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      Platelet transfusions in preterm infants: current concepts and controversies—a systematic review and meta-analysis

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          Abstract

          Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8–3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7–5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3–8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken.

              Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect.

          What is Known:

          • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage .

          • Lack of consensual criteria for transfusion.

          What is New:

          • A significant association between platelet transfusions and mortality, sepsis, and NEC .

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00431-023-05031-y.

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          Most cited references26

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          Randomized Trial of Platelet-Transfusion Thresholds in Neonates

          Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia.
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            Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system.

            Thrombocytopenia is common in neonatal intensive care units (NICU), with 18 to 35% of patients developing this problem before hospital discharge. It might be even more common among extremely low birth weight neonates (ELBW, < or = 1000 g birth weight). However, little is known about thrombocytopenia in the ELBW population. We sought to determine the incidence, timing, causes, platelet transfusions given, and outcomes of thrombocytopenia among ELBW neonates. We performed a cohort analysis of all 284 ELBW neonates born during 2003 and 2004 cared for in any of the Intermountain Healthcare level III NICUs. Multiple platelet counts were obtained in all 284 (range, 4 to 441 platelet counts/patient). Of the 284, 208 (73%) had one or more platelet counts < or =150 000/microl. Most were detected during the first days of life; 80% were detected during the first week and only 20% were detected thereafter. Thrombcytopenia was more common among the smallest patients; 85% incidence among those < or =800 g, 60% among those 801 to 900 g, and 53% among those 901 to 1000 g. Platelet transfusions were given to 129 of the 208 thrombocytopenic neonates. More than 90% were given prophylactically (the patient was not bleeding). The mortality rate among those that received platelet transfusions was twice that of those that received no platelet transfusions (P < 0.01). In 48% of cases, the cause of the thrombocytopenia went undiagnosed. The most common explanations were being small for gestational age or delivered to a hypertensive mother, DIC, bacterial infection, fungal infection, and necrotizing enterocolitis, respectively. We observed thrombocytopenia among ELBW neonates at a rate more than twice that reported among the general NICU population. Much remains to be discovered about the etiology and best treatments of thrombocytopenia among ELBW neonates.
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              A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.

              A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                filipa.flordelima@gmail.com
                Journal
                Eur J Pediatr
                Eur J Pediatr
                European Journal of Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-6199
                1432-1076
                1 June 2023
                1 June 2023
                2023
                : 182
                : 8
                : 3433-3443
                Affiliations
                [1 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Faculty of Medicine, , University of Porto, ; Porto, Portugal
                [2 ]GRID grid.414556.7, ISNI 0000 0000 9375 4688, Department of Pediatrics, , Centro Hospitalar Universitário de São João, ; Porto, Portugal
                [3 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, , University of Porto, ; Porto, Portugal
                [4 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Centre for Health Technology and Services Research, Health Research Network (CINTESIS@RISE), Faculty of Medicine , , University of Porto, ; Porto, Portugal
                [5 ]GRID grid.414556.7, ISNI 0000 0000 9375 4688, Department of Neonatology, , Centro Hospitalar Universitário de São João, Alameda Prof Hernâni Monteiro, ; 4200-319 Porto, Portugal
                [6 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Department of Gynecology-Obstetrics and Pediatrics, Faculty of Medicine, , University of Porto, ; Porto, Portugal
                Author notes

                Communicated by Daniele De Luca

                Author information
                http://orcid.org/0000-0001-6286-3416
                http://orcid.org/0000-0003-1834-3055
                http://orcid.org/0000-0001-9021-1810
                http://orcid.org/0000-0001-6402-3285
                http://orcid.org/0000-0003-1358-0254
                Article
                5031
                10.1007/s00431-023-05031-y
                10460362
                37258776
                01e1dca4-7ce7-458b-aa8b-fa5cd35bfab8
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 April 2023
                : 10 May 2023
                : 17 May 2023
                Funding
                Funded by: Universidade do Porto
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Pediatrics
                platelets,transfusions,preterm,death,sepsis,necrotizing enterocolitis
                Pediatrics
                platelets, transfusions, preterm, death, sepsis, necrotizing enterocolitis

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