Reduced platelet function in preterm neonates compared with term neonates

Hovgesen, Nadia Thrane; Hviid, Claus Vinter Bødker; Grevsen, Alexander K.; Hansen, Anne R.; Hvas, Anne‐Mette

doi:10.1002/rth2.12751

Cited by 5 publications

(3 citation statements)

References 54 publications

(157 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, neonatal platelets were found to be hyperresponsive to the platelet inhibitor PGE1, also contributing to the reduced responsiveness. 31 , 33 , 34 , 35 More recent studies have shown distinct platelet hyporeactivity upon immunoreceptor and GPCR stimulation 36 , 37 and have discussed reduced G 12 /G 13 expression as a causative factor for reduced δ-granule secretion. 38 These controversial findings could be explained by the heterogeneous study design regarding readouts (granule release, GPIIb/IIIa activation, aggregometry, and electron microscopy), the material used (peripheral vs umbilical blood), time points, or the respective control group (adults vs infants).…”

Section: Discussionmentioning

confidence: 99%

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

Weiss¹,

Drayss

Mott

et al. 2023

Blood Advances

View full text Add to dashboard Cite

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, mainly reflected by stage-specific expression of hemoglobin chains. Perinatal alterations of thrombopoiesis remain poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adults. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks) and 10 term neonates, 8 infants (<2a), 5 children (2-13a) and 9 adults (>13a). Blood was withdrawn at up to 3 different time points in neonates (t1: 0-2, t2: 3-7, and t3: 8-14 days after birth). We found that expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced, but correlated with decreased platelet size indicating a normal surface density. While CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP or U46619 was unaltered or just slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted, but showed a continuous increase until adulthood, correlating with expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis by automated clustering revealed that neonates presented with a CD63+/PAC1- pattern, followed by a continuous increase of CD63+/PAC-1+ platelets until adulthood. Our findings reveal that the number of platelet-monocyte and -neutrophil aggregates, but not platelet-lymphocyte aggregates is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that platelet phenotype and function evolve continuously from neonates until adulthood.

show abstract

Section: Discussionmentioning

confidence: 99%

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

Weiss¹,

Drayss

Mott

et al. 2023

Blood Advances

View full text Add to dashboard Cite

show abstract

“…102,117,118 Neonatal platelets have distinct in vitro patterns of reactivity when compared to adult platelets but are generally hyporeactive to many activating agonists in vitro. [69][70][71][72][119][120][121][122] Although this might suggest that neonates are at greater bleeding risk compared to adults, reduced platelet reactivity is offset in vivo by compensatory hemostatic mechanisms such as higher hematocrit and circulating von Willebrand Factor levels resulting in a net effect of enhanced primary hemostasis compared to adults. It is unclear whether there is an association between 'adult' platelet transfusions in neonates and thrombosis, as there are currently no robust datasets available to assess this.…”

Section: Specification and Administration Of Platelet Componentsmentioning

confidence: 99%

How I diagnose and treat neonatal thrombocytopenia

Stanworth

Mumford

2023

Blood

View full text Add to dashboard Cite

Neonatal thrombocytopenia defined as the presence of a circulating platelet count <150x109/L is a common abnormality in babies admitted to Neonatal Intensive Care Units. Thrombocytopenia that is typically mild and self-limiting often accompanies neonatal stress in scenarios such as premature delivery or intrauterine growth restriction. However, the differential diagnosis of neonatal thrombocytopenia is wide and includes potential life-threatening disorders such as bacterial sepsis, viral infection and necrotizing enterocolitis. Distinguishing these causes of thrombocytopenia from entities such as genetic thrombocytopenia and fetal and neonatal alloimmune thrombocytopenia is critical for the accurate quantitation of significant adverse events such as intracranial bleeding and for the selection of treatments such as platelet transfusion. In this review, we focus on common differential diagnoses of neonatal thrombocytopenia and highlight how the landscape of diagnosis and management is changing with recent advances in genomic technology and the completion of pivotal clinical trials of platelet transfusion practice. Increasing evidence highlights the need for judicious and restrictive use of platelet transfusions in neonates.

show abstract

“…42 The past three decades have seen considerable advances in flow cytometry analysis, platelet activation analyses, and further characterization of platelets signaling pathways, as summarized by Ramström et al 42 The analysis uses only a small sample volume which makes investigations possible even in premature newborns. 43 However, the analysis is highly specialized, requires highly skilled technicians, and the subsequent interpretation of results is also demanding. Researchers of today are still working to develop flow cytometry for platelet investigations and to standardize the analysis.…”

Section: Platelet Activationmentioning

confidence: 99%

Crucial Stepping Stones in Platelet History

Hvas

2022

Semin Thromb Hemost

View full text Add to dashboard Cite

This review summarizes the time that has passed from the initial registration of the cells that turned out to be platelets up to today's advanced methodologies in platelet investigation. The first reports of “granular masses” appeared in the 1840s, but these “granular masses” remained an unsolved mystery until the 1870s. The breakthrough came in the 1873–1882 period. The cells that later turned out to be platelets were further identified by the German Professor Max Schultze, and later by Osler, who described their disk-like structure. These initial descriptions of platelets were expanded by impressive studies performed by the Italian Pathologist Bizzozero who uncovered the anatomy of platelets and described their role, first in experimental thrombosis and later in the clotting process. Nearly 20 years later, in 1906, Wright published the discovery of megakaryocytes as platelet precursors. Shortly thereafter, the clinical proof of concept illustrating the pivotal role of platelets in arresting bleeding was revealed by Duke who introduced the bleeding time test, also in this period. To investigate platelet function more specifically, light transmission aggregometry was introduced in 1962 and remains the gold standard today. This method inspired the development of several devices employing whole blood using different principles for evaluating platelet function. As of today, flow cytometry is the most advanced method and holds promise to provide new insights into platelet activation. Additionally, advances in genetic testing by the use of next-generation sequencing will allow further improvement of our ability to diagnose inherited platelet disorders.

show abstract

Reduced platelet function in preterm neonates compared with term neonates

Cited by 5 publications

References 54 publications

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

How I diagnose and treat neonatal thrombocytopenia

Crucial Stepping Stones in Platelet History

Contact Info

Product

Resources

About