Pamela Whitley

Seven-day storage of single-donor platelets: recovery and survival in an autologous transfusion study

BACKGROUND: Bacterial screening may effectively reduce the morbidity and mortality risk associated with extended storage of platelets. Platelet viability then becomes the primary determinant of acceptable storage time. This study evaluates the effectiveness of platelets stored in plasma for 7 days.

Efficacy of apheresis platelets treated with riboflavin and ultraviolet light for pathogen reduction

BACKGROUND: Pathogen reduction technologies for platelet (PLT) components offer a means to address continued viral transmission risks and imperfect bacterial detection systems. The efficacy of apheresis PLTs treated with riboflavin (vitamin B2) plus ultraviolet (UV) light (Mirasol, Navigant Biotechnologies) was investigated in a single‐blind, crossover study in comparison to untreated PLTs.

Platelet Storage Lesions in Second-Generation Containers: Correlation with in vivo Behavior with Storage up to 14 Days

Abstract. The relationship between in vivo behavior and in vitro characteristics of 59 platelet concentrates (PC) stored for up to 14 days in a synthetic medium or in CPDA‐1 plasma was systematically investigated. 25 paired studies (1 study was incomplete) were performed comparing platelets suspended either in the synthetic medium or CPDA‐1 plasma with 5 days (n = 5); 7 days (n = 10); 10 days (n = 5); and 14 days (n = 5) of storage. In addition, 10 control studies were performed with freshly prepared PC (6–24 h) in CPDA‐1 plasma. Both percent recovery and survival estimations showed decreases with increasing storage duration, irrespective of storage medium used. In both media, with prolonged storage, the platelet survival curves not only became shorter, but also increasingly exponential, suggesting that in vitro storage caused progressive damage to the platelets present in circulation. Survival curves of platelets suspended in synthetic medium remained more linear, indicative of less random damage during storage. Mean population lifespan (MPL) of the stored PC was determined by the area below the survival curve divided by the mean percent recovery for the fresh PC, which was 55%. MPL decreased from 4.5 days (fresh PC) to 0.4 days after 14 days of storage in plasma, with a 50% reduction (t½) estimated at 7.2 days of storage. MPL t½ for PC stored in the synthetic medium was estimated to be 8.8 days. The decrease in in vivo viability with prolonged storage was paralleled with loss of energy‐dependent in vitro parameters such as hypotonic shock response, shape change with ADP, and ATP levels, and with increased lactate levels. Although the length of the storage period was shown to be the major factor responsible for the variability in MPL observed in this study, multiple linear‐regression analysis showed also that platelet discoid shape, as measured by the shape change, and lactate production were independent in vitro parameters with significant predictability of the in vivo viability. Combined with days of storage in the regression equation, these parameters were found to ‘explain’ 78% of the variability of the MPL found in this study.

Evaluation of an automated system for the collection of packed RBCs, platelets, and plasma

BACKGROUND: This study evaluated the quality of WBC‐reduced platelets, RBCs, and plasma collected on a new system (Trima, Gambro BCT) designed to automate the collection of all blood components. The study also evaluated donor safety and suitability of these components for transfusion.

Collection of two units of leukoreduced RBCs from a single donation with a portable multiple-component collection system.

BACKGROUND: A portable automated component collection system that produces double (2) units of leukoreduced RBCs (DRBCs) from a single donation was evaluated. This study analyzed quality of the collected and final products, the efficacy of automated leukoreduction, and donor safety.

Additive solution‐7 reduces the red blood cell cold storage lesion

Transfusion of long‐stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC “storage lesion” is a major challenge in transfusion medicine. Additive solution‐7 (AS‐7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity.

Properties of platelet concentrates prepared after extended whole blood holding time

Extension of the maximum holding time for whole blood collected into a CPD‐ADSOL system from 6 to 8 hours at ambient temperature under conditions that cause the temperature of the blood to decrease to 20 to 24° C would facilitate the preparation of platelet concentrates (PCs). In this study, the properties of CPD‐PCs prepared and stored for 5 days in PL‐732 containers after various initial holding periods were assessed in two laboratories, designated Laboratory A and Laboratory B. Laboratory A found higher platelet‐rich plasma (PRP) volumes (276 ± 25 vs. 249 ± 19 mL) and platelet yields (76 ± 18 vs. 66 ± 18 × 109 platelets) with 8‐hour holds (n = 10) than with 1‐ to 2‐hour holds (n = 10), although only the difference in PRP volumes was significant (p < 0.05). No significant difference was observed in autologous in vivo recovery (54 ± 11 vs. 47 ± 9%) or survival (167 ± 37 vs. 170 ± 25 hrs), as calculated by gamma function using 111In as radiolabel. Laboratory B also found higher PRP volumes (304 ± 31 vs. 279 ± 37 mL) and platelet yields with 8‐hour holds (n = 12) than with a 6‐hour holds (n = 10) (88 ± 26 vs. 77 ± 27 × 109 platelets). No significant differences were found in morphology score, the extent of release of β‐thromboglobulin, the discharge of lactate dehydrogenase, or hypotonic shock response. These studies showed that an 8‐hour preprocessing hold period did not significantly affect in vitro and in vivo properties of PCs after 5 days of storage.

Evaluation of in vivo and in vitro Quality of Apheresis-Collected RBC Stored for 42 Days

Background and Objectives: New technological developments make it possible to collect red blood cells (RBCs) by apheresis, which allows for better product consistency and has the potential for improved RBC quality. The purpose of these studies was to evaluate the quality and consistency of units of RBCs collected by apheresis using the MCS+® machine (Haemonetics Corp., Braintree, Mass., USA). Materials and Methods: Two studies were performed. In study 1 (n = 10), using containers and CP2D/AS-3 solutions from Medsep Corp. (Covina, Calif. USA), one-unit apheresis RBCs were compared to manually collected RBCs in a random crossover design. In study 2 (n = 12), 6 subjects had one unit collected, while the remaining 6 subjects had two units of RBCs collected with comparison to previously manually collected RBCs from the same donors. Haemonetics containers and solutions were used in study 2. Results: Low RBC volume variability was found for the apheresis collections with a standard deviation of only 6 ml difference between actual and target volumes. Combining the data from the two studies (n = 21 pairs), at 42 days of storage, the apheresis units showed slightly lower hemolysis (0.44±0.26 vs. 0.61±0.50%), lower supernatant potassium levels (50±3 vs. 53±3 mEq/l), and improved tolerance to osmotic shock (47±3 vs. 49±3%) as compared to manual units (p < 0.05). There was no statistically significant difference in RBC ATP (3.0±0.6 vs. 2.9±0.5 μmol/g Hb) or in 24-hour percent recoveries (81±6 for apheresis vs. 81±4% for apheresis red cells). Apheresis RBC quality was not affected by the manufacturer (Haemonetics vs. Medsep) of solutions and containers. Conclusions: RBC units collected by apheresis demonstrated low variability in volume of RBC mass collected, and showed similar RBC properties as compared to manually collected RBCs after processing and after 42 days of storage.

Peptide Inhibitor of Complement C1, a Novel Suppressor of Classical Pathway Activation: Mechanistic Studies and Clinical Potential

The classical pathway of complement plays multiple physiological roles including modulating immunological effectors initiated by adaptive immune responses and an essential homeostatic role in the clearance of damaged self-antigens. However, dysregulated classical pathway activation is associated with antibody-initiated, inflammatory diseases processes like cold agglutinin disease, acute intravascular hemolytic transfusion reaction (AIHTR), and acute/hyperacute transplantation rejection. To date, only one putative classical pathway inhibitor, C1 esterase inhibitor (C1-INH), is currently commercially available and its only approved indication is for replacement treatment in hereditary angioedema, which is predominantly a kinin pathway disease. Given the variety of disease conditions in which the classical pathway is implicated, development of therapeutics that specifically inhibits complement initiation represents a major unmet medical need. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement. In vitro studies have demonstrated that these peptide inhibitors of complement C1 (PIC1) bind to the collagen-like region of the initiator molecule of the classical pathway, C1q. PIC1 binding to C1q blocks activation of the associated serine proteases (C1s–C1r–C1r–C1s) and subsequent downstream complement activation. Rational design optimization of PIC1 has resulted in the generation of a highly potent derivative of 15 amino acids. PIC1 inhibits classical pathway mediated complement activation in ABO incompatibility in vitro and inhibiting classical pathway activation in vivo in rats. This review will focus on the pre-clinical development of PIC1 and discuss its potential as a therapeutic in antibody-mediated classical pathway disease, specifically AIHTR.

In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution.

BACKGROUND: Platelets (PLTs) stored in additive solutions (PASs) may reduce the risk of several plasma‐associated adverse transfusion reactions such as allergic reactions and potentially transfusion‐associated lung injury. The objective of this study was to determine the in vitro characteristics and the in vivo radiolabeled recovery and survival of apheresis PLTs (APs) stored in a new PAS and compare the latter to Food and Drug Administration (FDA) criteria.