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Coagulation system in very premature neonates

Presented at the Neonatal Society 2015 Autumn Meeting.

Neary E1, Ainle FN2,4, Kevane B4, Egan K4, Regan I, Cotter M, McCallion N1,3

1 Department of Paediatrics, Rotunda Hospital, Ireland
2 Department of Haematology, Rotunda Hospital Ireland
3 Department of Paediatrics, RCSI, Ireland
4 School of Medicine, Conway Institute, UCD, Ireland

Background: Very premature infants are at risk of bleeding complications and are frequently given plasma because of a perception that coagulation test results are abnormal. However, “abnormal” clotting times may simply be due to physiological immaturity. We hypothesized that prospective characterization of coagulation tests alongside assessment of thrombin generation would provide information on overall haemostatic balance in this population.

Methods: In a prospective observational study, blood was drawn from cord blood of neonates (<30/40) at delivery, day 1, day 3 and week 2 from non-heparinised lines. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, procoagulant and anticoagulant factor activity were measured and tissue factor (TF)- stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. Ethical approval was obtained from Rotunda Hospital. Funding was obtained by NCRC and CFFH.

Results: Between 2013-2015, 126 infants were recruited. Median (25th-75th) gestational age and birth weight was 28 (26-29) wks and 1020 (818-1221) g. Median Day 1 values for PT, APTT and fibrinogen were 17.9 (13-18)s, 79 (49-132) s and 1.3 (1-4) g/L. PT and APTT attenuated with postnatal age (p<0.01). Endogenous thrombin potential and peak thrombin generated were comparable in preterm vs. term (n=100, p=0.08, p=0.4) and dose dependently suppressed by increasing amounts of activated protein C. Alpha 2 macroglobulin activity was estimated to be lower in preterm vs. term infants (12 (8-58) nM vs. 20 (12-25) nM, p<0.001) and increased with increasing gestational age (n=100). Factors (II, VII, IX, X) were lower in preterm vs. term infants (p=0.01, p=0.3, p=0.01, p=0.01 respectively). Protein C (p=0.004), S (p=0.07), antithrombin (p=0.01) and TFPI (P=0.1) had lower levels than controls (n=9).

Conclusion: In conclusion, in the largest prospective study of infants <30/40, we describe ranges for coagulation tests, demonstrate differences in procoagulant and anticoagulant pathways, and that thrombin generation is similar in very preterm and term infants. These findings call into question giving plasma based on laboratory parameters.

Corresponding author: nearyeb@gmail.com

Ackonowledgements: We acknowledge the staff of Rotunda Hospital and the parents and babies in this study.

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