSL and resultsof on going studies to identify biochemical pathways in-volved in initiation and progression of the process areawaited. Proteomic studies on the PSL with their limita-tions are aiming at understanding the changes occurringwithin the platelet proteome and enabling the design ofbiochemical and physiologic experiments to understand

M. Shrivastava / Transfusion and Apheresis Science 41 (2009) 105–113 111

the meaning of these proteomic findings. A generally poorcorrelation exists between in vitro tests and in vivo animalor human models of platelet function and survival. Thus,more innovative and useful in vitro assays are needed thatmore reliably predict in vivo platelet recovery, survival,and function. Studies are also underway aimed at betterpreserving viability and function of PCs and to unravelthe correlations and mystery of platelet behavior onin vitro storage and transfusion. PAS remains an importantfuture tool for reducing the concurrent infusion of plasmaalong with therapeutic doses of platelets. Other ap-proaches being developed to try to overcome the deleteri-ous effects of the ‘‘PSL” are novel storage techniques(extended cold storage, cryopreservation) and improve-ment in preparation and processing techniques. Effortsfor further improvement in bacteria detection technologymight in future reverse the shelf life back to 7 days. Manyworkers continue to investigate alternative techniques tostore platelets and explore possible donor derived or syn-thetic platelet substitutes. Since clinicians still rely onplatelet transfusion, for at least the near future, more basicresearch to delineate mechanisms of PSL and correlationwith clinical studies is the need of the hour.

Acknowledgements

Sincere thanks to Nirupama Chattarjee, Ph.D. andPavesh Charokar, PGDCA, for assistance during preparationof the manuscript.

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