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The Effect of Platelets on Thrombin Generation in the Premature Infant: The EVENT Study

C. Murphy1,2, E. Neary3,4, B. Kevane5, D. O'Reilly2, J. O'Loughlin6, A. EL-Khuffash2,1, P. Maguire7, F. NíAinle5,7,8,9, N. McCallion2,1

1Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland, 2Department of Neonatology, Rotunda Hospital, Dublin, Ireland, 3Department of Neonatology, Liverpool Women’s Hospital, Liverpool, United Kingdom, 4Department of Health and Life Sciences, University of Liverpool, Liverpool,, United Kingdom, 5Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland, 6Department of Pathology, Rotunda Hospital, Ireland, Dublin, Ireland, 7UCD Conway SPHERE Research Group, University College Dublin, Dublin, Ireland, 8School of Medicine, University College Dublin, Dublin, Ireland, 9Department of Haematology, Rotunda Hospital, Dublin, Ireland

Abstract Number: OC 20.3

Meeting: ISTH 2021 Congress

Theme: Pediatrics » Bleeding in Neonates and Children

Background: Premature infants are at risk of haemorrhage and have reduced levels of coagulation factor and hypo-reactive platelets. In spite of these recognized changes, plasma thrombin generation (characterized by Calibrated Automated Thrombography (CAT)) in preterm infants, is similar or enhanced compared to term infants.

Aims: To characterize platelet-dependent thrombin generation in premature infants.

Methods: This was a prospective observational study, performed in platelet rich (PRP) and platelet poor (PPP) plasma obtained from umbilical cord blood (PRP: 200 xg x 10 mins; PPP: 3000 RPM x 6 mins x 2). Premature infants (24 – 31 weeks) and term controls were recruited. Using a CAT assay, thrombin generation was stimulated by tissue factor only (final concentration 1pM), rendering the assay dependent upon the phospholipid content of plasma. Hospital ethical approval and parental consent was obtained.

Results: In a preliminary analysis of the first twenty-six patients, no significant differences in CAT parameters in PRP were demonstrated between preterm and term infants (Table 1).

Preterm
N=9
Term
N=17
p
Gestational age (weeks) 29.6
(26.4 – 29.9)
39.3
(38.8 – 39.7)
<0.01
Birth weight (g) 1375
(945 – 1460)
3830
(3400 – 4060)
<0.01
Whole blood platelet count (x10^9/L) 247
(178 – 264)
254
(223 – 277)
0.35
Mean platelet volume (fL) 8.3
(8.1 – 9.1)
7.6
(7.2 – 8.4)
0.04
PRP platelet count (x 10^9/L) 105
(61 – 142)
107
(93 – 179)
0.28
Lag time (mins) 3.77
(3.26 – 4.33)
4.28
(3.85 – 4.5)
0.16
Endogenous thrombin potential (nM.min) 1003
(871 – 1140)
970
(898 – 1000)
0.43
Peak thrombin (nM) 81
(60 – 102)
77
(57 – 86)
0.49
Time to peak thrombin (mins) 9.44
(8.83 – 10.17)
10.45
(9.33 – 11.74)
0.13

CAT parameters in PRP. Median values displayed (interquartile range). 
In a subset of infants (n=5 term, n=2 preterm), thrombin generation was assessed in both PPP and PRP using 1pM TF only. No difference was observed in any CAT parameters, suggesting that neonatal PPP phospholipid content (potentially from circulating extracellular vesicles) is sufficient to support thrombin generation in the absence of exogenous phospholipid.

Conclusions: These preliminary data suggest that CAT parameters in PRP are similar in preterm and term infants. Moreover, neonatal plasma phospholipid appears to support thrombin generation in the absence of exogenous phospholipid. This ongoing large prospective study aims to further characterize the platelet-dependency of neonatal thrombin generation.
 

To cite this abstract in AMA style:

Murphy C, Neary E, Kevane B, O'Reilly D, O'Loughlin J, EL-Khuffash A, Maguire P, NíAinle F, McCallion N. The Effect of Platelets on Thrombin Generation in the Premature Infant: The EVENT Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-effect-of-platelets-on-thrombin-generation-in-the-premature-infant-the-event-study/. Accessed August 16, 2022.

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