Presented at the Neonatal Society 2004 Autumn Meeting.
Clarke P1, Mitchell SJ2, Sundaram S3, Sharma V4, Wynn R5, Keefe D5, Roeves D6, Shearer MJ6
1 Neonatal Unit, Hope Hospital, Salford, UK
2 Neonatal Unit, St Mary’s Hospital, Manchester, UK
3 Neonatal Unit, Royal Bolton Hospital, Bolton, UK
4 Neonatal Unit, Billinge Hospital, Lancashire, UK
5 Department of Paediatric Haematology, Royal Manchester Children’s Hospital, UK
6 Centre for Haemostasis & Thrombosis, St Thomas’s Hospital, London, UK
Background: Preterm infants have immaturity of haemostasis (1). A prolonged prothrombin time (PT) is a frequent finding in the neonatal period, and vitamin K deficiency is one possible cause.
Aim: To study the vitamin K1 status of preterm infants who have a prolonged PT in the first month after delivery.
Methods: We randomised infants born at < 32 weeks’ gestation to receive vitamin K1 0.5 mg intramuscularly, 0.2 mg intramuscularly, or 0.2 mg intravenously following delivery. We routinely measured PT at 5 days postnatal age, after each infant had completed 2 weeks of full enteral feeds, and also at any time that it was clinically indicated during the study period. We considered the PT to be prolonged if it exceeded the 95% reference limits for preterm infants in the first postnatal month (PT >15.3s in the first week, and >13.6s thereafter) (1). For infants with a prolonged PT, we assessed vitamin K1 status by assay of serum vitamin K1, PIVKA-II (descarboxyprothrombin), and blood clotting factor II concentrations. We measured vitamin K1concentrations using high performance liquid chromatography, and PIVKA-II concentrations using a modified enzyme-linked immunosorbent assay. The study had prior approval from our local research ethics committees.
Results: Of 98 infants enrolled, 22 had a prolonged PT during the first month (median PT 17.1s [range 14.8 to 28.8s]). Eleven were asymptomatic and had a prolonged PT as a coincidental finding at the routine sampling times, but eleven had co-morbidity including clinical bleeding, necrotising enterocolitis, and septicaemia. Baseline characteristics (median [range]) for the 22 infants were: gestational age 27.3 weeks [22.4 to 31.4 weeks], and birthweight 816 g [466 to 1434 g]. Measures of vitamin K1 status were available for 20 infants: serum vitamin K1 concentrations ranged widely from 0.50 to 388.04 ng/mL (median 81.77 ng/mL), but all were well within or in excess of the fasting adult reference range (0.17–0.68 ng/mL); PIVKA-II was undetectable in all but one infant who had a clinically insignificant PIVKA-II concentration of 0.74 AU/mL; factor II concentrations ranged from 0.13 to 0.70 iU/mL (median 0.41 iU/mL).
Conclusion: In infants born at < 32 weeks’ gestation who receive 0.2–0.5 mg vitamin K1prophylaxis at delivery, a prolonged PT in the first month of life is not due to vitamin K deficiency.
References
1. Andrew M., Paes B., Milner R., et al. Blood 1988; 72: 1651-7.