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View of Blood Product Safety and Quality

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Blood Product Safety and Quality

Dr. Versha Prasad

Assistant Professor, Dept. of Medical Laboratory Technology, University Institute of Health Sciences, C.S.J.M. University Kanpur

Abstract

Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor.

Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma). Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation.

Key words: Platelets, Blood components, Transfusion, Plasma INTRODUCTION

Blood component therapy became the standard of care in transfusion medicine throughout the industrialized world in the latter half of the twentieth century. The widespread adoption and retention of component therapy were driven by innovations in refrigeration, blood bag design, anticoagulant and preservative solution composition, infectious disease testing, and other means of donor screening.1 The traditional trio of blood components are red cell and platelet concentrates and plasma, which may be generated either by the processing of whole blood donations or via apheresis. Whole blood is processed by centrifugation, predominantly by one of two main protocols which generate different intermediates: platelet-rich plasma (PRP) or a buffy coat (BC).2 White blood cells may be removed from blood components through the use of leukoreduction filters, often during blood processing and before storage.3 Blood components require different storage conditions, with plasma being frozen, red cells being refrigerated, and platelets being maintained at ambient room temperature (RT) Blood component therapy remains widely practiced and widely supported for the majority of patients requiring transfusions; however in the trauma setting it has been suggested that whole blood may be superior to component therapy.4

ASSESING THE QUALITY OF TRANSFUSED PLASMA

Plasma is the liquid portion of an anticoagulated blood donation. Ideally, transfusable plasma would be manufactured under controlled conditions and assayed, prior to its release, for in vitro activities known to correlate with efficacy in each of its clinical indications. The first aspect has been consistently achieved, with impeccable control readily demonstrated by manufacturers. However, with respect to the second aspect, that of quality testing, there is currently no single test or combination of tests established to correlate with clinical efficacy of transfusable plasma. Moreover,

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quality testing is typically done on a portion of units selected from inventory during the product’s shelf-life; prerelease testing is currently done only for transmissible disease screening.5 Investigational quality assessment has evolved beyond the simple determination of regulated coagulation factor activities, towards the assessment of as many coagulation-related protein activities as is feasible, and some work has also been done on global assays of coagulation such as thrombin generation and viscoelastic testing.

INDICATIONS OF PLASMA TRANSFUSION

Most recommendations from national or professional bodies indicate therapeutic plasma transfusion for the correction of clotting factor deficiencies in patients who are bleeding or prophylactic transfusion for those judged to be at risk of bleeding.6 The deficiencies may be of single clotting factors for which no appropriate concentrate is available to the treating physician, or of two or more clotting factors, in the setting of disseminated intravascular coagulation (DIC), vitamin K antagonist reversal, liver disease, cardiopulmonary bypass (CPB), or massive transfusion. Plasma transfusion, or more specifically plasma exchange (PEX), is also indicated in the treatment of thrombotic thrombocytopenic purpura (TTP).

Most indications for plasma transfusion are tied to coagulopathy, defined by Hunt as ―a condition in which the blood’s ability to clot is impaired. Providing plasma by transfusion to remedy coagulopathy is biologically plausible, given that plasma contains all of the soluble coagulation factors, with the caveat that platelets and red cells also contribute to hemostasis, the balanced state in which blood loss from injury is quickly stemmed by clotting.7 For plasma proteins for which no purified concentrate is available (e.g., Factor V or Protein S), transfusable plasma is the only replacement source available to the clinician treating such hereditary or acquired single factor deficiencies. In DIC and CPB, coagulation factor consumption and/or bypass pump fluid management procedures reduce circulating levels of multiple coagulation factors. Vitamin K antagonists such as warfarin reduce the plasma concentration of functional factors (F) II, VII, IX, and X (FII, FVII, FIX, FX) and Proteins C and S, all of which can be found in greater concentration in donor plasma than that of the warfarinized patient, if the pharmacotherapy needs to be rapidly reversed. As the liver is the site of synthesis of most coagulation factors and most coagulation inhibitors, plasma transfusion seems logical to assist the bleeding patient with liver disease, unless hemostasis has been rebalanced. In massive transfusion, usually defined based on the number of red cell units transfused, it is hard to envisage clinical care specialists being able to establish hemostasis without the provision of the coagulation factors found in plasma. Nevertheless, plasma is a relatively dilute source of many coagulation factors that can only be administered relatively slowly, and biological plausibility is no substitute for high-level clinical evidence to guide physician practice.

COAGULATION RELATED PROTEIN IN PLASMA

Proteomics has demonstrated that human plasma contains thousands of different proteins, present over a range of concentration spanning 10–12 orders of magnitude.8,9 Coagulation-related proteins include fibrinogen and coagulation factors II (prothrombin), V, VII, VIII, X, XI, XII, and XIII, as well as von Willebrand Factor (VWF). ADAMTS13 is also of special interest due to its role in TTP. Major coagulation inhibitors include Proteins C and S, antithrombin, alpha-1-antitrypsin, and C1-esterase inhibitor. Among the fibrinolytic proteins, plasminogen and alpha-2-antiplasmin are the most abundant. Most of these proteins demonstrate a wide normal range in healthy blood donors. Reference ranges for coagulation factor activity levels (defined as the 95% confidence limit of the mean ± two SD) were found to vary between the smallest interval of 0.65–1.3 IU/mL for prothrombin and the largest interval of 0.40–1.9 IU/mL for FXII, in a study of over 400 normal men and women .10

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MEASURES OF PLASMA QUALITY

Plasma quality is currently assessed in vitro, using coagulation factor and coagulation-related protein assays. Investigators have employed single factor assays, more global hemostasis tests, thrombin generation, or viscoelastic approaches to characterize different forms of plasma.

1. Coagulation Factor Assays

Most investigators addressing plasma quality issues have employed one-stage coagulation tests. In these assays, anticoagulated plasma samples are recalcified in the presence of factor-depleted plasmas, with coagulation being initiated by the addition of either tissue factor and anionic phospholipids (prothrombin time- (PT-) based assay) or a silicate or other negatively charged polymers combined with anionic phospholipids (activated partial thromboplastin time- (APTT-) based assay). The time to form a clot in such assays is then measured, and factor activity levels in the test plasma are correlated to standard plasma sample clotting times. Most investigators in this field employ automated coagulation analyzers.

2. Hemostasis Screening Tests

Two in vitro clotting tests are widely used by hematologists to screen patients for bleeding disorders or to monitor drug therapy: the PT and the APTT.11 These tests use the initiators of coagulation defined above for the coagulation factor assays, but simply on recalcified plasma. Both have also been employed in investigations of plasma quality. However, these tests are typically insensitive to reductions in single coagulation factor activity of less than 50%. The APTT is best suited to the initial investigation of suspected hemophilia or the monitoring of heparin or heparinoid drugs used to counter thrombosis. The PT is best suited to monitoring drugs like warfarin that disrupt vitamin K antagonism and reduce the functionality of vitamin K dependent proteins, for antithrombotic benefit.

The PT has been standardized as the international normalized ratio (INR), which compares patient PT clotting times to the geometric mean of a group of healthy controls of both genders and which includes a factor related to the potency of the tissue factor preparation used to initiate the test. Both APTT and PT may be performed rapidly as they can be completed in less than one minute per sample, but several commentators have noted that the use of these tests to guide transfusion practice constitutes a use for which neither was designed.12

3. Thrombin Generation

The thrombin generation assay (TGA) relies on thrombin cleavage of a fluorogenic substrate to follow changes in thrombin levels in test plasma during a 30- to 60-minute period. It is initiated with either low concentrations of tissue factor for extrinsic pathway activation or negatively charged biopolymers such as ellagic acid or kaolin for intrinsic pathway activation and is accelerated through the inclusion of anionic phospholipids. TGA features a lag phase, a period of increasing thrombin generation, and a period during which the amount of thrombin being generated declines back to baseline. Time to peak, peak thrombin concentration, and endogenous thrombin potential (ETP, the area under the thrombin versus time curve) are typical calculated parameters. For plasma quality determination, the test is performed in plasma rather than whole blood. Although useful for relative within study comparisons, such as before and after manipulations such as pathogen reduction, TGA is currently viewed as being too variable for routine clinical use, a criticism that may have implications for use in plasma quality investigations.13 It is certainly a much more time-consuming test than ―time to clot‖ assays.

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4. Viscoelastic Testing

Viscoelastic testing refers to thromboelastography (TEG) or rotational thromboelastometry (ROTEM) .14 Both technologies record viscoelastic changes during blood or platelet-rich or platelet-poor plasma clotting by following the changes in oscillation of a pin or wire immersed in the test fluid; in TEG the cup is mobile and the pin or wire immobile, while in ROTEM the mobilities are reversed. Either assay can be initiated using kaolin and phospholipids or tissue factor. Test runs can require up to 30 minutes for completion. Both technologies have been used as point-of-care tests to guide hemostatic therapy and have been employed in pivotal trials of fibrinogen concentrates.15

PATHOGEN REDUCED PLASMA

Plasma may also be subjected to additional manipulations designed to increase the considerable protection already afforded to patients by its prerelease immunological and nucleic acid testing for transfusion-transmitted pathogens. These include treatments of pooled plasma with solvent-detergent mixtures and of individual plasma units with agents such as methylene blue or amotosalen, which must be removed prior to infusion after illumination of units with ultraviolet or visible light, or riboflavin (vitamin B2), for which there is no removal requirement.16,17 Quality assessment of these products has been largely limited to comparisons to the FFP from which they are derived. Efficacy determinations have included clinical studies, including those leading to licensure on the basis of similar performance to FFP.

DEHYDRATED PLASMA

Plasma was originally introduced into clinical practice, during World War II, as a lyophilized product appropriate for battlefield use. Such dehydrated plasma formulations attempt to replace conventional plasma with a product that does not require a cold-storage chain and which can be reconstituted more rapidly than frozen plasma can be thawed. Plasma may be dried either in pools (with or without pathogen inactivation) or as single units. The most common approach is freeze-drying, or lyophilization, a process by which plasma is rapidly frozen and maintained at low temperatures under partial vacuum. Sufficient heat is then introduced such that frozen water in the product is driven off via sublimation. An alternative approach involves spray drying, in which atomization and heat are used to evaporate microdispersed water droplets. Both technologies provide stable, reversibly dried products in which >95% of the original water content is removed.

APPROPRIATE USE OF PLASMA TRANSFUSION

The amount of plasma transfused in several countries has declined in recent years, including Canada, the United Kingdom, and the United States .18,19 The decline has been linked to efforts to increase appropriateness of plasma transfusion, to the increased availability of plasma protein products such as PCCs, and to improvements in surgical techniques. It seems likely that this trend will continue, barring new clinical data supporting plasma transfusion.

Although there is disagreement among physicians as to the value of plasma transfusion and some indications are supported by weaker evidence than others, there is reasonable expert consensus as to uses of transfusable plasma which are inappropriate. Multiple audits of transfusable plasma utilization have shown that over 30% of the time, plasma is transfused inappropriately, typically in efforts to alter a mildly elevated INR and to nonbleeding patients .20-23 Although most studies of plasma quality end with an exhortation to trialists to obtain better RCT data, it is likely that improvements in plasma utilization could be achieved more readily by diminishing inappropriate transfusion of plasma.

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FUTURE PROSPECTS FOR QUALITY ASSESSMENT OF TRANSFUSABLE PLASMA An extensive literature exists regarding the effect of different manipulations or process changes on coagulation factor activities in transfusable plasma or its derivatives. However, linking these changes to differences in overall hemostatic function of plasma has not been extensively attempted. Available data using more global tests of hemostasis such as thrombin generation and viscoelastic testing has started to suggest that many of the observed alterations in one or more coagulation factors are not particularly relevant to hemostasis, given its complexity and the number of mechanisms that can combine to adapt to changes in procoagulant and/or anticoagulant protein profiles within the large functional reserve of this biological fluid. If thrombin generation and viscoelastic tests can be better correlated with patient clinical status and adapted to more rapid execution, such assays may supplant coagulation factor assays in the effort to answer the elusive question, ―is this unit of transfusable plasma of high quality?‖

Quality of Platelet Concentrates

PLATELETS: NEW MODES OF STORAGE

Platelet transfusions are essential for the treatment of patients with acute bleeding or hemorrhage and for prevention of bleeding in severe thrombocytopenia.24-26 When the vasculature is damaged, platelets adhere, aggregate, and become activated, eventually forming a platelet plug, as well as providing a catalytic surface for thrombin generation. Platelet concentrates (PCs) for transfusion are typically prepared either from whole blood or by apheresis and are stored at RT (20–24°C) for up to 7 days. The shelf-life of platelets stored at RT is limited due to the risk of bacterial growth and contamination, which can cause life-threatening transfusion-related infections. Additionally, platelets stored at RT gradually deteriorate and undergo a decline in hemostatic and metabolic function, which is known collectively as the platelet storage lesion.27,28

Due to the short shelf-life of PCs, providing platelets to remote, rural, and austere environments is often challenging. Alternative storage modalities such as cryopreservation and cold or refrigerated storage are currently being explored to overcome the challenges associated with the short shelf-life of PCs. It is clear that platelets stored under these conditions appear to be very different from standard, RT-stored platelets, when assessed using in vitro assays previously applied to RT-stored platelets alone.29,30 Further, cryopreservation of platelets is a relatively new field, and while cold storage of platelets has been studied for many decades, there is a renewed interest in this storage mode, and the in vivo efficacy of these novel platelet components is only now being investigated. Standard measures of activation and metabolism are not always sufficient for cold or cryopreserved platelets and generally do not correlate well with in vivo transfusion outcomes. A well-defined panel of assays to measure the in vitro quality of these components has not yet been established. This section of the review will explore the differences between platelets stored frozen, refrigerated, or at RT and will address the techniques that may be most appropriate to measure them in vitro function and quality.

PLATELETS: ALTERNATIVE MODES OF STORAGE

To circumvent problems associated with the short shelf-life of platelets, alternative modes of platelet storage have been investigated. These include platelet cryopreservation, cold storage, and lyophilization. Here we focus on cryopreservation and cold platelet storage, as these are being most actively pursued by several groups. Platelet cryopreservation typically involves addition of DMSO to a final concentration of 4–6% (vol/vol) and storage at −80°C for between 2 and 4 years.31-33 Platelet cryopreservation was pioneered by the US military and later the Netherlands military, who have

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successfully transfused over 1000 cryopreserved platelets during military deployments to Bosnia, Iraq, and Afghanistan.34,35 This technology is now being adopted by many countries. Platelet cryopreservation and the subsequent thawing processes are, however, time consuming and more expensive than standard RT storage, and other alternatives have been sought. One such alternative is cold storage of platelets, which is extremely simple logistically, as such platelet products can be stored in a refrigerator as per red cells and do not require agitation.

Platelet Cryopreservation

Methods used today for platelet cryopreservation were pioneered by Handin and Valeri for the US military and first published in the 1970s. The original protocol described addition of 5 to 6% DMSO to hyperconcentrated platelets prepared from a single unit of whole blood using the PRP method.36,37 The DMSO was not removed prior to freezing, and after thawing the platelets were washed and resuspended in autologous plasma. The platelets were found to be hemostatically effective upon transfusion. Subsequent protocols described removal of DMSO prior to freezing, as this allowed platelets to be thawed and reconstituted immediately after thawing with reduction of DMSO content.

Cold Storage of Platelets

Platelets were stored in the cold (at ~4°C) until 1969, when transfused platelets were shown to be more rapidly cleared from the circulation than platelets stored at RT.38 The majority of platelet transfusions are given prophylactically to thrombocytopenic hematooncology patients.39 As such, a longer lifespan in the circulation is desirable, and cold storage of platelets ceased, with adoption of storage at RT (20–24°C). However, the advantages of cold storage include prolonged shelf-life due to reduced metabolism, enhanced hemostatic activity, improved bacteriologic safety, and ease of storage and transport, as the same infrastructure for storage and transport of red cells could be utilized.

Quality Assessment of Stored Red Cell Concentrates

Transfusion of red blood cell concentrates (RCCs) is a necessary, lifesaving clinical therapy. RCCs are given to increase oxygen delivery to tissues in clinical situations where the circulating red blood cell (RBC) level is low (anemia) due to RBC loss (trauma/surgical hemorrhage), decreased bone marrow production (chemotherapy, aplastic anemias), defective hemoglobin (hemaglobinopathies, thalassemias), or decreased RBC survival (hemolytic anemias).

To ensure that RCCs are produced in a consistent and controlled manner, blood collection agencies routinely test products as part of their quality assurance programmes and as part of their continuous improvement activities prior to making changes to equipment or processes. Acceptable standards for product safety and quality are outlined in government regulations and by standard-setting organizations. Despite these stringent control mechanisms, a great deal of variability still exists within the blood components transfused which may affect patient outcomes. Motivated by a need for more concerted efforts to understand the factors affecting RCC quality, this section will review the changes that occur to RBC during blood banking, current quality testing practices, and the factors which affect the quality of stored RCCs.

The primary function of RBCs is to transport oxygen from the lungs to the body tissues, where the exchange for carbon dioxide is facilitated through the synergistic effects of hemoglobin, carbonic anhydrase, and band 3 protein, followed by carbon dioxide delivery to the lungs for release.

Successful oxygen transport is dependent on the efficacy of three critical elements: the RBC membrane, hemoglobin, and the cellular energetics.

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The RBC membrane is a fluid structure composed of a semipermeable lipid bilayer with an asymmetrically organized mosaic of proteins. Membrane lipids compromise approximately 40% of the RBC membrane mass, with equimolar quantities of unesterified cholesterol and phospholipids, and small amounts of free fatty acids and glycolipids. Membrane proteins comprise approximately 52% of the RBC membrane mass and can be categorized into integral and peripheral proteins according to their location relative to the lipid bilayer.40 Integral membrane proteins, such as glycophorin and band 3 protein, transverse the membrane and function as receptors and transporters.

In contrast, peripheral proteins are only found on the cytoplasmic surface of the membrane and form the RBC cytoskeleton. The major components of the RBC cytoskeleton are spectrin, ankyrin, protein 4.1, actin, and adducin, which form a mesh-like network of microfilaments that strengthens the RBC membrane while maintaining RBC shape and stability.41 The unique characteristics of the RBC membrane and cytoskeleton afford the cells the ability to reversibly deform as they traverse the microvasculature and thereby deliver oxygen from the lungs to the tissues.

The second element that has to be maintained for the cells to function normally is hemoglobin.

Hemoglobin is a conjugated protein consisting of two pairs of globin chains and four heme groups, each containing a protoporphyrin group and an iron molecule in the ferrous form .42 The uptake and release of oxygen by the hemoglobin molecule are controlled by the RBC organic phosphate 2,3- disphosphoglycerate (2,3-DPG), which binds to the cleft between globin chains, resulting in a deoxyhemoglobin conformation that facilitates the release of oxygen. Therefore, increased 2,3-DPG levels triggered by tissue hypoxia will shift the hemoglobin oxygen dissociation curve to the right, increasing oxygen delivery to the tissues.

Maintenance of the RBC membrane system and hemoglobin function is dependent on energy generation through RBC metabolic pathways. There are four major RBC metabolic pathways: the Embden-Mayerhof pathway, in which most RBC adenosine triphosphate (ATP) is generated through the anaerobic breakdown of glucose; the hexose monophosphate shunt, which produces NADPH to protect RBCs from oxidative injury; the Rapoport-Luebering shunt, responsible for the production of 2,3-DPG for the control of hemoglobin oxygen affinity; and finally, the methemoglobin reduction pathway, which reduces ferric heme iron to the ferrous form to prevent hemoglobin denaturation. All four metabolic pathways are critical to RBC function

CONCLUSION

Existing determinants of blood product quality provide some information that is plausibly linked to predicting posttransfusion efficacy of their transfusion. For RCC and platelet concentrates, the evidence for most indications is stronger than that currently available for transfusable plasma.

Nevertheless, controversies persist among transfusionists regarding what constitutes an appropriate transfusion and/or an appropriate dose of the blood product, in different clinical settings. Emerging tests offer potential improvements in strengthening the linkages between pretransfusion quality assessments and posttransfusion clinical efficacy and in determining which blood products are indeed of the highest quality. It must be remembered that blood products, unlike traditional pharmaceutical agents, are complex, multicomponent products. Improved characterization and quality assessment have an important role to play in furthering our understanding of how these products, and their modified forms, can best be used to benefit patients. At present there is insufficient evidence to endorse replacing current blood component quality tests with more complicated technologies, such as thrombin generation assays and viscoelastic methodologies for both platelets and plasma, or plethysmography for red cells; nevertheless, it is only through continuing to investigate emerging tests and cross-correlating them with existing measures that the field can improve. The relatively simple

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tests currently employed as quality markers, such as FVIII activity for plasma, pH, and platelet count for platelets, and hemoglobin-related parameters for red cells, remain of value and can be conducted in many settings with locally available instrumentation.

REFRENCES

1. R. C. Arya, G. S. Wander, and P. Gupta, ―Blood component therapy: which, when and how much,‖ Journal of Anaesthesiology Clinical Pharmacology, vol. 27, no. 2, pp. 278–284, 2011.View at: Publisher Site | Google Scholar

2. R. R. Vassallo and S. Murphy, ―A critical comparison of platelet preparation methods,‖ Current Opinion in Hematology, vol. 13, no. 5, pp. 323–330, 2006.View at: Publisher Site | Google Scholar

3. M. A. Blajchman, ―The clinical benefits of the leukoreduction of blood products,‖ Journal of Trauma—Injury, Infection and Critical Care, vol. 60, no. 6, pp. S83–S88, 2006.View at: Publisher Site | Google Scholar

4. M. D. Zielinski, D. H. Jenkins, J. D. Hughes, K. S. W. Badjie, and J. R. Stubbs, ―Back to the future: the renaissance of whole-blood transfusions for massively hemorrhaging patients,‖ Surgery (United States), vol. 155, no. 5, pp. 883–886, 2014.View at: Publisher Site | Google Scholar

5. S. F. O'Brien, Q.-L. Yi, W. Fan, V. Scalia, M. A. Fearon, and J.-P. Allain, ―Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services,‖ Vox Sanguinis, vol.

103, no. 1, pp. 83–86, 2012.View at: Publisher Site | Google Scholar

6. E. S. Cooper, A. W. Bracey, A. E. Horvath, J. N. Shanberge, T. L. Simon, and D. H. Yawn,

―Practice parameter for the use of fresh-frozen plasma, cryoprecipitate, and platelets. Fresh- Frozen Plasma, Cryoprecipitate, and Platelets Administration Practice Guidelines Development Task Force of the College of American Pathologists,‖ The Journal of the American Medical Association, vol. 271, no. 10, pp. 777–781, 1994.View at: Publisher Site | Google Scholar

7. ―Guidelines for red blood cell and plasma transfusion for adults and children,‖ Canadian Medical Association Journal, vol. 156, no. 11, supplement, pp. S1–S24, 1997.View at: Google Scholar

8. A. Kovács and A. Guttman, ―Medicinal chemistry meets proteomics: fractionation of the human plasma proteome,‖ Current Medicinal Chemistry, vol. 20, no. 4, pp. 483–490, 2013.View at: Google Scholar

9. R. Pieper, C. L. Gatlin, A. J. Makusky et al., ―The human serum proteome: display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins,‖ Proteomics, vol. 3, no. 7, pp. 1345–1364, 2003.View at: Publisher Site | Google Scholar

10. E. J. Favaloro, S. Soltani, J. McDonald, E. Grezchnik, and L. Easton, ―Cross-laboratory audit of normal reference ranges and assessment of ABO blood group, gender and age on detected levels of plasma coagulation factors,‖ Blood Coagulation and Fibrinolysis, vol. 16, no. 8, pp.

597–605, 2005.View at: Publisher Site | Google Scholar

(9)

11. A. H. Kamal, A. Tefferi, and R. K. Pruthi, ―How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults,‖ Mayo Clinic Proceedings, vol. 82, no. 7, pp. 864–873, 2007.View at: Publisher Site | Google Scholar

12. J. B. Segal and W. H. Dzik, ―Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review,‖ Transfusion, vol. 45, no. 9, pp. 1413–1425, 2005.View at: Publisher Site | Google Scholar

13. M. D. Lancé, ―A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis,‖ Thrombosis Journal, vol. 13, article 1, 2015.View at: Publisher Site | Google Scholar

14. G. A. Hans and M. W. Besser, ―The place of viscoelastic testing in clinical practice,‖ British Journal of Haematology, vol. 173, no. 1, pp. 37–48, 2016.View at: Publisher Site | Google Scholar

15. C. Solomon, L. M. Asmis, and D. R. Spahn, ―Is viscoelastic coagulation monitoring with ROTEM or TEG validated?‖ Scandinavian Journal of Clinical and Laboratory Investigation, vol. 76, no. 6, pp. 503–507, 2016.View at: Publisher Site | Google Scholar

16. P. Hellstern, ―Solvent/detergent-treated plasma: composition, efficacy, and safety,‖ Current Opinion in Hematology, vol. 11, no. 5, pp. 346–350, 2004.View at: Publisher Site | Google Scholar

17. P. F. Lindholm, K. Annen, and G. Ramsey, ―Approaches to minimize infection risk in blood banking and transfusion practice,‖ Infectious Disorders—Drug Targets, vol. 11, no. 1, pp. 45–

56, 2011.View at: Publisher Site | Google Scholar

18. M. P. Zeller, K. S. Al-Habsi, M. Golder, G. M. Walsh, and W. P. Sheffield, ―Plasma and plasma protein product transfusion: a canadian blood services centre for innovation symposium,‖ Transfusion Medicine Reviews, vol. 29, no. 3, pp. 181–194, 2015.View at: Publisher Site | Google Scholar

19. B. Whitaker, S. Rajbhandary, S. Kleinman, A. Harris, and N. Kamani, ―Trends in United States blood collection and transfusion: results from the 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey,‖ Transfusion, vol. 56, no. 9, pp. 2173–

2183, 2016.View at: Publisher Site | Google Scholar

20. A. Tinmouth, T. Thompson, D. M. Arnold et al., ―Utilization of frozen plasma in Ontario: a provincewide audit reveals a high rate of inappropriate transfusions,‖ Transfusion, vol. 53, no.

10, pp. 2222–2229, 2013.View at: Publisher Site | Google Scholar

21. A. W. Shih, E. Kolesar, S. Ning, N. Manning, D. M. Arnold, and M. A. Crowther,

―Evaluation of the appropriateness of frozen plasma usage after introduction of prothrombin complex concentrates: A retrospective study,‖ Vox Sanguinis, vol. 108, no. 3, pp. 274–280, 2015.View at: Publisher Site | Google Scholar

22. C.-H. Hui, I. Williams, and K. Davis, ―Clinical audit of the use of fresh-frozen plasma and platelets in a tertiary teaching hospital and the impact of a new transfusion request

(10)

form,‖ Internal Medicine Journal, vol. 35, no. 5, pp. 283–288, 2005.View at: Publisher Site | Google Scholar

23. S. Pybus, A. MacCormac, A. Houghton, V. Martlew, and J. Thachil, ―Inappropriateness of fresh frozen plasma for abnormal coagulation tests,‖ Journal of the Royal College of Physicians of Edinburgh, vol. 42, no. 4, pp. 294–300, 2013.View at: Publisher Site | Google Scholar

24. S. J. Stanworth, L. J. Estcourt, G. Powter et al., ―A no-prophylaxis platelet-transfusion strategy for hematologic cancers,‖ The New England Journal of Medicine, vol. 368, no. 19, pp. 1771–1780, 2013.View at: Publisher Site | Google Scholar

25. R. M. Kaufman, B. Djulbegovic, T. Gernsheimer et al., ―Platelet transfusion: a clinical practice guideline from the AABB,‖ Annals of Internal Medicine, vol. 162, no. 3, pp. 205–

213, 2015.View at: Publisher Site | Google Scholar

26. M. J. Cohen and S. A. Christie, ―New understandings of post injury coagulation and resuscitation,‖ International Journal of Surgery, vol. 33, pp. 242–245, 2016.View at: Publisher Site | Google Scholar

27. B. G. Solheim, O. Flesland, J. Seghatchian, and F. Brosstad, ―Clinical implications of red blood cell and platelet storage lesions: an overview,‖ Transfusion and Apheresis Science, vol.

31, no. 3, pp. 185–189, 2004.View at: Publisher Site | Google Scholar

28. C. Saunders, G. Rowe, K. Wilkins, and P. Collins, ―Impact of glucose and acetate on the characteristics of the platelet storage lesion in platelets suspended in additive solutions with minimal plasma,‖ Vox Sanguinis, vol. 105, no. 1, pp. 1–10, 2013.View at: Publisher Site | Google Scholar

29. L. Johnson, S. Tan, B. Wood, A. Davis, and D. C. Marks, ―Refrigeration and cryopreservation of platelets differentially affect platelet metabolism and function: a comparison with conventional platelet storage conditions,‖ Transfusion, vol. 56, no. 7, pp. 1807–1818, 2016.View at: Publisher Site | Google Scholar

30. L. Johnson, C. P. Coorey, and D. C. Marks, ―The hemostatic activity of cryopreserved platelets is mediated by phosphatidylserine-expressing platelets and platelet microparticles,‖ Transfusion, vol. 54, no. 8, pp. 1917–1926, 2014.View at: Publisher Site | Google Scholar

31. C. R. Valeri, R. Srey, J. P. Lane, and G. Ragno, ―Effect of WBC reduction and storage temperature on PLTs frozen with 6 percent DMSO for as long as 3 years,‖ Transfusion, vol.

43, no. 8, pp. 1162–1167, 2003.View at: Publisher Site | Google Scholar

32. F. Noorman, R. Strelitski, and J. Badloe, ―Frozen platelets can be stored for 4 years at—80°C without affecting in vitro recovery, morphology, receptor expression, or coagulation profile,‖ Transfusion, vol. 54, no. S2, pp. 15A–279A, 2014.View at: Google Scholar

33. P. A. Daly, C. A. Schiffer, J. Aisner, and P. H. Wiernik, ―Successful transfusion of platelets cryopreserved for more than 3 years,‖ Blood, vol. 54, no. 5, pp. 1023–1027, 1979.View at: Google Scholar

(11)

34. C. C. M. Lelkens, J. G. Koning, B. de Kort, I. B. G. Floot, and F. Noorman, ―Experiences with frozen blood products in the Netherlands military,‖ Transfusion and Apheresis Science, vol. 34, no. 3, pp. 289–298, 2006.View at: Publisher Site | Google Scholar

35. J. Badloe and F. Noorman, ―The Netherlands experience with frozen −80°C red cells, plasma and platelets in combat casualty care,‖ Transfusion, vol. 51, no. S3, pp. 1A–297A, 2011.View at: Google Scholar

36. R. I. Handin and C. R. Valeri, ―Improved viability of previously frozen platelets,‖ Blood, vol.

40, no. 4, pp. 509–513, 1972.View at: Google Scholar

37. C. R. Valeri, H. Feingold, and L. D. Marchionni, ―A simple method for freezing human platelets using 6% dimethylsulfoxide and storage at −80°C,‖ Blood, vol. 43, no. 1, pp. 131–

136, 1974.View at: Google Scholar

38. S. Murphy and F. H. Gardner, ―Effect of storage temperature on maintenance of platelet viability—deleterious effect of refrigerated storage,‖ The New England Journal of Medicine, vol. 280, no. 20, pp. 1094–1098, 1969.View at: Publisher Site | Google Scholar

39. A. Charlton, J. Wallis, J. Robertson, D. Watson, A. Iqbal, and H. Tinegate, ―Where did platelets go in 2012? A survey of platelet transfusion practice in the North of England,‖ Transfusion Medicine, vol. 24, no. 4, pp. 213–218, 2014.View at: Publisher Site | Google Scholar

40. N. Mohandas and J. A. Chasis, ―Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids,‖ Seminars in Hematology, vol. 30, no. 3, pp. 171–192, 1993.View at: Google Scholar

41. L. H. Derick, S.-C. Liu, A. H. Chishti, and J. Palek, ―Protein immunolocalization in the spread erythrocyte membrane skeleton,‖ European Journal of Cell Biology, vol. 57, no. 2, pp.

317–320, 1992.View at: Google Scholar

42. S. Peter Klinken, ―Red blood cells,‖ International Journal of Biochemistry and Cell Biology, vol. 34, no. 12, pp. 1513–1518, 2002.View at: Publisher Site | Google Scholar

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