Acute Pulmonary Injury in Hematology Patients Supported with Pathogen Reduced and Conventional Platelet Components.

Patients treated with anti-neoplastic therapy often develop thrombocytopenia requiring platelet transfusion which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen reduced platelet components (PRPC) do not potentiate pulmonary dysfunction compared to conventional platelet components (CPC). A prospective, multi-center, open label, sequential cohort study evaluated the incidence of treatment emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE), and the incidence of treatment emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC, 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference = -1.5%, 95% CI: (-2.7%, -0.2%). In patients requiring ≥ 2 PC the incidence of TEAMV-PD was reduced for PRPC recipients compared to CPC (treatment difference = -2.4%, 95% CI: (-4.2%, -0.6%). CSPAE increased with increasing PC exposure; but were not significantly different between the cohorts. For patients receiving 2 or more platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6 % CPC recipients, p = 0.086. Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared to CPC with 99.2% and 88.8% probability, respectively. In this study, PRPC compared to CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in platelet transfusion dependent hematology patients. CT # NCT02549222.

Development of New Donor-Specific and Human Leukocyte Antigen Antibodies After Transfusion in Adult Lung Transplantation.

OBJECTIVES: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. DESIGN: A retrospective observational study. SETTING: At a single academic tertiary center. PARTICIPANTS: Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). CONCLUSIONS: Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation.

Massive Transfusion Protocol Adherence: Relationship to Trauma Patient Outcomes.

BACKGROUND: Ongoing evaluation of massive transfusion protocol adherence is critical to ensure better trauma patient outcomes. OBJECTIVE: This quality improvement initiative aimed to determine provider adherence to a recently revised massive transfusion protocol and its relationship to clinical outcomes among trauma patients requiring massive transfusion. METHODS: A retrospective, descriptive, correlational design was used to determine the association between provider adherence to a recently revised massive transfusion protocol and clinical outcomes in trauma patients with hemorrhage treated at a Level I trauma center from November 2018 to October 2020. Patient characteristics, provider massive transfusion protocol adherence, and patient outcomes were assessed. Patient characteristics and massive transfusion protocol adherence associations with 24-hr survival and survival to discharge were determined using bivariate statistical methods. RESULTS: A total of 95 trauma patients with massive transfusion protocol activation were evaluated. Of the 95, 71 (75%) survived the initial 24 hr following massive transfusion protocol activation and 65 (68%) survived to discharge. Based on protocol applicable items, the median massive transfusion protocol overall adherence rate per patient was 75% (IQR = 57.1-85.7) for the 65 survivors and 25% (IQR = 12.5-50.0) for the 21 nonsurvivors to discharge whose death occurred at least 1 hr after massive transfusion protocol activation (p < .001). CONCLUSION: Findings indicate the importance of ongoing evaluations of adherence to massive transfusion protocols in hospital trauma settings to target areas for improvement.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Hospital red blood cell and platelet supply and utilization from March to December of the first year of the COVID-19 pandemic: The BEST collaborative study.

BACKGROUND: At the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19. STUDY DESIGN AND METHODS: Weekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline). RESULTS: RBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p < .001) and 5% fewer RBCs were transfused per week compared to 2019 (477 vs. 501, p < .001). However, during the first COVID-19 peak, RBC and PLT inventories were higher than normal, as reflected by deviation from par, days on hand, and percent outdated. At this time, 16% fewer inpatient beds were occupied, and 43% fewer surgeries were performed compared to 2019 (p < .001). In contrast to 2019 when there was no correlation, there was, in 2020, significant negative correlations between RBC and PLT days on hand and both percentage occupancy of inpatient beds and percentage of surgeries performed. CONCLUSION: During the COVID-19 pandemic in 2020, RBC and PLT inventories remained adequate. During the first wave of cases, significant decreases in patient care activities were associated with excess RBC and PLT supplies and increased product outdating.

Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components.

BACKGROUND: Platelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. STUDY DESIGN: An open label, sequential cohort study of transfusion-dependent hematology-oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment-emergent assisted mechanical ventilation (TEAMV) by non-inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri-transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. RESULTS: By modified intent-to-treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non-inferior to CPC for TEAMV (treatment difference -1.7%, 95% CI: (-3.3% to -0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC. DISCUSSION: PRPC demonstrated reduced TEAMV with no excess treatment-related pulmonary morbidity.

Blood product transfusion and lung transplant outcomes: A systematic review.

The perioperative transfusion of blood products has long been linked to development of acute lung injury and associated with mortality across both medical and surgical patient populations.1,2 The need for blood product transfusion during and after lung transplantation is common and, in many instances, unavoidable. However, this practice may potentially be modifiable.3 In this systematic review, we explore and summarize what is known regarding the impact of blood product transfusion on outcomes following lung transplantation, highlighting the most recent work in this area. Overall, the majority of the literature consists of single center retrospective analyses or the work of multicenter working groups referencing the same database. In the end, there are a number of remaining questions regarding blood product transfusion and their downstream effects on graft function and survival.

Massive Transfusion Protocol Predictive Modeling in the Modern Electronic Medical Record.

Objectives: Integrate a predictive model for massive transfusion protocol (MTP) activation and delivery in the electronic medical record (EMR) using prospectively gathered data; externally validate the model and assess the accuracy and precision of the model over time. Background: The Emory model for predicting MTP using only four input variables was chosen to be integrated into our hospital's EMR to provide a real time clinical decision support tool. The continuous variable output allows for periodic re-calibration of the model to optimize sensitivity and specificity. Methods: Prospectively collected data from level 1 and 2 trauma activations were used to input heart rate, systolic blood pressure, base excess (BE) and mechanism of injury into the EMR-integrated model for predicting MTP activation and delivery. MTP delivery was defined as: 6 units of packed red blood cells/6 hours (MTP1) or 10 units in 24 hours (MTP2). The probability of MTP was reported in the EMR. ROC and PR curves were constructed at 6, 12, and 20 months to assess the adequacy of the model. Results: Data from 1162 patients were included. Areas under ROC for MTP activation, MTP1 and MTP2 delivery at 6, 12, and 20 months were 0.800, 0.821, and 0.831; 0.796, 0.861, and 0.879; and 0.809, 0.875, and 0.905 (all P < 0.001). The areas under the PR curves also improved, reaching values at 20 months of 0.371, 0.339, and 0.355 for MTP activation, MTP1 delivery, and MTP2 delivery. Conclusions: A predictive model for MTP activation and delivery was integrated into our EMR using prospectively collected data to externally validate the model. The model's performance improved over time. The ability to choose the cut-points of the ROC and PR curves due to the continuous variable output of probability of MTP allows one to optimize sensitivity or specificity.

The effect of pathogen inactivation on cryoprecipitate: a functional and quantitative evaluation.

BACKGROUND: As a pooled donor blood product, cryoprecipitate (cryo) carries risks of pathogen transmission. Pathogen inactivation (PI) improves the safety of cryoprecipitate, but its effects on haemostatic properties remain unclear. This study investigated protein expression in samples of pathogen inactivated cryoprecipitate (PI-cryo) using non-targeted quantitative proteomics and in vitro haemostatic capacity of PI-cryo. MATERIALS AND METHODS: Whole blood (WB)- and apheresis (APH)-derived plasma was subject to PI with INTERCEPT® Blood System (Cerus Corporation, Concord, CA, USA) and cryo was prepared from treated plasma. Protein levels in PI-cryo and paired controls were quantified using liquid chromatography-tandem mass spectrometry. Functional haemostatic properties of PI-cryo were assessed using a microparticle (MP) prothrombinase assay, thrombin generation assay, and an in vitro coagulopathy model subjected to thromboelastometry. RESULTS: Over 300 proteins were quantified across paired PI-cryo and controls. PI did not alter the expression of coagulation factors, but levels of platelet-derived proteins and platelet-derived MPs were markedly lower in the WB PI-cryo group. Compared to controls, WB (but not APH) cryo samples demonstrated significantly lower MP prothrombinase activity, prolonged clotting time, and lower clot firmness on thromboelastometry after PI. However, PI did not affect overall thrombin generation variables in either group. DISCUSSION: Data from this study suggest that PI via INTERCEPT® Blood System does not significantly impact the coagulation factor content or function of cryo but reduces the higher MP content in WB-derived cryo. PI-cryo products may confer benefits in reducing pathogen transmission without affecting haemostatic function, but further in vivo assessment is warranted.

Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients.

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. RESULTS: Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. CONCLUSION: The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.

Management of Blood Product Market Withdrawals - A Single Institution's Process and Experience.

OBJECTIVE: While lookback investigations follow specific Food and Drug Administration (FDA) requirements, the management of blood product market withdrawals from suppliers varies widely. Follow-up data are limited, prompting this analysis of the types and reasons for recipient notification and their outcomes. METHODS: A single institution retrospective review of market withdrawal and lookback files from 2012-2015 included product type, reason, FDA category, notification, and turnaround time. Descriptive statistics and chi-square analysis were performed. RESULTS: Over 4 years, 796/229,549 (0.35%) blood components were implicated in supplier notifications, including market withdrawals (84.3%) and lookbacks (15.7%). Seventy-nine cases resulted in patient notification. 97% of patient notifications were achieved within 3 months. Plasma with human leukocyte antigen antibodies was the most common reason for withdrawal (20.5%). Category 1 notifications were the most commonly reported by this transfusion service, apart from in 2015 when category 4 notifications were highest. Over four years, the proportion of notifications by category remained relatively stable. CONCLUSIONS: Market withdrawal investigations involve significant effort to review, document, and appropriately notify. Standardized management and centralized reporting of recipient notification of market withdrawals may improve this process.

The Association of Increased FFP:RBC Transfusion Ratio to Primary Graft Dysfunction in Bleeding Lung Transplantation Patients.

OBJECTIVES: Lung transplantation is associated with a significant risk of needed transfusion. Although algorithm-based transfusion strategies that promote a high fresh frozen plasma:red blood cells (FFP:RBC) ratio have reduced overall blood product requirements in other populations, large-volume transfusions have been linked to primary graft dysfunction (PGD) in lung transplantation, particularly use of platelets and plasma. The authors hypothesized that in lung transplant recipients requiring large-volume transfusions, a higher FFP:RBC ratio would be associated with increased PGD severity at 72 hours. DESIGN: Observational retrospective review. SETTING: Single tertiary academic center. PARTICIPANTS: Adult patients undergoing bilateral or single orthotopic lung transplantation and receiving >4 U PRBC in the first 72 hours from February 2014 to March 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, operative characteristics, blood transfusions, and outcomes including PGD scores and length of stay were collected. Eighty-nine patients received >4U PRBC, had available 72-hour PGD data, and were included in the study. These patients were grouped into a high-ratio (>1:2 units of FFP:RBC, N = 38) or low-ratio group (<1:2 units of FFP:RBC, N = 51). Patients in the high-ratio group received more transfusions and factor concentrates and had significantly longer case length. The high-ratio group had a higher rate of severe PGD at 72 hours (60.5% v 23.5%, p = 0.0013) and longer hospital length of stay (40 v 32 days, p = 0.0273). CONCLUSIONS: In bleeding lung transplantation patients at high risk for PGD, a high FFP:RBC transfusion ratio was associated with worsened 72-hour PGD scores when compared with the low-ratio cohort.

Comparison of the platelet activation status of single-donor platelets obtained with two different cell separator technologies.

BACKGROUND: The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS: Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS: Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P < .0001). Multivariable analysis identified apheresis platform as significantly associated with platelet activation, with a lower activation rate for Trima than Amicus (RR: 0.641, 95% confidence interval [CI]: 0.578; 0.711, P < .0001) and a 6.901% (95% CI: 5.926; 7.876, P < .0001) absolute reduction in MP%, when adjusting for the other variables. CONCLUSION: Trima-collected platelets were significantly less likely to be activated than Amicus-collected platelets, irrespective of the storage medium, the use of pathogen reduction, storage time, and testing site.

Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease.

BACKGROUND: Red blood cell (RBC) exchange (RCE) transfusion therapy is indicated for certain patients with sickle cell disease (SCD). Although beneficial, this therapy is costly and inconvenient to patients, who may require it monthly or more often. Identification of blood and plasma biomarkers that could improve or help individualise RCE therapy is of interest. Here we examined relevant blood and plasma metabolites and biomarkers of vasoactivity and RBC fragility in a pilot study of SCD patients undergoing RCE using either standard RBC units or RBC units treated with a US Food and Drug Administration (FDA)-approved additive solution containing phosphate, inosine, pyruvate, and adenine ("PIPA"). MATERIALS AND METHODS: In this prospective, single-blind, cross-over pilot clinical trial, patients were randomised to receive either standard RBC exchange or PIPA-treated RBC exchange transfusion with each RCE session over a 6-month treatment period. Pre- and post-transfusion blood samples were obtained and analysed for RBC O2 affinity, ATP, purine metabolites, RBC microparticles, and cell free haemoglobin. RESULTS: Red blood cell O2 affinity was maintained after PIPA-RCE in contrast to standard RCE, after which P50 fell (net O2 affinity rose). Plasma ATP did not change significantly after RCE using either of the RBC unit types. Exchange transfusion with PIPA-treated RBC units led to modest increases in plasma inosine and hypoxanthine. Plasma cell free haemoglobin fell after either standard or PIPA-treated RBC exchange transfusion (novel findings), and to a similar extent. RBC-derived microparticles in the plasma fell significantly and similarly after both standard and PIPA-treated RCE transfusion. DISCUSSION: In summary, treatment of RBCs with PIPA prior to RCE elicited favourable or neutral changes in key metabolic and vascular biomarkers. Further study of its efficacy and safety is recommended and could ultimately serve to improve outcomes in chronically transfused SCD patients.

Rejuvenation solution as an adjunct cold storage solution maintains physiological haemoglobin oxygen affinity during early-storage period of red blood cells.

BACKGROUND: Red blood cell (RBC) units accumulate morphologic and metabolic lesions during storage before transfusion. Pyruvate-inosine-phosphate-adenine (PIPA) solutions (Rejuvesol, Biomet, Warsaw, IN) can be incubated with RBC units to mitigate storage lesions. This study proposes a PIPA treatment process, termed cold 'rejuvenation', using Rejuvesol as an adjunct additive solution, to prevent biomechanical storage lesions while avoiding the 1 h PIPA incubation required with standard PIPA treatment. We compared the efficacy of cold to standard 'rejuvenation' in improving metabolic lesions that occur during cold storage of RBCs, without altering function. METHODS: Twelve leucoreduced, A-positive RBC units were obtained. Each unit was aliquoted into either control (standard storage), washed (W), standard rejuvenation (SR) or cold rejuvenation (CR) groups, the latter two requiring washing. A volume-adjusted dose of Rejuvesol was instilled into the CR group upon receipt (Day 3). After 15 days of storage, p50, RBC deformability, in-bag haemolysis and mechanical fragility were analysed. 'Any treatment' is defined as W, SR and CR, with comparisons in reference to control. RESULTS: Higher p50s were seen in rejuvenated groups (>30 mmHg vs. <19 mmHg; P < 0·0001). Any treatment significantly increased elongation index (P = 0·034) but did not significantly increase in-bag haemolysis (P = 0·062). Mechanical fragility was not significantly different between groups (P = 0·055) at baseline, but the control (CTL) group was more fragile after 2 h in a cardiac bypass simulation than any treatment (P < 0·0001). CONCLUSIONS: This study demonstrates that rejuvenation (standard or cold) prevents the leftward p50 shift of storage lesions without detrimental effect on RBC deformity, in-bag haemolysis or mechanical fragility.

Anticoagulation Strategies in the Perioperative Period for Lung Transplant.

Patients who are undergoing lung transplantation may require systemic anticoagulation in the perioperative period for various indications at the time of the procedure. Four-factor prothrombin complex concentrate has been approved in the United States to reverse the effects of warfarin for patients requiring urgent surgery. We describe a perioperative anticoagulation strategy with warfarin that is reversed before incision using 4-factor complex concentrate for off-pump lung transplant recipients.

Presence of a basic secretory protein in xylem sap and shoots of poplar in winter and its physicochemical activities against winter environmental conditions.

XSP25, previously shown to be the most abundant hydrophilic protein in xylem sap of Populus nigra in winter, belongs to a secretory protein family in which the arrangement of basic and acidic amino acids is conserved between dicotyledonous and monocotyledonous species. Its gene expression was observed at the same level in roots and shoots under long-day conditions, but highly induced under short-day conditions and at low temperatures in roots, especially in endodermis and xylem parenchyma in the root hair region of Populus trichocarpa, and its protein level was high in dormant buds, but not in roots or branches. Addition of recombinant PtXSP25 protein mitigated the denaturation of lactate dehydrogenase by drying, but showed only a slight effect on that caused by freeze-thaw cycling. Recombinant PtXSP25 protein also showed ice recrystallization inhibition activity to reduce the size of ice crystals, but had no antifreezing activity. We suggest that PtXSP25 protein produced in shoots and/or in roots under short-day conditions and at non-freezing low temperatures followed by translocation via xylem sap to shoot apoplast may protect the integrity of the plasma membrane and cell wall functions from freezing and drying damage in winter environmental conditions.

Interval decline in hemoglobin A is associated with annual clinical event rate in sickle cell anemia patients receiving maintenance apheresis RBC exchange.

BACKGROUND: Apheresis red blood cell (RBC) exchange (RCE) is a standard intervention for patients with sickle cell anemia (SCA) who have had previous thromboembolic stroke or intractable chronic pain. Replacing sickling cells with those containing hemoglobin A (HbA) minimizes microvascular pathophysiology that produces clinical crises. Limited data exist regarding the interval changes in HbA between transfusions. We sought to describe the HbA decrement between RCE procedures and its relationship to clinical status. STUDY DESIGN AND METHODS: SCA patients (all hemoglobin SS disease) treated with maintenance RCE (n = 21) over a 15-month period at two neighboring institutions were retrospectively reviewed. Time-normalized daily HbA decrement was calculated to reflect loss of transfused RBCs, and annual events of either emergency department or hospital admissions for SCA complications were noted. Associations between HbA decrement and laboratory measures were calculated using mixed linear regression models and unpaired t test was used to compare HbA decrement between high and low event rate groups. RESULTS: A total of 31 events were recorded, and mean HbA decrement per day was 0.77 ± 0.16%. The mean interval between RCEs was 36 ± 12 days. Patients with more annual events exhibited a significantly greater daily HbA decrement (p = 0.007). No significant association between RBC unit age and HbA decrement or annual event rate was observed. CONCLUSIONS: Patients exhibiting greater daily HbA decrement were more likely to have multiple emergency department visits or admissions for sickling crises. Modulating HbA decrement may merit study as an intermediate metric for interventions to improve outcomes in hemoglobin SS disease.