Decreased Hemolysis and Improved Platelet Function in Blood Components Washed With Plasma-Lyte A Compared to 0.9% Sodium Chloride

Refaai, Majed A.; Conley, Grace; Henrichs, Kelly; McRae, Hannah L; Schmidt, Amy E.; Phipps, Richard P.; Spinelli, Sherry L.; Masel, Debra; Cholette, Jill M.; Pietropaoli, Anthony P.; Eaton, Michael P.; Blumberg, Neil

doi:10.1093/ajcp/aqy036

Cited by 18 publications

(10 citation statements)

References 36 publications

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“…These data suggest the buffering capacity provided by the phosphate in citrate‐free PAS‐III may preserve cell viability better than an additive solution lacking phosphate . A recent study has suggested that unbuffered saline strikingly impairs PLT function in vitro, highlighting the importance of pH and cell quality . The fact that storage of PLTs in citrate‐free PAS‐III improves multiple storage parameters, while maintaining adequate pH levels is likely why no spontaneous aggregation was observed throughout the 7‐day storage period under our conditions.…”

Section: Discussionmentioning

confidence: 65%

Sodium citrate contributes to the platelet storage lesion

2019

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BACKGROUND: Sodium citrate has become the preferred anticoagulant used for apheresis collection and has been included in commercial platelet additive solutions (PASs) since PAS-II. It was suggested that citrate be included in PASs to prevent spontaneous aggregation. Reports in cell lines and cord blood have demonstrated that concentrations of citrate present in PAS formulations (10 mM) cause apoptosis. We evaluated whether the removal of citrate from PAS-III could improve platelet storage. STUDY DESIGN AND METHODS: Study 1 evaluatedthe effects of a citrate dose response on the storage of platelets in 65% PAS containing sodium chloride, sodium acetate, and phosphate. Study 2 compared the cell quality and function of platelets stored in 65% citrate-free PAS-III or PAS-III containing 10 mM of citrate. Measurements included cell count, blood gases, flow cytometry analysis of surface activation markers, and aggregation. RESULTS: Study 1 identified that inclusion of citrate in PAS resulted in a dose-dependent increase in glucose utilization, lactate formation, P-selectin expression, phosphatidylserine (PS) exposure, and reactive oxygen species (ROS) formation. Study 2 showed similar results in which platelets stored in citrate-free PAS-III benefited through better maintenance of glucose utilization with less lactate production, P-selectin expression, PS exposure, and ROS formation compared to citratecontaining PAS-III. Platelets stored in citrate-free PAS-III had aggregation responses that were at least 10% greater than those platelets stored in PAS-III. CONCLUSION: Storage of apheresis platelets incitrate-free PAS-III improved multiple storage parameters including glucose utilization, lactate production, Pselection expression, PS exposure, and ROS formation and resulted in a modest increase in aggregation.ABBREVIATIONS: ACD = anticoagulant citrate dextrose solution; ADP = adenosine diphosphate; CPD = citrate-phosphate-dextrose; PASs = platelet additive solutions; PS = phosphatidylserine; ROS = reactive oxygen species; TRAP6 = thrombin receptor activator peptide 6.* Significantly different than Day 5, 0 mM citrate bicarbonate levels; one-way analysis of variance, p = 0.029. † Significantly different than Day 5, 0 mM citrate bicarbonate levels; one-way analysis of variance, p = 0.003.

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Section: Discussionmentioning

confidence: 65%

Sodium citrate contributes to the platelet storage lesion

2019

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“…Changing the RBC‐to‐crystalloid ratio may alter the influence of the crystalloids 24 . Similarly, longer mixing times may alter the response of RBCs to crystalloid exposure 45–47 . Though our prior work suggests that mixing catecholamines into the crystalloids does not deleteriously effect deformability, aggregometry, or hemolysis of additive‐free RBCs, 9 we did not evaluate the influence of medications in the present study.…”

Section: Discussionmentioning

confidence: 95%

Mixing commonly used crystalloid solutions with red blood cells in five common additives does not negatively impact hemolysis, aggregometry, or deformability

Yarnoff

Dodd‐o

2020

Transfusion

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Background: Literature is beginning to challenge the belief that it is unsafe to coinfuse red blood cells (RBCs) with solutions other than isotonic saline. We recently showed that additive-free RBCs tolerated coincubation with Plasma-Lyte or catecholamines dissolved in normal saline (NS), though 5% dextrose in water (D5W) promoted hemolysis. Herein, we evaluate the effect of coincubating crystalloids on additive-preserved RBC hemolysis, aggregation, and membrane deformability. Study Design and Methods: RBCs were coincubated 5 minutes with plasma, NS, Plasma-Lyte, lactated Ringer's (LR) or D5W (1 mL PRBC +131.3 μL solution). Samples were then assessed for hemolysis (free hemoglobin), aggregation (critical shear stress [mPa]), and membrane deformability (elongation index [EI]). Significance (P ≤ .05) by t test or ANOVA with post-hoc Tukey-Kramer test. Results: Additive-prepared RBCs coincubated with crystalloid instead of plasma demonstrated: (a) no increase in hemolysis as indicated by plasma free hemoglobin levels that is likely to be clinically relevant; (b) no increase, but in some cases a decrease, in aggregation as indicated by critical shear stress; and (c) in some combinations, a deterioration in deformability. When present, the deformability decrease was likely clinically insignificant in degree, and always returned to normal when the crystalloid was subsequently diluted out with plasma. Conclusion: Our data suggest that additive-prepared RBCs coincubated for 5 minutes with any of four common crystalloids demonstrate no clinically relevant increased lysis, increased aggregation, or decreased deformability.

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“…43 Second, we were limited to the Food and Drug Administration-approved saline washing solution, whereas the balanced solution Plasmalyte-A (Baxter, USA), appears to be associated with less hemolysis than saline, which has an unphysiologically high chloride level of 154 mM and an acidic pH of 5.5. 44 Future bedside washing protocols to be evaluated include simplifying the workflow by dilution with 1,000 (approximately 1:3) rather than the current 1,200 ml (1:4), using other cell saver devices, optimizing erythrocyte by diluting and washing with Plasmalyte A or other balanced, neutral solutions or even reversing aspects of the erythrocyte storage lesion by replenishing 2,3-diphosphoglycerate or removing toxic phthalates. 45 While our median postwash cell-free hemoglobin value of 210 mg/dl is similar to a mean postwash value of 212 mg/dl previously reported using a spectrophotometric technique, 43 the extreme values seen with our ELISA platform that required serial dilutions for most of our samples present the possibility of error.…”

Section: Bedside Allogeneic Erythrocyte Washingmentioning

confidence: 99%

Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles

et al. 2021

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Background Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank–based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. Methods There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at –70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. Results Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. Conclusions Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Decreased Hemolysis and Improved Platelet Function in Blood Components Washed With Plasma-Lyte A Compared to 0.9% Sodium Chloride

Abstract: PL-A showed less RBC hemolysis and better platelet function than NS. Whether such differences would occur in vivo is unknown.

Cited by 18 publications

References 36 publications

Sodium citrate contributes to the platelet storage lesion

Sodium citrate contributes to the platelet storage lesion

Mixing commonly used crystalloid solutions with red blood cells in five common additives does not negatively impact hemolysis, aggregometry, or deformability

Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles

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