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 25×10$^{9}$/L in non-bleeding infants of GA of <28 weeks, while the 25×10$^{9}$/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

Neonatal thrombocytopenia : from bleeding risk to new therapies on the horizon

Background: Thrombocytopenia is common in the Neonatal Intensive Care Unit and if severe, it is treated with platelet transfusions to prevent bleeding. Previous studies found a weak correlation between thrombocytopenia and incidence of bleeding. The poor predictive value of the platelet count has highlighted the need for better tests to assess bleeding risk and to guide transfusion decisions. Romiplostim (ROM) and eltrombopag (ELT) – two thrombopoietin (TPO) mimetics approved for treatment of thrombocytopenia in adults – may benefit thrombocytopenic neonates by potentially reducing platelet transfusions. Objectives: First, the relationship between platelet count and in vitro bleeding time (PFA- 100 closure times, CTs) in thrombocytopenic neonates was evaluated. Second, other risk factors associated with CTs were determined. Third, the relationship between the PFA-100 CTs and clinical bleeding was assessed. Fourth, in vitro responses of human neonatal vs. adult megakaryocyte (MK) progenitors to TPO, ROM and ELT, were compared. Methods: We conducted a single institution cross-sectional study (Study 1), and a multicenter prospective longitudinal study (Study 2). Blood samples from thrombocytopenic neonates were tested with PFA-100 to measure in vitro bleeding time. In addition to platelet counts, other variables including severity of illness were obtained. Bleedings were quantified using the Neonatal Bleeding Assessment Tool (NeoBAT). In a pre-clinical study (Study 3), hematopoietic progenitor (CD34+) cells isolated from umbilical cord blood (CB) and adult peripheral blood (PB) were cultured in escalating concentrations of TPO, ROM, or ELT. After 14 days, the number of MKs and their maturation (CD42b expression) and ploidy were evaluated by flow cytometry. Results: In Study 1, we found that all infants with platelet counts >90x109/L had normal CT- ADPs. At platelet counts <90x109/L, 74 % (14/19) of the infants had normal or minimally prolonged CT-ADPs, while 16 % (3/19) had markedly prolonged values. Study 2 showed that in preterm infants with gestational age <27 weeks and platelet counts <100×109/L, CT-ADP but not platelet counts was associated with NeoBAT scores. This association was robust also after adjustment for demographic and clinical variables. Study 3 found that with escalating concentrations of TPO, ROM, or ELT, CB progenitors generated 10 times more MKs than PB-MKs. At low concentrations, ELT stimulated megakaryopoiesis, but at high concentrations, ELT suppressed MK differentiation and proliferation via its intracellular iron chelating properties. Conclusions: The CT-ADP test (an in vitro test of whole blood primary hemostasis) is a significantly better marker of bleeding risk than platelet counts among thrombocytopenic preterm neonates. TPO mimetics increased the numbers of cord blood MKs but did not influence their maturation or ploidy level. ELT generated fewer MKs than TPO or ROM. At low concentrations ELT stimulated megakaryopoiesis, but higher concentrations resulted in reduced MK differentiation and proliferation. These findings may have implications for the management of thrombocytopenic infants