OBJECTIVE: Despite lack of evidence supporting efficacy, prophylactic fresh frozen plasma and Octaplas transfusions may be administered to very preterm infants to reduce bleeding risk. International variation in plasma transfusion practices in neonatal intensive care units (NICUs) is poorly understood, therefore, we aimed to describe neonatal plasma transfusion practice in Europe. DESIGN: Prospective observational study. SETTING: 64 NICUs in 22 European countries, with a 6-week study period per centre between September 2022 and August 2023. PATIENTS: Preterm infants born below 32 weeks of gestational age. INTERVENTIONS: Admission to the NICU. MAIN OUTCOME MEASURES: Plasma transfusion prevalence, cumulative incidence, indications, transfusion volumes and infusion rates and adverse effects. RESULTS: A total of 92 of 1143 infants included (8.0%) received plasma during the study period, collectively receiving 177 transfusions. Overall prevalence was 0.3 plasma transfusion days per 100 admission days, and rates varied substantially across Europe. By day 28 of life, 13.5% (95% CI 10.0% to 16.9%) of infants received at least one plasma transfusion, accounted for competing risks of death or discharge. Transfusions were given for a broad range of indications, including active bleeding (29.4%), abnormal coagulation screen results (23.7%) and volume replacement/hypotension (21.5%). Transfusion volumes and infusion rates varied significantly; the most common volume was 15 mL/kg (range: 5-30 mL/kg) and the most common duration was 2 hours (range: 30 min to 6 hours). CONCLUSIONS: We found wide variation in plasma transfusion practices in Europe, highlighting the need for evidence to inform neonatologists in daily practice and guidelines, in particular for non-bleeding indications. TRIAL REGISTRATION NUMBER: ISRCTN17267090.

2 Department of Neonatology Poznan University of Medical Sciences Poznan Poland

Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands

Department of Molecular and Cellular Hemostasis Sanquin Research Amsterdam The Netherlands

Department of Neonatology Charité Universitätsmedizin Berlin Berlin Germany

Department of Neonatology La Fe University Hospital Valencia Spain

Department of Neonatology Semmelweis University Budapest Hungary

Department of Neonatology Universitair Ziekenhuis Leuven Leuven Belgium

Department of Neonatology University Children's Hospital University Medical Centre Ljubljana Ljubljana Slovenia

Department of Neonatology University College Dublin Dublin Ireland

Department of Neonatology University of Medicine and Pharmacy Iuliu Hatieganu Cluj Napoca Romania

Department of Neonatology University of Zurich Zurich Switzerland

Department of Pediatrics Centre Hospitalier Universitaire de Rennes Rennes France

Department of Pediatrics University Hospital Centre Zagreb Zagreb Croatia

Department of Pediatrics University Hospital Hradec Kralove Hradec Kralove Czech Republic

Division of Neonatology Medical University of Vienna Vienna Austria

Division of Neonatology Willem Alexander Children's Hospital Leiden University Medical Center Leiden The Netherlands

Faculty of Health Sciences University of Bristol Bristol UK

Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Fondazione IRCCS Policlinico San Matteo Pavia Italy

Jessenius Faculty of Medicine Department of Neonatology University Hospital Martin Martin Slovakia

Karolinska Institute Stockholm Sweden

National Perinatal Epidemiology Unit Oxford Population Health University of Oxford Oxford UK

Neonatal Department Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Neonatology National Maternity Hospital Dublin Ireland

NHS Blood and Transplant London UK

Paediatric Clinic University Medical Center Sarajevo Sarajevo Bosnia and Herzegovina

Pediatric Hematology Emma Children's Hospital Amsterdam UMC Locatie AMC University of Amsterdam Amsterdam The Netherlands

Sanquin Research Sanquin Blood Supply Foundation Amsterdam The Netherlands

Unidade Local de Saúde de Santo António Centro Materno Infantil do Norte Porto Portugal

University of Oxford Oxford UK

Women and Children's Division Department of Neonatal Intensive Care Oslo University Hospital Oslo Norway

Zobrazit více v PubMed

Sokou R, Parastatidou S, Konstantinidi A, et al. Fresh frozen plasma transfusion in the neonatal population: A systematic review. Blood Rev. 2022;55:100951. doi: 10.1016/j.blre.2022.100951. PubMed DOI

Keir AK, Stanworth SJ. Neonatal Plasma Transfusion: An Evidence-Based Review. Transfus Med Rev. 2016;30:174–82. doi: 10.1016/j.tmrv.2016.07.001. PubMed DOI

New HV, Berryman J, Bolton-Maggs PHB, et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol. 2016;175:784–828. doi: 10.1111/bjh.14233. PubMed DOI

Motta M, Del Vecchio A, Perrone B, et al. Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study. Arch Dis Child Fetal Neonatal Ed. 2014;99:F303–8. doi: 10.1136/archdischild-2013-304747. PubMed DOI

Stanworth SJ, Grant-Casey J, Lowe D, et al. The use of fresh-frozen plasma in England: high levels of inappropriate use in adults and children. Transfusion. 2011;51:62–70. doi: 10.1111/j.1537-2995.2010.02798.x. PubMed DOI

Elbourne D, The Northern Neonatal Nursing Initiative [NNNI] Trial Group A randomized trial comparing the effect of prophylactic intravenous fresh frozen plasma, gelatin or glucose on early mortality and morbidity in preterm babies. Eur J Pediatr . 1996;155:580–8. doi: 10.1007/BF01957909. PubMed DOI

Randomised trial of prophylactic early fresh-frozen plasma or gelatin or glucose in preterm babies: outcome at 2 years. Lancet. 1996;348:229–32. doi: 10.1016/S0140-6736(95)12506-X. PubMed DOI

Motta M, Guaragni B. Fresh Frozen Plasma Administration in the NICU: Evidence-based Guidelines. Curr Pediatr Rev. 2023;19:342–51. doi: 10.2174/1573396319666221219153009. PubMed DOI

Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72:1651–7. PubMed

Neary E, McCallion N, Kevane B, et al. Coagulation indices in very preterm infants from cord blood and postnatal samples. J Thromb Haemost. 2015;13:2021–30. doi: 10.1111/jth.13130. PubMed DOI

Christensen RD, Baer VL, Lambert DK, et al. Reference intervals for common coagulation tests of preterm infants (CME) Transfusion. 2014;54:627–32. doi: 10.1111/trf.12322. PubMed DOI

Roberts JC, Javed MJ, Lundy MK, et al. Characterization of laboratory coagulation parameters and risk factors for intraventricular hemorrhage in extremely premature neonates. J Thromb Haemost. 2022;20:1797–807. doi: 10.1111/jth.15755. PubMed DOI PMC

Scrivens A, Reibel NJ, Heeger L, et al. Survey of transfusion practices in preterm infants in Europe. Arch Dis Child Fetal Neonatal Ed. 2023;108:360–6. doi: 10.1136/archdischild-2022-324619. PubMed DOI PMC

Houben NAM, Fustolo-Gunnink S, Fijnvandraat K, et al. Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023. JAMA Netw Open. 2024;7:e2434077. doi: 10.1001/jamanetworkopen.2024.34077. PubMed DOI PMC

Houben NAM, Lopriore E, Fijnvandraat K, et al. Platelet transfusion in neonatal intensive care units of 22 European countries: a prospective observational study. Lancet Reg Health Eur . 2024;47:101086. doi: 10.1016/j.lanepe.2024.101086. PubMed DOI PMC

Stijnen T, Hamza TH, Ozdemir P. Random effects meta-analysis of event outcome in the framework of the generalized linear mixed model with applications in sparse data. Stat Med. 2010;29:3046–67. doi: 10.1002/sim.4040. PubMed DOI

Puetz J, Darling G, McCormick KA, et al. Fresh frozen plasma and recombinant factor VIIa use in neonates. J Pediatr Hematol Oncol. 2009;31:901–6. doi: 10.1097/MPH.0b013e3181c29c25. PubMed DOI

Altuntas N, Yenicesu I, Beken S, et al. Clinical use of fresh-frozen plasma in neonatal intensive care unit. Transfus Apher Sci. 2012;47:91–4. doi: 10.1016/j.transci.2012.05.007. PubMed DOI

Keir AK, Yang J, Harrison A, et al. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks’ gestation in Canada. Transfusion. 2015;55:1340–6. doi: 10.1111/trf.12998. PubMed DOI

Houben NAM, Heeger LE, Stanworth SJ, et al. Changes in the Use of Fresh-Frozen Plasma Transfusions in Preterm Neonates: A Single Center Experience. J Clin Med. 2020;9:3789. doi: 10.3390/jcm9113789. PubMed DOI PMC

Pavenski K, Stanworth S, Fung M, et al. Quality of Evidence-Based Guidelines for Transfusion of Red Blood Cells and Plasma: A Systematic Review. Transfus Med Rev. 2018 doi: 10.1016/j.tmrv.2018.05.004. PubMed DOI

Davenport P, Sola-Visner M. Hemostatic Challenges in Neonates. Front Pediatr. 2021;9:627715. doi: 10.3389/fped.2021.627715. PubMed DOI PMC

Pichler E, Pichler L. The neonatal coagulation system and the vitamin K deficiency bleeding - a mini review. Wien Med Wochenschr. 2008;158:385–95. doi: 10.1007/s10354-008-0538-7. PubMed DOI

Tripodi A, Ramenghi LA, Chantarangkul V, et al. Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests. Haematologica. 2008;93:1256–9. doi: 10.3324/haematol.12566. PubMed DOI

Yang L, Stanworth S, Hopewell S, et al. Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion. 2012;52:1673–86. doi: 10.1111/j.1537-2995.2011.03515.x. PubMed DOI

Müller MCA, Straat M, Meijers JCM, et al. Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost. 2015;13:989–97. doi: 10.1111/jth.12908. PubMed DOI

Curley A, Stanworth SJ, Willoughby K, et al. Randomized Trial of Platelet-Transfusion Thresholds in Neonates. N Engl J Med. 2019;380:242–51. doi: 10.1056/NEJMoa1807320. PubMed DOI

Fustolo-Gunnink SF, Roehr CC, Lieberman L, et al. Platelet and red cell transfusions for neonates: lifesavers or Trojan horses? Expert Rev Hematol. 2019;12:797–800. doi: 10.1080/17474086.2019.1657824. PubMed DOI

Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;67:1–8. doi: 10.1203/PDR.0b013e3181c1b176. PubMed DOI PMC

Sokou R, Parastatidou S, Konstantinidi A, et al. Bleeding Scoring Systems in Neonates: A Systematic Review. Semin Thromb Hemost. 2024;50:620–37. doi: 10.1055/s-0043-1777070. PubMed DOI

Oca MJ, Nelson M, Donn SM. Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension. J Perinatol. 2003;23:473–6. doi: 10.1038/sj.jp.7210971. PubMed DOI

Emery EF, Greenough A, Gamsu HR. Randomised controlled trial of colloid infusions in hypotensive preterm infants. Arch Dis Child. 1992;67:1185–8. doi: 10.1136/adc.67.10_spec_no.1185. PubMed DOI PMC

Osborn DA, Evans N. Early volume expansion for prevention of morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2004;2004:CD002055. doi: 10.1002/14651858.CD002055.pub2. PubMed DOI PMC

Eiby YA, Lingwood BE, Wright IMR. Plasma Leak From the Circulation Contributes to Poor Outcomes for Preterm Infants: A Working Hypothesis. Front Neurol. 2021;12:636740. doi: 10.3389/fneur.2021.636740. PubMed DOI PMC

Uhing MR. The albumin controversy. Clin Perinatol. 2004;31:475–88. doi: 10.1016/j.clp.2004.03.018. PubMed DOI

Saadah NH, van der Bom JG, Wiersum‐Osselton JC, et al. Comparing transfusion reaction risks for various plasma products – an analysis of 7 years of ISTARE haemovigilance data. Br J Haematol. 2018;180:727–34. doi: 10.1111/bjh.15082. PubMed DOI

Basavarajegowda A, Plakkal N. Transfusion reactions in neonates and pediatrics: How and why are they different. Asian J Transfus Sci. 2023;17:97–102. doi: 10.4103/ajts.ajts_27_22. PubMed DOI PMC

Henricks LM, Huisman EJ, Lopriore E, et al. Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate—Preventable by using solvent/detergent‐treated pooled plasma? Transfus Med. 2023;33:174–8. doi: 10.1111/tme.12926. PubMed DOI

Belderbos ME, Levy O, Meyaard L, et al. Plasma‐mediated immune suppression: a neonatal perspective. Pediatric Allergy Immunology. 2013;24:102–13. doi: 10.1111/pai.12023. PubMed DOI

Peñas-Martínez J, Barrachina MN, Cuenca-Zamora EJ, et al. Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults. Int J Mol Sci. 2021;22:1926. doi: 10.3390/ijms22041926. PubMed DOI PMC