The neonatal hemostatic system is different from that of adults. The differences in levels of procoagulant and anticoagulant factors and the evolving equilibrium in secondary hemostasis during the transition from fetal/neonatal life to infancy, childhood, and adult life are known as "developmental hemostasis." In regard to primary hemostasis, while the number (150,000-450,000/µl) and structure of platelets in healthy neonates closely resemble those of adults, there are significant functional differences between neonatal and adult platelets. Specifically, platelets derived from both cord blood and neonatal peripheral blood are less reactive than adult platelets to agonists, such as adenosine diphosphate (ADP), epinephrine, collagen, thrombin, and thromboxane (TXA2) analogs. This platelet hyporeactivity is due to differences in expression levels of key surface receptors and/or in signaling pathways, and is more pronounced in preterm neonates. Despite these differences in platelet function, bleeding times and PFA-100 closure times (an in vitro test of whole-blood primary hemostasis) are shorter in healthy full-term infants than in adults, reflecting enhanced primary hemostasis. This paradoxical finding is explained by the presence of factors in neonatal blood that increase the platelet-vessel wall interaction, such as high von Willebrand factor (vWF) levels, predominance of ultralong vWF multimers, high hematocrit, and high red cell mean corpuscular volume. Thus, the hyporeactivity of neonatal platelets should not be viewed as a developmental deficiency, but rather as an integral part of a developmentally unique, but well balanced, primary hemostatic system. In clinical practice, due to the high incidence of bleeding (especially intraventricular hemorrhage, IVH) among preterm infants, neonatologists frequently transfuse platelets to non-bleeding neonates when platelet counts fall below an arbitrary limit, typically higher than that used in older children and adults. However, recent studies have shown that prophylactic platelet transfusions not only fail to decrease bleeding in preterm neonates, but are associated with increased neonatal morbidity and mortality. In this review, we will describe the developmental differences in platelet function and primary hemostasis between neonates and adults, and will analyze the implications of these differences to platelet transfusion decisions.

Neonatal platelet physiology and implications for transfusion.

Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated.

Proposing a care practice bundle for neonatal encephalopathy during therapeutic hypothermia

How I diagnose and treat neonatal thrombocytopenia.

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.

https://www.mdpi.com/2077-0383/9/11/3789/pdf

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

Non-immune thrombocytopenia is caused by multiple pathologies; the most common causes are extra- or intrauterine infections, whereas secondary cases result from other pathologies involved in the fetal-placentalmaternal interface. This second article lists its causes and provides details of the different pathologies. Platelet transfusion is widely used in neonatology, both as treatment and as bleeding prophylaxis. However, there is no general consensus about the platelet count threshold that is convenient to indicate a transfusion or actual indications. Recent articles are commented regarding the different proposed strategies. The emphasis is on discussing the multiple adverse effects of platelet transfusions because knowledge about them is changing the paradigm for indications, suggesting that a much more restrictive policy is required.

/pdf/neonatal-thrombocytopenia-a-review-ii-non-immune-3jv6qc4bjc.pdf

Neonatal thrombocytopenia: A review. II. Non-immune thrombocytopenia; platelet transfusion.

Neonatal Platelet Transfusions: Starting Again.

Platelet transfusion thresholds in neonatal medicine

Neonatal encephalopathy (NE) is associated with abnormality of neurological function and involves multiorgan dysfunction. There are long-term complications such as cerebral palsy and developmental delay. Cardiac, renal, neurological and other organ dysfunctions are well described. Haematological dysfunction is relatively common and includes anaemia, thrombocytopenia, monocyte and neutrophil activation, hypofibrinogenemia and coagulopathy. There is a lack of consensus definitions of hematological parameters and optimal levels for intervention due to the lack of interventional studies in term neonates and the lack of knowledge of the optimal values during therapeutic hypothermia. However, derangements in hematological values are also associated with neurodevelopmental outcomes. This article outlines the different hematological complications associated with NE and therapeutic hypothermia and suggests a framework for management.

Haematological issues in neonates with neonatal encephalopathy treated with hypothermia

Background: Down's syndrome (DS) is the most common chromosomal abnormality globally. Ireland has one of the highest rates of DS in the western world with an incidence of 1:444 live births. Congenital heart disease (CHD) and pulmonary hypertension (PH) are the commonest morbidities affecting the cardiovascular system in DS. PH is associated with significant morbidity and an increase risk of mortality. The impact of the diagnosis of DS, the presence of CHD and the associated PH on myocardial function during transition and over the first 2 years of age in this population is not well defined and warrants further study. In particular, serial measurements of pulmonary pressures in this population over the first week of age are lacking. This study aims to characterise myocardial function and pulmonary haemodynamics in infants with Down syndrome during the transitional period (over the first week of age) and throughout the first two years of age. Methods: A prospective, observational study utilising novel echocardiography techniques to assess myocardial function and pulmonary haemodynamics over the first two years of age in infants with Down Syndrome. A population of healthy infants without CHD or a diagnosis of DS will be recruited as controls. This study will be conducted across the three Dublin maternity units. Discussion: In total, 70 babies with DS have been enrolled into this study with 292 echocardiograms performed to date. Further evaluation of cardiac performance in DS infants with and without CHD may yield more insight into the pathophysiology of cardiac dysfunction and pulmonary hypertension that are recognised features in these patients. This could aid in our ability to monitor and treat patients, as well as improve our ability to predict outcomes.

Longitudinal assessment of cardiac function in infants with Down's syndrome using novel echocardiography techniques - project protocol

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Papers

Neonatal Platelet Transfusions: Starting Again.

Platelet transfusion thresholds in neonatal medicine

Haematological issues in neonates with neonatal encephalopathy treated with hypothermia

Longitudinal assessment of cardiac function in infants with Down's syndrome using novel echocardiography techniques - project protocol