The platelet storage lesion
Introduction
With the advent of component therapy, the use of whole blood-derived or apheresis platelet concentrates (PCs) has become popular in the last two decades all over the world. The advances in cancer therapy causing myelosuppression and the rapid development in transfusion medicine leading to ease in the availability of PCs has caused an increased interest to improve platelet quality. The shelf life of PCs that earlier varied from 3 days to 5 days and then increased to 7 days due to improvement in platelet storage technology was again reduced to 5 days after reports of increasing bacterial sepsis associated with prolonged storage at room temperature. The deterioration of the quality of platelets stored at 22 °C, a process referred to as the platelet storage lesion (PSL) is also a reason for the short shelf life. PSL is best defined as the sum of all deleterious changes leading to progressive damage in platelet structure and function that arise from the time blood is drawn from a blood donor to the time platelets are transfused to a recipient [1]. The progressive decline in function accompanied by morphological changes, PSL, has been documented by various studies. Preliminary validation studies document up to 20% loss of platelet recovery through 5 days of storage. A further decline of 17% from day 5 to day 7 has been observed in the containers currently licensed in the United States of America (USA) [2]. General reduction in therapeutic efficacy is associated with well characterized changes observed in common tests assessing platelet morphology, activation, cell metabolism/function, and senescence (apoptosis). Few, but not all of these changes are reversible upon transfusion of platelets. Transient derangement of platelet metabolism, which does not increase membrane phosphatidylserine exposure, causes in vitro functional abnormalities that are fully reversed or stabilized by metabolic rescue. Preliminary data suggest that such rescued platelets may have normal posttransfusion recovery and survival [3]. Other than the critical role in normal hemostatic process and preservation of vascular integrity, platelets also participate in clot retraction and wound healing. The effectiveness of platelet transfusion therapy is at least partially explained by the role of endogenous platelets in normal hemostasis. The main determinants of the functional capacity of these unique blood cells are the structure, composition and their ability to respond to various stimuli. Retention of these innate properties during preparation and storage of PCs is one of the prime goals of transfusion medicine practice. The issue of platelet quality during extended storage has been well addressed through studies using a variety of in vitro measures. However, the precise biochemical pathways involved in the process have yet to be defined. Elucidation of the PSL remains the definitive obstacle before platelet storage times can be extended. Alternatively, novel substances that have many of the hemostatic properties of intact human platelet are being developed as potential alternatives to standard platelet concentrates [4]. In vitro storage parameters of PCs are affected by a number of variables such as the type of plastic of storage container, temperature, metabolic fuel availability, respiratory capacity (dependent on gas diffusion through the container, agitation and platelet content) and type of storage medium (plasma or additive solution) [5]. The characteristics determining successful platelet therapy are mainly affected by techniques of preparation and storage of this life saving blood component.
Despite the widespread use of platelets in clinical practice certain controversies still exist making it difficult to develop evidence based guidelines for therapeutic use of platelets. The relationship between a patient’s platelet count and clinically significant bleeding remains partially understood [6]. In this perspective, this articles aims to review the research being carried out to understand the nature of change in structure and function of the platelets during storage, the PSL, and its possible role in the declining recovery and survival in vivo (Fig. 1).
Section snippets
Platelet kinetics
Circulating platelets are discoid, membrane encapsulated cellular fragments, without nucleus, originating primarily from marrow megakaryocytes. The normal platelet count ranges from 150,000 to 450,000/μL [7]. The finite platelet life span in healthy persons is 9.5 ± 0.6 days and platelet disappearance is generally linear, primarily reflecting platelet senescence [8], [9]. Storage of platelets for transfusion results in partial activation and some loss of metabolic function. Stored platelets
Storage temperature
The optimum liquid platelet storage temperature is 22–24 °C with continuous gentle agitation. Liquid PCs were originally stored at 4 °C until the late 1960s when it was discovered that products stored at room temperature (22–24 °C) had longer in vivo survival and greater hemostatic efficacy than those stored at the colder temperature [15], [16], [17]. After storage at 4 °C for 24 and 72 h, platelet viability drops by 18% and 9%, respectively as compared to fresh controls [16]. The exposure of
PSL: changes that occur during collection and storage
These changes begin at the time of blood collection and continuously progress during component preparation and storage. Although the platelets stored over a period of 7 days generally remain viable, studies suggest an overall reduction in their therapeutic efficacy that is associated with morphological, biochemical and functional changes. The reports have observed the development of abnormal forms, loss of disc shape, decreased mean platelet volume (MPV), increased volume and density
PSL: evaluation and monitoring
The accuracy of in vitro test in predicting the in vivo recovery and survival of transfused platelets is not satisfactory. Although a large number of in vitro tests are available only a few like platelet number, concentrate volumes, pH at 5 days, and leukocyte content have been used in transfusion practice while the majority of the tests are restricted to research applications. Many of these supplemental assays cannot be applied to large-scale platelet production. Table 1 lists the various
Storage of PCs in platelet additive solution (PAS)
The potential of PAS in improving platelet quality during storage particularly beyond 5 days has been an interesting research question over the last decade. While in the USA, PAS are still used in research applications, in Europe, the use of synthetic solutions has succeeded in ensuring more rationalized blood processing. It has provided greater recovery of plasma for fractionation, contributed to standardization of blood components, besides being part of at least one pathogen reduction process
Conclusion
The current storage period of 5 days for platelet concentrates represents a compromise between logistic feasibility, therapeutic efficacy, and recipient safety. Though bacterial contamination is the major cause, development of PSL at currently recommended storage standards is an equally important reason for reduction in shelf life of this important blood component being used in life threatening situations to prevent and treat bleeding. A battery of in vitro measures have been used to study PSL
Acknowledgements
Sincere thanks to Nirupama Chattarjee, Ph.D. and Pavesh Charokar, PGDCA, for assistance during preparation of the manuscript.
References (97)
- et al.
Platelets and related products
- et al.
Platelet kinetics in patients with bone marrow hypoplasia: evidence for a fixed platelet requirement
Blood
(1985) - et al.
The platelet storage lesion
Transfus Med Rev
(1997) - et al.
Mechanisms of cold induced platelet actin assembly
J Biol Chem
(2001) - et al.
The internal calcium concentration of human platelets increases during chilling
Biochim Biophys Acta
(1999) - et al.
Mechanism of shape change in chilled human platelets
Blood
(1995) - et al.
Liquid cold storage of platelets: a revitalized possible alternative for limiting bacterial contamination of platelet products
Transfus Med Rev
(1997) - et al.
Concepts about current conditions for the preparation and storage of platelets
Transfus Med Rev
(1991) - et al.
Platelet storage at 22 °C: role of gas transport across plastic containers in maintenance of viability
Blood
(1975) - et al.
Platelet storage at 22 °C: effect of type of agitation on morphology, viability, and function in vitro
Blood
(1978)
Improved storage of platelets for transfusion in a new container
Blood
Aberrant morphology of platelets stored in five day containers
Thromb Res
An essential adjunct to CMI of platelet for quality control during preparation and storage of platelet concentrates
Transfus Apher Sci
Acquired granular pool defect in stored platelets
Blood
Vesiculation of platelets during in vitro aging
Blood
Platelet membrane glycoproteins: alternations during storage of human platelet concentrates
Thromb Res
Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann’s thrombasthenia in whole blood by flow cytometry
Blood
Constitutive death of platelets leading to scavenger receptor-mediated phagocytosis. A caspase-independent cell clearance program
J Biol Chem
Platelet storage lesion and apoptosis: are they related?
Transfus Apher Sci
Platelet apoptosis in stored platelet concentrates and other models
Transfus Apher Sci
Past and future approaches to assess the quality of platelets for transfusion
Transfus Med Rev
A new platelet storage lesion index based on paired samples, without and with EDTA and cell counting: comparison of three types of leukoreduced preparations
Transfus Apher Sci
Platelet function testing during 5-day storage of single and random donor plateletpheresis
Transfus Apher Sci
Introduction of platelet additive solutions in transfusion practice. advantages, disadvantages and benefit for patients
Transfus Clin Biol
The new generation of platelet additive solution for storage at 22 °C: development and current experience
Transfus Med Rev
A multicentre randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma
Blood
Platelet storage media
Transfus Apher Sci
Platelet additive solution: a future perspective
Transfus Clin Biol
Translation of glycoprotein IIIa in stored blood platelets
Transfusion
Preliminary validation of a new standard of efficacy for stored platelets
Transfusion
Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival
Transfusion
Preparation, preservation and storage of platelet concentrates
Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology
J Clin Oncol
The biogenesis of platelets from megakaryocyte proplatelets
J Clin Invest
Thrombokinetics in man
J Clin Invest
Effects of storage time on quantitative and qualitative platelet function after transfusion
Anesthesiology
Platelet adhesion capacity to subendothelial matrix and collagen in a flow model during storage of platelet concentrates for 7 days
Thromb Haemostasis
Survival of fresh human platelets in a rabbit model as traced by flow cytometry
Transfusion
Influence of clinical status on the efficiency of stored platelet transfusion
Br J Haematol
Effect of storage temperature on maintenance of platelet viability-deleterious effect of refrigerated storage
N Engl J Med
Preparation and storage of platelet concentrates. II. Storage variables influencing platelet viability and function
Br J Haematol
Relative hemostatic effectiveness of human platelets stored at 4° and 22 °C
J Lab Clin Med
The clearance mechanism of chilled blood platelets
Cell
Factors influencing changes in pH during storage of platelet concentrates at 20–24 °C
Vox Sang
Five-day storage of platelets in a non-diethylhexyl phthalate-plasticized container
Transfusion
Sterilization methods of platelet storage containers affects in vitro parameters
Vox Sang
In vitro and in vivo evaluation of leukoreduced platelets stored for 7 days in CLX containers
Transfusion
Evaluation of platelet storage lesions in platelet concentrates stored for seven days
Indian J Med Res
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