Neonatal Platelet Transfusion Research Articles

EBNEO commentary: Platelet transfusions in neonates and brain development: The new frontier.

Preterm neonates have a high incidence of thrombocytopenia and intraventricular haemorrhage (IVH). Because of this, they are traditionally transfused at higher platelet count (PC) thresholds compared to older children and adults, under the premise that higher PCs decrease bleeding risk.1 Paradoxically, the largest randomised platelet transfusion threshold trial in preterm neonates (PlaNeT-2), found a higher incidence of death or major bleeding within 28 days of randomisation (primary outcome) and a higher incidence of bronchopulmonary dysplasia (BPD) among neonates randomised to a higher platelet transfusion threshold (<50 × 109/L), compared to those randomised to a lower threshold (<25 × 109/L).2 Neonates with a high baseline risk of bleeding and/or death benefited from the lower platelet transfusion threshold as much as low-risk neonates.3 In this manuscript, Moore and collaborators provide evidence that high platelet transfusion thresholds are associated with increased mortality and neurodevelopmental impairment (NDI) at 2 years of corrected age.4 The study had a high follow-up rate (92%), combining results from formal neurodevelopmental (ND) assessment tools (41% of participants), review of medical records, practitioners' notes and early intervention services. Participants were dichotomised as having a favourable or unfavourable outcome (death or severe CP, developmental delay or visual or hearing loss). The combination of different methods to assess ND outcomes is a limitation of the study and restricted the ability of investigators to evaluate subtle deficits or specific neurologic domains. Future trials should include standardised ND assessments at 2 years and be powered for this outcome. Nevertheless, the fact that only severe deficits were included made the findings even more concerning. Given the initial finding that neonates randomised to a higher platelet transfusion threshold had a higher incidence of BPD, the authors performed a post hoc analysis that found a higher need for respiratory support at 2 years among children randomised to the high threshold group. While BPD is common among preterm infants, oxygen dependence or need for respiratory support at 2 years of age is not. Thus, the higher incidence of this outcome among children randomised to the higher threshold suggests platelet transfusions given to high-risk preterm neonates might trigger or enhance pathways leading to severe lung disease. The mechanisms underlying increased morbidity and mortality associated with platelet transfusions are likely related to non-hemostatic effects of platelets. Platelets are critical regulators of immune and inflammatory responses, and it has been hypothesised that adult (transfused) platelets are more pro-inflammatory than neonatal platelets.5-8 In support of this hypothesis, pre-clinical studies suggest platelet transfusions trigger inflammation or dysregulated immune responses in neonates, in a context-dependent manner.9 Whether NDI results from the direct effects of transfused platelets on the developing brain or is mediated by higher rates of IVH and BPD observed in infants randomised to the high threshold group (both of which are associated with NDI), is unknown. Additional studies are needed to define the mechanisms underlying the deleterious and beneficial effects of platelet transfusions, which remain lifesaving in neonates with bleeding or severe thrombocytopenia. In the meantime, this study further supports the use of a restrictive, evidence-based approach to neonatal platelet transfusions. URL LINK: https://ebneo.org/ebneo-commentary-platelet-transfusions-in-neonates-and-brain-development-the-new-frontier/. The authors are supported by grants PO1 HL046925 (MSV), K99 HL156051 (PD) and P01HL152961 (CD). None.

Abstract 380: Adult But Not Neonatal Platelets Promotes Monocyte Trafficking In Neonatal Mice

Background: Platelet transfusions are sometimes given to thrombocytopenic neonates with the hope of reducing the bleeding risk, however, there is 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 to 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: Platelets and bone marrow isolated monocytes were co-cultured and monocyte phenotypes determined by RNA-seq and flow cytometry. An in vivo model of platelet transfusion in neonatal thrombocytopenic mice was used in which platelet deficient thrombopoietin receptor mutant mice (TPOR -/- ) were transfused with adult or P7 platelets and monocyte phenotypes and trafficking were determined. Results: Adult and neonatal platelets had differential immune molecule expression, including Selp (P-selectin). Monocytes incubated with adult or neonatal mouse platelets had similar inflammatory (Ly6C hi ), but different trafficking phenotypes, as defined by CCR2 and CCR5 surface expression. Blocking P-selectin-PSGL-1 interaction, 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 P7 platelets; adult platelets increased monocyte CCR2 and CCR5 as well as monocyte chemokine migration, while P7 platelets did not. Conclusion: These data provide comparative insights into adult and neonatal platelet transfusion regulated monocyte functions.

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

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. 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. 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. 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.

Research Progress in Platelet Transfusion in Neonates

Research Progress in Platelet Transfusion in Neonates

Immunologic effects of red blood cell and platelet transfusions in neonates.

Premature neonates are frequently transfused red blood cells (RBCs) or platelets to raise hemoglobin or platelet counts. However, these transfusions may have unintended effects on the immune system. This review will summarize the newest discoveries on the immunologic effects of RBC and platelet transfusions in neonates, and their potential impact on neonatal outcomes. Neonatal RBC transfusions are associated with increases in plasma pro-inflammatory cytokines, but recent findings suggest sex-specific differential responses. At least one cytokine (monocyte chemoattractant protein-1) rises in females receiving RBC transfusions, but not in males. These inflammatory responses correlate with poorer neurodevelopmental outcomes in heavily transfused female infants, while preterm male infants seem to be more sensitive to severe anemia. Platelet transfusions in preterm neonates are associated with increased neonatal mortality and morbidity. The underlying mechanisms are unknown, but likely related to the immune/inflammatory effects of transfused platelets. Adult platelets are different from neonatal platelets, with the potential to be more pro-inflammatory. Early preclinical data suggest that platelet transfusions alter the neonatal systemic inflammatory response and enhance immune cell migration. RBC and platelet transfusions alter neonatal immune and inflammatory responses. Their pro-inflammatory effects might worsen neonatal disease or affect neurodevelopmental outcomes.

Neonatal platelet transfusions: New evidence and the challenges of translating evidence‐based recommendations into clinical practice

Platelet transfusions are a common intervention for thrombocytopenia. Although the main reason for transfusing platelets is to improve hemostasis, platelets have many additional physiological roles, including interactions with immune pathways. Much of the evidence base for safe and effective transfusions has been informed by randomized trials in adult patients with hematological malignancies. Only three randomized trials have been conducted in sick neonates. These trials have indicated evidence of harm, including a significantly higher rate of death or major bleeding within 28 days after randomization for the largest trial, which enrolled 660 infants. The overall research indicates limited effectiveness of platelet transfusions to reduce bleeding risk. It is important that the results of trials are implemented into practice, but uptake of research findings into neonatal medicine remains inconsistent, as for many areas of health care. There is a need to establish which potential implementation strategies (cost‐) efficiently enact change, such as audit and feedback, automated reminder systems for ordering transfusions, and use of opinion leaders. Research is exploring potential mechanisms underlying the lack of effectiveness of platelet transfusions and the increased bleeding and mortality observed in neonatal randomized trials. One potential mechanism concerns the roles of platelets to promote excessive angiogenic signals during a vulnerable period of brain development. A further hypothesis explores the effects of transfusing “adult” platelets into “neonatal” thrombocytopenic blood on primary hemostasis and immune responses.

Platelet transfusions in neonates-Unresolved aspects and future directions.

Platelet transfusions in neonates-Unresolved aspects and future directions.

Adult, but Not Neonatal, Platelet Transfusions Drive a Monocyte Trafficking Phenotype in Vitro and In Vivo

Although, thrombocytopenia can affect all age groups, neonates, especially pre-term, have an increased incidence of thrombocytopenia. Platelet transfusions may reduce the bleeding risk in neonates, but are also associated with adverse short and long-term immune and inflammatory outcomes. A randomized trial of platelet transfusions in neonates found that transfusion was associated with an increased risk of necrotizing enterocolitis, unilateral/bilateral retinopathy, and bronchopulmonary dysplasia. Past work from our research team found that neonatal platelets expressed lower levels of mRNA for many immune related molecules compared to adult platelets. We therefore sought to determine whether the transfusion of adult platelets to neonates resulted in developmental immune dysregulation, with a focus on platelet and monocyte interactions.To explore the interactions between monocytes and platelets, we isolated monocytes from adult mouse bone marrow and co-incubated monocytes with adult (>8 weeks old) or neonatal mouse platelets (7 days old mice) and determined inflammatory and trafficking monocyte phenotypes by flow cytometry and qRT-PCR. Monocytes treated with adult platelets had an increased inflammatory (Ly6C hi) and trafficking phenotype (CCR2 hi), while monocytes treated with neonatal platelets adopted an inflammatory, but not trafficking phenotype. As expected, adult platelets increased the expression of monocyte inflammatory (Nos2, Cxcl1, Ccl2) and trafficking (Ccr2) mRNA, while neonatal platelets also increased inflammatory mRNA expression, but did not increase Ccr2 expression. Adult platelets express more Selp (P-selectin) than neonatal platelets and P-selectin is a major mediator of platelet and monocyte interactions. We confirmed that adult platelets expressed more P-selectin protein compared to neonatal platelets, and found that blocking P-selectin decreased adult platelet induced CCR2 expression to levels similar to monocytes treated with neonatal platelets. Using a transwell chamber we assessed adult and neonatal platelet effects on monocyte migration towards the CCR2 ligand CCL2. Monocytes were treated with adult platelets had significantly greater monocyte migration compared to monocytes co-incubated with neonatal platelets.To model platelet transfusions in the setting of thrombocytopenia, we used 14d old thrombopoietin receptor knockout mice (TPOR -/-) that have low platelet counts, and infused adult or neonatal platelets. We observed a significant increase in inflammatory and trafficking monocytes in mice transfused with adult platelets compared to those transfused with neonatal platelets. Using an in vivo model of monocyte chemotaxis, mice were treated with CCL2 intraperitoneal after platelet transfusion. Adult platelet transfusions, but not neonatal, increased monocyte peritoneal trafficking to CCL2.These data provide comparative insights as to how adult and neonatal platelet transfusions regulate monocyte functions. Adult platelet transfusions to neonates are associated with an inflammatory and trafficking monocyte phenotype that is platelet P-selectin dependent and may have a major impact on neonatal platelet transfusion complications. DisclosuresPalis: Rubius Therapeutics: Consultancy.

Neonatal Platelet Transfusions: Starting Again.

Preterm neonates with severe thrombocytopenia are frequently prescribed prophylactic platelet transfusions despite no evidence of benefit. Neonatal platelet transfusion practice varies, both nationally and internationally. Volumes and rates of transfusion in neonatology are based on historic precedent and lack an evidence base. The etiology of harm from platelet transfusions is poorly understood. Neonates are expected to be the longest surviving recipients of blood produce transfusions, and so avoiding transfusion associated harm is critical in this cohort. This article reviews the evidence for and against platelet transfusion in the neonate and identifies areas of future potential neonatal platelet transfusion research.

Benefits of lower neonatal platelet transfusion thresholds

Degree of thrombocytopenia is not a predictor of bleeding risk in neonates, yet most platelet transfusions are given prophylactically in non-bleeding premature infants. Recent data support a lower platelet transfusion threshold of 25 × 109 /L in non-bleeding premature neonates and indicate that higher transfusion thresholds may be associated with harm including increased risk of death and bleeding. The mechanism of increased adverse events with higher platelet transfusion threshold is unknown, but considerations include adult platelets disrupting the neonatal hemostatic balance of hypoactive platelets in a hypercoagulable and fragile environment and having a pro-inflammatory effect.

Implementation of a neonatal platelet transfusion guideline to reduce non-indicated transfusions using a quality improvement framework.

ObjectiveVariation exists in neonatal platelet transfusion practices. Recent studies found potential harm in liberal platelet transfusion practices, supporting the use of lower transfusion thresholds. Our aim was to reduce non-indicated platelet transfusions through implementation of a restrictive platelet transfusion guideline.Study designPlatelet transfusions from January 2017 to December 2019 were classified as indicated or non-indicated using the new guideline. Interventions included guideline implementation and staff education. Outcomes were evaluated using statistical process control charts. Major bleeding was the balancing measure.ResultDuring study, 438 platelet transfusions were administered to 105 neonates. The mean number of non-indicated platelet transfusions/month decreased from 7.3 to 1.6. The rate of non-indicated platelet transfusions per 100 patient admissions decreased from 12.5 to 2.9. Rates of major bleeding remained stable.ConclusionsImplementation of a restrictive neonatal platelet transfusion guideline significantly reduced potentially harmful platelet transfusions in our NICU without a change in major bleeding.

Severity of Thrombocytopenia at the Time of Platelet Transfusion Influences Post-Transfusion Platelet Kinetics and the Effects of Platelets on Plasma Cytokines in a Model of Murine Neonatal Sepsis

Thrombocytopenia affects 20-30% of neonates admitted to the Neonatal Intensive Care Unit (NICU) and up to 70% of those born extremely prematurely, with sepsis being one of the most frequent causes. Since preterm neonates also have a high bleeding risk, it has been widely accepted that they should receive platelet transfusions at higher platelet count (PC) thresholds than older children or adults. However, there is no consensus regarding what the appropriate threshold should be, particularly in critically ill infants. Surveys and observational studies have revealed extraordinary world-wide variability in neonatal platelet transfusion thresholds, with North-American neonatologists typically using more liberal thresholds (i.e. PC&amp;lt;100x109/L) than European neonatologists. Here we hypothesized that the severity of thrombocytopenia at the time of platelet transfusion would influence the post-transfusion platelet kinetics and the effects of platelets on the inflammatory response of septic newborn mice. To test these hypotheses, we used a validated model of neonatal sepsis/peritonitis, consisting of injecting cecal slurry (CS) or 15% glycerol (control) IP into post-natal day 10 (P10) mice. The CS dose used in these studies induced severe sepsis with a high mortality. c-MPL KO pups (which lack the TPO receptor, pre-infection PC 92±38 x 103/µL) and WT B6 pups (pre-infection PC 748±169 x 103/µL) were used to model severe and mild thrombocytopenia at the time of transfusion, respectively. Two hours after infection, mice from both genotypes were transfused with washed platelets from adult GFP mice (5x107platelets/gram) or with Tyrode's buffer. PCs and GFP% were measured by flow cytometry 2 and 22 hrs post-transfusion. At 2 hours, as expected, transfused septic mice of both genotypes had higher PCs than non-transfused septic littermates (217±118 vs 24±9 x103/µL for c-MPLKO mice, p&amp;lt;0.0001, and 764±193 vs. 549±155 x103/µL for WT mice, p&amp;lt;0.01). By 22 hours post-transfusion, transfused septic c-MPL KO mice still had significantly higher PCs than their non-transfused septic littermates (127±71 vs. 21±12 x103/µL, p&amp;lt;0.01; n=7 per group), but there were no significant differences between transfused and non-transfused septic WT mice (415±139 vs. 310±113 x 103/µL, p=0.1;n=7 per group). Between 2 and 22 hrs post-transfusion, PCs dropped at a nearly three-fold higher rate in transfused septic WT mice than in transfused septic c-MPL KO mice (by 17±8 vs. 6±5 x103 platelets/µL/h). In that interval, adult transfused platelets (GFP+) decreased by a larger percentage than neonatal platelets (GFP-) in transfused septic mice of both genotypes (by 64±14% vs. 46±21% in WT mice, and by 53±27% vs. 28±28% in c-MPL KO mice, both p&amp;lt;0.01), although these observations don't account for ongoing neonatal platelet production. Examination of a panel of plasma cytokines 24h after infection revealed significantly increased levels of pro-inflammatory (IL-6, TNF-alpha, and MCP-1) and anti-inflammatory (IL-10) cytokines in non-transfused septic neonates of both genotypes, compared to controls. Interestingly, platelet transfusions significantly reduced the levels of these cytokines in septic WT mice compared to non-transfused littermates, but had no effect on the cytokine levels of septic c-MPLKO mice. Platelets have been recently shown to reduce TNF-alpha production by murine macrophages at high LPS concentrations (Xiang, 2013) and to sequester both pro- and anti-inflammatory cytokines released by monocytes in response to LPS (Carestia, 2019). Our findings suggest that, in neonatal sepsis, this might require PCs to be above a certain threshold. The consequences of these differences on the outcomes of neonatal sepsis are being investigated. Disclosures Stowell: Grifols: Honoraria. Sola-Visner:Sysmex America, Inc.: Other: Laboratory equipment on loan, Research Funding.

Platelet transfusion thresholds in neonatal medicine

Thrombocytopenia is common in preterm neonates. Thresholds for prophylactic platelet transfusion vary widely due to lack of evidence. The results of the PlaNet-2/MATISSE Study identified harm in the form of mortality and major bleed in babies prophylactically transfused below a platelet count of 50 × 109/L compared to 25 × 109/L. Neonatal platelet transfusions are administered at volumes based on historical practice which greatly exceed those routinely used in adults. Rate of transfusion is also based around practice in trauma and does not take into account the physiology of the preterm infant. There are multiple ways in which platelets may be mediating harm and this review discusses these potential mechanisms including immunological, inflammatory and blood group incompatibility. Much of the difficulty in assessing harm relates to problems in classification of transfusion-associated adverse events in babies. Thrombocytopenia and timing, efficacy and adverse effects of platelet transfusion are poorly understood. Further research is essential.

Platelet transfusions in neonates.

Journal of Paediatrics and Child HealthVolume 55, Issue 6 p. 726-726 Heads Up Platelet transfusions in neonates First published: 02 June 2019 https://doi.org/10.1111/jpc.14452 edited by Craig Mellis (craig.mellis@sydney.edu.au) Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume55, Issue6June 2019Pages 726-726 RelatedInformation

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age <34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count <50x109/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions. The study was registered at www.clinicaltrials.gov (NCT03110887).

Transfusion practice in neonates.

Neonates, especially extremely low birth weight infants, are among the groups of patients undergoing transfusion frequently. Since they are exposed to higher specific transfusion risks compared to the patients of other age groups, there are many special aspects that must be considered for transfusion therapy in neonates. The transfusion risks in neonates include adverse outcomes specific for preterm infants as well as increased metabolic, immunologic, and infectious complications. To reduce the risks of transfusion-transmitted cytomegalovirus infection and transfusion-associated graft-versus-host disease, leukoreduced and irradiated cellular blood products should be used for all neonates. This review summarizes the risks of neonatal transfusion therapy, specific methods to reduce risk, and current trends and practices of red blood cell and platelet transfusions in neonates, to facilitate decision-making for neonatal transfusion.

Neonatal Platelet Transfusions and Future Areas of Research.

Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence-based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom thrombocytopenia is common. Their unique physiology and associated complications make the risks and benefits of platelet transfusions difficult to understand. The goal of this review was to highlight research areas that need to be addressed to better understand the risks and benefits of platelet transfusions in neonates. Specifically, it will be important to identify neonates at risk of bleeding who would benefit from a platelet transfusion and to determine whether platelet transfusions either abrogate or exacerbate common neonatal complications such as sepsis, chronic lung disease, necrotizing enterocolitis, and retinopathy of prematurity.

Red cell and platelet transfusions in neonates: a population-based study

ObjectivesThis study aimed to describe the use of red cells, platelets and exchange transfusions among all neonates in a population cohort, to examine trends in transfusion over time and to...

Neonatal platelets: mediators of primary hemostasis in the developing hemostatic system.

The human hemostatic system is developmentally regulated, resulting in qualitative and quantitative differences in the mediators of primary and secondary hemostasis as well as fibrinolysis in neonates and infants. Although gestational age-related differences in coagulation factor levels occur, the existence of a unique neonatal platelet phenotype remains controversial. Complicated by difficulties in obtaining adequate neonatal blood volumes with which to perform functional assays, ambiguity surrounds the characterization of neonatal platelets. Thus, much of the current knowledge of neonatal platelet function has been based on studies from cord blood samples. Studies suggest that cord blood-derived platelets, as a surrogate for neonatal platelets, are hypofunctional when compared with adult platelets. This relative platelet dysfunction, combined with a propensity toward thrombocytopenia in the neonatal intensive care unit population, creates a clinical conundrum regarding the appropriate administration of platelet transfusions. This review provides an appraisal of the distinct functional phenotype of neonatal platelets. Neonatal platelet transfusion practices and the impact of the relatively hypofunctional neonatal platelet on those practices will be considered.

Platelets for Neonatal Transfusion - Study 2: A Randomised Controlled Trial to Compare Two Different Platelet Count Thresholds for Prophylactic Platelet Transfusion to Preterm Neonates

Introduction: Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia. Objectives: Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28. Methods: PlaNeT-2 is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised to receive prophylactic platelet transfusions to maintain platelet counts at or above either 25 × 10⁹/l or 50 × 10⁹/l. The primary outcome measure is the proportion of patients who either die or experience a major bleed up to and including study day 28. A total of 660 infants will be randomised. Results and Conclusions: This trial will help define optimal platelet transfusion support for severely thrombocytopenic preterm neonates by evaluating the risks and benefits of two different prophylactic neonatal platelet transfusion thresholds.