The neonatal coagulation system and the vitamin K deficiency bleeding – a mini review

Abstract

Coagulation factors do not cross the placental barrier but are synthesized independently by the conceptus. At birth, activities of the vitamin K dependent factors II, VII, IX, and X and the concentrations of the contact factors XI and XII are reduced to about 50% of normal adult values. The levels of the factors V, VIII, XIII, and fibrinogen are similar to adult values. Plasma concentrations of the naturally occurring anticoagulant proteins (antithrombin, protein C, and protein S) are significantly lower at birth than during the adult years. Plasminogen is reduced by approximately 50%. Platelet counts are within the normal range, regarding function, however, neonatal platelets seem to be hyporeactive. The von Willebrand factor contains large multimers and its concentration is increased. Properties and functions of vitamin K as well as requirement and plasma concentrations in newborns are reviewed. Regarding vitamin K deficiency bleeding (VKDB), the classical nomenclature is used: "early" (presenting within the first 24 h of life), "classical" (day 1-7 after birth), and "late" (8 days to 6 months). After the presentation of the history of vitamin K prophylaxis, vitamin K levels are described as can be expected after the administration of prophylactic doses at various routes. Subsequently, the actual schedule of vitamin K prophylaxis as recommended by the "Osterreichische Gesellschaft für Kinder- und Jugendheilkunde" is given as follows: i) the oral treatment of healthy full-term babies and orally fed preterm babies, ii) the parenteral treatment of small preterm and sick full-term babies, and iii) the treatment of mothers under medication with enzyme-inducing drugs with vitamin K during the last 15-30 days of pregnancy. The regimes of prophylactic vitamin K treatment of different countries are also given. Finally, the therapeutic use of vitamin K is addressed; the potential use of fresh-frozen plasma, prothrombin complex preparations, and recombinant factor VIIa is discussed.

Hemostatic profile in healthy premature neonates; Does birth weight affect the coagulation profile?

“…[3] Most of hemostatic indices gradually evolve during early life and reach their adult levels by 6 month. Available studies concern about coagulation system in association with GA and neonatal maturity at the time of birth.…”

“…Serum levels of anti-coagulation factors, pro-coagulants and fibrinolytic proteins vary with gestational age (GA) and consequently the birth weight. [12345678] Although developing of hemostatic system rarely accompanies by clinical symptoms in healthy term neonates, premature small for GA (SGA) neonates have higher morbidity and mortality rate due to their hemostatic disturbances predisposing them to hemorrhages or thrombotic disorders. [1237910]…”

Interpretation of clotting tests in the neonate: Table 1

“…Foetal production of coagulation proteins begins at 11 weeks’ gestation, and these cannot cross the placenta because of their size as macromolecules 6. The levels of most coagulation factors are approximately 50% the adult levels, with most reaching adult levels by 6 months of age.…”

“…The levels of most coagulation factors are approximately 50% the adult levels, with most reaching adult levels by 6 months of age. The activity of vitamin K-dependent clotting factors is approximately 50% (between 37% and 100%) of the adult values, and reduced further in preterm infants; to 30% in 24–29 weeks’ gestation (25–79%) and 20% in 19–23 weeks (11–39%) 6. The naturally occurring anticoagulants (antithrombin, protein S+protein C) are synthesised in the liver dependent on vitamin K. Plasma concentrations of these anticoagulants are significantly lower at birth than in adults (60%, 39% and 36%, respectively).…”

Change in hospital protocol regarding the use of vitamin K prophylaxis in newborns following a case of spontaneous subdural haematoma in a previously healthy 40-day-old infant

“…Industrial contaminants in breast milk have been implicated in promoting VKDB. More than half of these infants present with acute intracranial haemorrhages [6]. In addition, infants who have intestinal malabsorption defects (cholestatic jaundice, cystic fibrosis, etc.)…”