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To characterize standard laboratory coagulation parameters and plasma thrombin generation in very preterm infants and to investigate their relationship to clinical outcomes

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posted on 22.11.2019 by Elaine Neary

Very premature infants are at risk of bleeding and frequently given plasma because of perception that coagulation tests are abnormal, which may simply be due to immaturity. We hypothesized that characterization of coagulation tests alongside assessment of thrombin generation would provide information on preterm haemostasis.

In a prospective observational study, cord and peripheral blood was drawn from neonates <30/40 and on day 1, 3 and fortnightly until 30/40 corrected gestational age (GA). Exclusion criteria included antenatal intraventricular haemorrhage and parental bleeding disorder. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, procoagulant and anticoagulant factor activity were measured and thrombin generation was characterized. Cord blood of term neonates provided control plasma.

Between 2013 - 2015, 137 infants <30/40 were recruited. Median (range) GA and birth weight were 27.9 (23.7-29.9) weeks and 1020 (510-1730) g respectively. Median (5th-95th percentile) Day 1 PT, APTT, and fibrinogen were 17.9 (12.8-27.7) s, 79.1 (48.8-134.3) s and 1.3 (0.7-3.9) g/L respectively (n=127). PT and APTT from preterm cord blood (n=42) were prolonged vs. controls (n=27, p

Preterm cord blood peak thrombin and endogenous thrombin potential were similar to controls (132 (40.6) nM vs. 136.7(35) nM; p=0.66 and 1168(289) nM*min vs. 1303 (190) nM*min; p=0.11) respectively (n=27). 20 Mean activity of procoagulant factors II, VII, IX and X (0.31 (0.18-0.5) IU/ml vs. 0.44 (0.35-0.6) IU/ml, p=0.003; 0.33 (0.09-0.57) IU/ml vs. 0.42 (0.31-0.59) IU/ml, p=0.29; 0.16 (0.09-0.5) IU/ml vs. 0.29 (0.19-0.37) IU/ml, p=0.004 and 0.28 (0.13-0.52) IU/ml vs. 0.44 (0.32-0.58) IU/ml, p=0.02) respectively, n=12 and anticoagulant factors Protein C (0.11U/ml (0.06-0.24) IU/ml vs. 0.27 (0.18-0.39) IU/ml; p=0.002), free protein S (0.38 (0.28-0.55) IU/ml vs. 0.47 (0.36-0.59) IU/ml; p=0.02), antithrombin (0.22 (0.06-0.36) IU/ml vs. 0.53 (0.38-0.69) IU/ml; p

In conclusion, we describe ranges for coagulation tests, demonstrate differences in both procoagulant and anticoagulant pathways, and show that thrombin generation is similar in very preterm and term infants.

Funding

This work was funded by the Maime O’Connell Research Fellowship Award, National Children’s Research Centre (Grant No. D/13/3) and Children’s Fund for Health (Grant No. PAC 12-6) and Health Research Board Cochrane Fellowship Award (Grant No. CTF-2014-879)

History

First Supervisor

Professor Naomi McCallion

Second Supervisor

Dr Fionnuala Ni Ainle

Third Supervisor

Dr Melanie Cottor

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2016.

Published Citation

Neary E. To characterize standard laboratory coagulation parameters and plasma thrombin generation in very preterm infants and to investigate their relationship to clinical outcomes [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2016.

Degree Name

Doctor of Philosophy (PhD)

Date of award

30/11/2016

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