Why might cord blood be a better source of platelets for transfusion to neonates?

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.

Two-year outcomes following a randomised platelet transfusion trial in preterm infants.

OBJECTIVE: Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN: Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING: 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS: 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×109/L. INTERVENTIONS: Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). MAIN OUTCOMES MEASURES: Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS: Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS: Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER: ISRCTN87736839.

Survey of transfusion practices in preterm infants in Europe.

BACKGROUND: Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. METHODS: From October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries. RESULTS: Responses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. CONCLUSIONS: Transfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Changes in the Use of Fresh-Frozen Plasma Transfusions in Preterm Neonates: A Single Center Experience.

The aim of this study was to evaluate changes in the use of fresh-frozen plasma (FFP) transfusions and the use of clotting tests in preterm neonates in our center over the past two decades. In this retrospective cohort analysis, we included all consecutive neonates with a gestational age at birth between 24 + 0 and 31 + 6 weeks admitted to our neonatal intensive care unit (NICU) between 2004 and 2019. We divided all included neonates into three consecutive time epochs according to date of birth: January 2004 to April 2009, May 2009 to August 2014 and September 2014 to December 2019. The main outcomes were the use of FFP transfusion, coagulation testing and the indications for FFP transfusion. The percentage of preterm neonates receiving FFP transfusion decreased from 5.7% (47/824) to 3.7% (30/901) to 2.0% (17/852) from the first epoch to the last epoch (p < 0.001). Additionally, the rate of neonates undergoing coagulation testing decreased from 24.3% (200/824) to 14.5% (131/901) to 8% (68/852) over the epochs (p < 0.001). Most FFP transfusions were prescribed prophylactically based on prolongation of activated partial thromboplastin time (aPTT) or prothrombin time (PT) (56%). In conclusion, both the use of FFP transfusions and the use of coagulation tests decreased significantly over the years. The majority of the FFP transfusions were administrated prophylactically for abnormal coagulation tests.

Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors.

OBJECTIVES: Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. STUDY DESIGN: A cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis. RESULTS: Sepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0-7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality. CONCLUSIONS: Thrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

Loneliness in Children and Adolescents With Chronic Physical Conditions: A Meta-Analysis.

Objective: This meta-analysis examines loneliness in children and adolescents with chronic physical conditions as compared with their peers. Multilevel meta-analyses were performed on 43 studies (69 samples), published between 1987 and 2015. A total of 2,518 individuals with chronic physical conditions and 1,463 control peers were included in the analyses. Children and adolescents with chronic conditions are, on average, somewhat lonelier than their peers without such conditions. Moreover, the link between chronic conditions and loneliness varied according to the recruitment procedure used for participant selection. Stronger links were found for studies that recruited from patient organizations as compared with clinical registers. Findings support the link between loneliness and chronic conditions. To take into account the heterogeneity within patient groups, we advocate an alternative approach that cuts across diagnostic boundaries and focuses on illness-related variables such as illness duration and visibility of the condition.