Demand forecasting for platelet usage: From univariate time series to multivariable models.

Platelet products are both expensive and have very short shelf lives. As usage rates for platelets are highly variable, the effective management of platelet demand and supply is very important yet challenging. The primary goal of this paper is to present an efficient forecasting model for platelet demand at Canadian Blood Services (CBS). To accomplish this goal, five different demand forecasting methods, ARIMA (Auto Regressive Integrated Moving Average), Prophet, lasso regression (least absolute shrinkage and selection operator), random forest, and LSTM (Long Short-Term Memory) networks are utilized and evaluated via a rolling window method. We use a large clinical dataset for a centralized blood distribution centre for four hospitals in Hamilton, Ontario, spanning from 2010 to 2018 and consisting of daily platelet transfusions along with information such as the product specifications, the recipients' characteristics, and the recipients' laboratory test results. This study is the first to utilize different methods from statistical time series models to data-driven regression and machine learning techniques for platelet transfusion using clinical predictors and with different amounts of data. We find that the multivariable approaches have the highest accuracy in general, however, if sufficient data are available, a simpler time series approach appears to be sufficient. We also comment on the approach to choose predictors for the multivariable models.

Evaluation of platelets componentized with the Reveos Automated Blood Processing System and stored for 7 days at room temperature in a non-Di(2-ethylhexyl) phthalate (DEHP) platelet pooling set.

BACKGROUND: Platelet concentrates (PCs) used for transfusion can be produced by apheresis or derived from whole blood (WB). The Reveos device is the first US Food and Drug Administration-approved automated blood processing system that can produce PCs. In this work, we evaluated the quality and function of Reveos-collected PCs stored for 7 days at room temperature. STUDY DESIGN AND METHODS: WB was collected from healthy donors and componentized on the day of collection (Fresh) or after an overnight hold (Overnight). PCs were produced (n = 7 Fresh; n = 6 Overnight), stored at room temperature in plasma, and evaluated on days 1 and 7 for quality metrics, platelet activation, clot formation, and aggregation response. RESULTS: Platelet count was comparable between Fresh and Overnight PCs. A drop in pH was reported in Fresh day 7 PCs (p < .001, vs. day 1) but not in Overnight. Overnight units displayed the lowest levels of P-selectin expression (p = .0008, vs. day 7 Fresh). Reduced clot strength and increased lysis were observed in both Fresh and Overnight units on day 7 (vs. day 1). Overnight-hold PCs resulted in the highest clot strength on day 7 (p = .0084, vs. Fresh). No differences in aggregation were reported between groups. CONCLUSION: Reveos-processed PCs produced from overnight-hold WB performed better in hemostatic function assays and displayed reduced activation compared to fresh WB-derived PCs, although both PC groups maintained platelet quality throughout storage. Utilization of overnight WB for PC preparation with Reveos holds promise as an alternative method of producing platelets for transfusion purposes.

Platelet dysfunction reversal with cold-stored vs room temperature-stored platelet transfusions.

ABSTRACT: Platelets are stored at room temperature for 5 to 7 days (room temperature-stored platelets [RSPs]). Because of frequent and severe shortages, the US Food and Drug Administration recently approved up to 14-day cold-stored platelets (CSPs) in plasma. However, the posttransfusion function of CSPs is unknown and it is unclear which donors are best suited to provide either RSPs or CSPs. In this study, we sought to evaluate the posttransfusion platelet function and its predictors for platelets stored for the maximum approved storage times (7-day RSPs and 14-day CSPs) in healthy volunteers on acetylsalicylic acid (ASA). We conducted a randomized crossover study in 10 healthy humans. Individuals donated 1 platelet unit, stored at either 22°C or 4°C based on randomization. Before transfusion, participants ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round of transfusion with the alternative product was followed by an identical testing sequence. RSPs reversed platelet inhibition significantly better in αIIbß3 integrin activation-dependent assays. In contrast, CSPs in recipients led to significantly more thrombin generation, which was independent of platelet microparticles. Lysophosphatidylcholine-O species levels predicted the procoagulant capacity of CSPs. In contrast, polyunsaturated fatty acid concentrations predicted the aggregation response of RSPs. In summary, we provide, to our knowledge, the first efficacy data of extended-stored CSPs in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible, and pave the way for larger studies in the future. This trial is registered at www.ClinicalTrials.gov as #NCT0511102.

Trend towards reduction of transfusion reactions using prestorage leukocyte-reduced and pooled whole blood-derived platelets and cost savings compared with poststorage whole blood-derived random platelets as evidenced by real-time hemovigilance.

BACKGROUND: Due to chemotherapy-induced neutropenia or hematologic malignancies, immunocompromised cancer patients may have higher incidence of febrile nonhemolytic transfusion reactions compared with the general population and frequently require platelet transfusions. This quality improvement project compared the safety of transfusion using prestorage leukocyte-reduced and pooled whole blood-derived platelets (Acrodose/WBD) with conventionally produced poststorage WBD platelets (RDP) using an active hemovigilance system. METHODS: Every patient receiving a blood product at the hospital was virtually monitored in real time by trained nurses from a remote hemovigilance unit. These nurses monitor a digital dashboard, which populates a watch list of patients from the time blood product administration is initiated until 12 hours posttransfusion. Over the course of 6 months, 371 patients receiving 792 RDP transfusions and 423 patients receiving 780 Acrodose/WBD platelets transfusions were monitored for transfusion reactions. RESULTS: We identified 26 transfusion reactions in RDP but only 12 transfusion reactions in the Acrodose/WBD platelet group. CONCLUSION: Acrodose platelet transfusion was associated with fewer transfusion reactions, which resulted in significant cost savings.

Optimal dose of cryoprecipitate in massive transfusion following trauma.

BACKGROUND: While cryoprecipitate (Cryo) is commonly included in massive transfusion protocols for hemorrhagic shock, the optimal dose of Cryo transfusion remains unknown. We evaluated the optimal red blood cell (RBC) to RBC to Cryo ratio during resuscitation in massively transfused trauma patients. METHODS: Adult patients in the American College of Surgeon Trauma Quality Improvement Program (2013-2019) receiving massive transfusion (≥4 U of RBCs, ≥1 U of fresh frozen plasma, and ≥1 U of platelets within 4 hours) were included. A unit of Cryo was defined as a pooled unit of 100 mL. The RBC:Cryo ratio was calculated for blood products transfused within 4 hours of presentation. The association between RBC:Cryo and 24-hour mortality was analyzed with multivariable logistic regression adjusting for the volume of RBC, plasma and platelet transfusions, global and regional injury severity, and other relevant variables. RESULTS: The study cohort included 12,916 patients. Among those who received Cryo (n = 5,511 [42.7%]), the median RBC and Cryo transfusion volume within 4 hours was 11 U (interquartile range, 7-19 U) and 2 U (interquartile range, 1-3 U), respectively. Compared with no Cryo administration, only RBC:Cryo ratios ≤8:1 were associated with a significant survival benefit, while lower doses of Cryo (RBC:Cryo >8:1) were not associated with decreased 24-hour mortality. Compared with the maximum dose of Cryo administration (RBC:Cryo, 1:1-2:1), there was no difference in 24-hour mortality up to RBC:Cryo of 7:1 to 8:1, whereas lower doses of Cryo (RBC:Cryo, >8:1) were associated with significantly increased 24-hour mortality. CONCLUSION: One pooled unit of Cryo (100 mL) per 7 to 8 U of RBCs could be the optimal dose of Cryo in trauma resuscitation that provides a significant survival benefit while avoiding unnecessary blood product transfusions. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

The platelet storage lesion, what are we working for?

BACKGROUND: Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions. OBJECTIVE: This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures. CONCLUSION: Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.

Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Cold platelet transfusion: The effects of a fluid warmer on platelet function.

BACKGROUND: Recently the US Food and Drug Administration has granted variances to select blood centers to supply cold-stored platelet components (CSP). In hemorrhage resuscitation warming of blood components with approved fluid warming devices is common. STUDY DESIGN AND METHODS: Pathogen-reduced apheresis platelet units were collected and stored in one of two ways: (1) CSP-I, (2) CSP-D. CSP-I were collected and immediately stored at 1-6°C until used. CSP-D were collected and stored at 20-24°C for 5 days and transferred to storage at 1-6°C until use. Aggregometry using arachidonic acid (AA), adenosine diphosphate (ADP) and collagen as agonists was performed on the unit samples before and after the units were infused through a Ranger blood-warming device. RESULTS: CSP-I, 23 units, had very high aggregation responses to all agonists (all ≥47.6 ± 20.7). There was a statistically significant reduction in ADP-induced aggregometry results from 55.1 ± 23.2 before compared to 33.5 ± 14.6 following infusion of the PLT through the blood warmer (p < .001). There were no differences in AA and collagen aggregometry results before and after the infusion of the platelets through the blood warmer. CSP-D had 5 of the 15 units with visible clotting in the bag. The 10 CSP-Ds studied had lower aggregation than all agonists before and after infusion through the blood-warming device (all ≤49.9 ± 35.9). CONCLUSION: We detected a statistically significant reduction in ADP-induced aggregometry in CSP-I run through a Ranger blood-warming device with no change with AA or collagen agonist aggregometry.

Prophylactic Platelet Transfusion: Is There Evidence of Benefit, Harm, or No Effect?

The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion. In addition, while prophylactic platelet transfusions are administered with the goal of enhancing hemostasis, increasing evidence supports critical nonhemostatic roles for platelets related to innate and adaptive immunity, inflammation, and angiogenesis, which may impact patient responses and outcomes. Here we review several recent studies conducted in adult or pediatric patients that highlight the limitations in our current understanding of prophylactic platelet transfusion. Together, these studies underscore the need for additional research, especially in the form of robust randomized clinical trials and integrating additional parameters beyond the platelet count. Future research at the basic, translational, and clinical levels will best define the optimal role for prophylactic transfusion across the lifespan and its broader impact on health and disease.

Omics markers of platelet transfusion in trauma patients.

BACKGROUND: Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. MATERIALS AND METHODS: To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. RESULTS: Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). DISCUSSION: The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

TSR: A User-Friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-Incompatible Hematopoietic Stem Cell Transplantation.

OBJECTIVE: Patients undergoing hematopoietic stem cell transplant (HSCT) need frequent transfusions, until their red blood cells (RBCs) and platelets start to recover. The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process. To date, there is no user-friendly tool to choose the right blood product for transfusion treatment, despite the number of guidelines and expert advice on the subject. METHODS: R/shiny is a powerful programming language for clinical data analysis and visualization. It can create interactive web applications that work in real-time. The web application named TSR was built using R programming, simplifying blood transfusion practice for ABO-incompatible HSCT with a one-click solution. RESULTS: The TSR is divided into four main tabs. The home tab provides an overview of the application, while RBC, plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category. Unlike traditional methods that rely on treatment guidelines and specialist consensus, TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters, providing an innovative approach to improve transfusion support. CONCLUSION: The present study highlights that the TSR enables real-time analysis, and promotes transfusion practice by offering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT. TSR has the potential to become a widely-utilized tool for transfusion services, providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Whole blood derived and apheresis platelets: Opinions and preferences-the results of a national survey of blood collectors.

INTRODUCTION: Currently greater than 94% of the US platelet supply is collected by apheresis. A survey to determine the attitudes of members of America's Blood Centers (ABC) toward whole blood derived (WBD) platelets was designed in light of current platelet supply issues. METHODS: An on-line survey was distributed to medical directors of the 47 ABC members. RESULTS: Responses were received from 44/47 (94%) ABC members. There were 15/43 (35%) centers that are currently providing WBD platelets. Seventy percent of the respondents agreed or agreed strongly that WBD and apheresis platelets were clinically equivalent, with approximately 16% indicating that they did not have an opinion on their equivalency and 14% indicating that they were not clinically equivalent. Forty-four percent of respondents felt that their customers would agree or strongly agree that these products are clinically equivalent, while 26% felt that their customers did not know or were neutral on clinical equivalency. The main barrier to WBD platelet implementation was logistic/inventory management issues, followed by bacterial contamination risk mitigation. There were 21/43 (49%) respondents who indicated they are not considering producing WBD platelets to mitigate shortages. Respondents indicated they might begin producing WBD platelets if there was evidence of increasing customer demand, increased reimbursement, inability to supply apheresis platelets, if pathogen reduction became available for WBD platelets, if the platelet shortage worsened. CONCLUSIONS: The majority of blood collectors consider WBD platelets clinically equivalent to apheresis, however wider adoption of WBD platelets is still hindered by challenges with logistics and inventory management.

Epidemiology of Platelet Transfusions in Hospitalized Children: A Pediatric Hospital Information System Database Study.

OBJECTIVES: To describe the epidemiology and complications of platelet transfusions among hospitalized pediatric patients during 2010 to 2019. METHODS: We performed a retrospective cohort study of hospitalized children within the Pediatric Health Information System database. Pediatric encounters receiving at least one platelet transfusion during hospitalization from 2010 to 2019 were identified. Data regarding demographics, diagnoses, procedures required during hospitalization, complications, and outcomes were extracted for eligible encounters. RESULTS: Within the Pediatric Health Information System database, 6 284 264 hospitalizations occurred from 2010 to 2019. A total of 244 464 hospitalizations required at least one platelet transfusion, yielding a prevalence of 3.89% (95% confidence interval [CI], 3.87%-3.91%). Transfusion prevalence did not change significantly across the decade (P value = .152). Two-thirds of children receiving platelet transfusions were in their first 6 years of life, and the majority identified as male (55%). Recipients most commonly had diseases of the circulatory system (21%, 52 008 of 244 979), perinatal disorders (16%, 38 054 of 244 979), or diseases of the hematologic/immune systems (15%, 37 466 of 244 979). When adjusted for age, support by extracorporeal membrane oxygenation, mechanical ventilation, surgical intervention, and diagnostic category, the odds of thrombosis, infection, and mortality increased by 2% (odds ratio [OR], 1.02; 95% CI, 1.016-1.020), 3% (OR, 1.03; 95% CI, 1.028-1.033), and 7% (OR, 1.07; 95% CI, 1.067-1.071), respectively, with each additional transfusion. CONCLUSIONS: The prevalence of platelet transfusions among pediatric inpatients remained consistent across the decade. Our finding that increasing numbers of transfusions may be associated with elevated morbidity and mortality is consistent with other observation and experimental studies, highlighting the need to be thoughtful in weighing risks and benefits when prescribing repeated platelet transfusions to hospitalized children.

Digital polymerase chain reaction to monitor platelet transfusions in cardiac surgery patients.

BACKGROUND AND OBJECTIVES: Corrected count increment (CCI) measurements monitor the effectiveness of platelet transfusions in haemato-oncology, but they usually fail in patients undergoing cardiac surgery. We investigated whether polymerase chain reaction (PCR) of mitochondrial single-nucleotide polymorphisms (SNPs) is able to monitor the survival of transfused platelets in these patients. MATERIALS AND METHODS: Leukocyte-free, platelet-rich plasma was prepared from patients' blood to measure platelet counts based on patient-/donor-specific SNPs by digital PCR after DNA extraction. Platelet counts in samples from patients with severe thrombocytopenia were analysed by both PCR and flow cytometry. Ten patients undergoing cardiac surgery with the use of heart lung machine and without overt bleeding received a single apheresis platelet concentrate because of either dual platelet inhibition during a non-elective intervention or a complex procedure. Blood samples were collected at nine defined intervals (0-120 h) post transfusion. RESULTS: The digital PCR of the seven SNPs reliably quantified levels ≥0.6 G/L platelets, in good agreement with flow cytometry and without interference by other SNPs or by platelet activation. A mean 24-h CCI of 11.8 (range: 5.6-19.8) and a mean 120-h area under the curve (AUC) of 1386 (915-1821) hxG/L were observed for the transfused platelets. The mean AUC of 14,103 (3415-27,305) hxG/L for the patients' endogenous platelets indicates that transfused platelets represented only 11% (5-25) of the total platelet counts during 120 h post transfusion. CONCLUSION: PCR of mitochondrial SNPs offers a tool to assess the survival of platelets from apheresis concentrates in cardiac surgery patients to facilitate the implementation of improved transfusion strategies.

Transfusion of Adult, but Not Neonatal, Platelets Promotes Monocyte Trafficking in Neonatal Mice.

BACKGROUND: Thrombocytopenia is common in preterm neonates. Platelet transfusions are sometimes given to thrombocytopenic neonates with the hope of reducing the bleeding risk, however, there are little clinical data to support this practice, and platelet transfusions may increase the bleeding risk or lead to adverse complications. Our group previously reported that fetal platelets expressed lower levels of immune-related mRNA compared with adult platelets. In this study, we focused on the effects of adult versus neonatal platelets on monocyte immune functions that may have an impact on neonatal immune function and transfusion complications. METHODS: Using RNA sequencing of postnatal day 7 and adult platelets, we determined age-dependent platelet gene expression. Platelets and naive bone marrow-isolated monocytes were cocultured and monocyte phenotypes determined by RNA sequencing and flow cytometry. An in vivo model of platelet transfusion in neonatal thrombocytopenic mice was used in which platelet-deficient TPOR (thrombopoietin receptor) mutant mice were transfused with adult or postnatal day 7 platelets and monocyte phenotypes and trafficking were determined. RESULTS: Adult and neonatal platelets had differential immune molecule expression, including Selp. Monocytes incubated with adult or neonatal mouse platelets had similar inflammatory (Ly6Chi) but different trafficking phenotypes, as defined by CCR2 and CCR5 mRNA and surface expression. Blocking P-sel (P-selectin) interactions with its PSGL-1 (P-sel glycoprotein ligand-1) receptor on monocytes limited the adult platelet-induced monocyte trafficking phenotype, as well as adult platelet-induced monocyte migration in vitro. Similar results were seen in vivo, when thrombocytopenic neonatal mice were transfused with adult or postnatal day 7 platelets; adult platelets increased monocyte CCR2 and CCR5, as well as monocyte chemokine migration, whereas postnatal day 7 platelets did not. CONCLUSIONS: These data provide comparative insights into adult and neonatal platelet transfusion-regulated monocyte functions. The transfusion of adult platelets to neonatal mice was associated with an acute inflammatory and trafficking monocyte phenotype that was platelet P-sel dependent and may have an impact on complications associated with neonatal platelet transfusions.

Therapeutic efficacy of platelet transfusion treated with amotosalen/UVA pathogen inactivation technology (INTERCEPTTM Blood System) in acute myeloid leukemia patients undergoing chemotherapy with curative intent: a single center experience.

BACKGROUND: The INTERCEPTTM Blood System (Intercept Blood System, Cerus Europe BV, Amersfoort, the Netherlands) has been used to reduce or inactivate pathogen load in platelet concentrates in France for three years. MATERIALS AND METHODS: After comparing the transfusion efficiency between pathogen-reduced platelets (PR_PLT) and untreated platelet products (U_PLT), our single-center observational study assessed the effectiveness of PR_PLT for the prevention of bleeding and for therapeutic treatment of WHO grade 2 bleeding in 176 patients undergoing chemotherapy with curative intent for acute myeloid leukemia (AML). The main endpoints were the 24-hour (h) corrected count increment (24h_CCI) after each transfusion, and time to next transfusion. RESULTS: Whereas the transfused doses tended to be higher in the PR_PLT group compared to U_PLT, there was a significant difference in intertransfusion interval (ITI) and 24h_CCI. In prophylactic transfusions, PR_PLT transfusions of >0.65×1011/10 kg, regardless of the age of the product (day 2 to day 5), resulted in a 24h_CCI similar to that of the untreated platelet product; this meant the patient could be transfused at least every 48h. In contrast, most PR_PLT transfusions of <0.55×1011/10 kg did not achieve a transfusion interval of 48h. In the context of WHO grade 2 bleeding, PR_PLT transfusions >0.65×1011/10 kg and storage of less than 4 days seems more effective in stopping bleeding. DISCUSSION: These results, which must be confirmed by prospective studies, indicate the need for vigilance regarding the quantity and quality of PR_PLT products used to treat patients at risk of bleeding crisis. Future prospective studies are needed to confirm these findings.

Retrospective evaluation of fresh platelet concentrate administration in dogs: Patient characteristics, outcomes, and transfusion practices in 189 transfusion episodes (2008-2019).

OBJECTIVE: To describe patient characteristics, underlying disease processes, clinical outcomes, transfusion dose and type (therapeutic or prophylactic), platelet count changes, and adverse events associated with platelet concentrate (PC) administration in dogs. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: A total of 149 dogs, representing 189 PC transfusion episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In this population, 39 of 149 dogs (26.2%) were diagnosed with primary immune-mediated thrombocytopenia, 22 of 149 (14.8%) had decreased bone marrow production, 12 of 149 (8.0%) received PC during a massive transfusion, 3 of 149 (2.0%) had congenital thrombocytopathia, 59 of 149 (39.6%) had severe thrombocytopenia of other causes, and 14 of 149 (9.4%) underwent transfusion for miscellaneous causes without a documented severe thrombocytopenia. In 117 of 149 dogs (78.5%), >1 site of hemorrhage was noted. The most common sites of hemorrhage were the gastrointestinal (GI) tract in 89 of 149 (59.7%) and the skin in 78 of 149 (52.3%). Overall survival to discharge was 59.1% (88/149). The median PC dose was 0.8 units per 10 kg of body weight per transfusion episode (range: 0.2-6.7). Of 189 episodes, 29 of 189 (15.7%) were prophylactic, and 158 of 189 (83.6%) were therapeutic. For 99 of 189 transfusion episodes, paired pre- and postplatelet counts were available within 24 hours. The median platelet count change was 5.0 × 109 /L (5000/µL; range: -115 × 109 /L to 158 × 109 /L [-115,000 to 158,000/µL]); the posttransfusion platelet count was significantly higher than pretransfusion (P < 0.0001). The increase in platelet count after transfusion was greater in the prophylactic group than the therapeutic group (P = 0.0167). Transfusion reactions were suspected during 2 of 168 episodes (1.2%). CONCLUSIONS: Immune-mediated thrombocytopenia was the most common disease process that resulted in PC transfusion. PC was more frequently administered to animals with active hemorrhage rather than prophylactically, and most dogs had evidence of hemorrhage in multiple organ systems, particularly the GI tract and skin. PC transfusions typically appeared safe, and the median platelet count increased after transfusion.

Three patients highlighting potential pitfalls in platelet refractory testing.

BACKGROUND: Platelet-transfusion refractory (PR) patients do not achieve expected post-transfusion platelet counts. We investigate suspected PR patients with post-transfusion platelet counts, indirect platelet antibody screens (ind-PAS), Class I HLA antibody tests (HLA-Scr), and physical platelet crossmatch (PXM) studies. STUDY DESIGN AND METHODS: The three following cases describe possible pitfalls of laboratory tests used in PR workup and management. RESULTS: Case #1: Antibody testing detected antibodies to only HLA-B13, corresponding to a 4% calculated panel reactive antibodies (CPRA; 96% predicted donor compatibility). However, PXM showed the patient compatible with 11/14 (79%) donors; two of the PXM-incompatible units were ABO-incompatible. Case #2: PXM revealed compatibility with 1/14 screened donors; however, the patient did not respond to the product from the compatible donor. The patient did respond to HLA-matched product. Dilution studies provided evidence of the prozone effect, which caused negative PXM despite clinically relevant antibodies. Case #3: There was a discrepancy between the ind-PAS and HLA-Scr. Ind-PAS was negative for HLA antibodies, while HLA-Scr was positive and specificity testing corresponded to 38% CPRA. Per the package insert, the sensitivity of ind-PAS is ~85% compared to HLA-Scr. DISCUSSION: These cases highlight the importance of investigating incongruent results. Cases #1 and #2 demonstrate PXM pitfalls: ABO incompatibility can result in positive PXM and false-negative PXM can occur in the setting of the prozone effect. Case #3 reveals the importance of knowing a test's sensitivity. Centers that only perform ind-PAS may fail to detect HLA antibodies.