A moderate decrease in factors II, VII, IX, and X normally occurs in all newborn infants by 48–72 hr after birth, with a gradual return to birth levels by 7–10 days of age. This transient deficiency of vitamin K–dependent factors is probably due to lack of free vitamin K from the mother and absence of the bacterial intestinal flora normally responsible for the synthesis of vitamin K. Rarely, in term infants and more frequently in premature infants, accentuation and prolongation of this deficiency between the 2nd and 7th days of life result in spontaneous and prolonged bleeding. Breast milk is a poor source of vitamin K, and hemorrhagic complications are more frequent in breast-fed than in formula-fed infants. This classic form of hemorrhagic disease of the newborn, which is responsive to and prevented by vitamin K therapy, must be distinguished from disseminated intravascular coagulopathy and from the more infrequent congenital deficiencies of one or more of the other factors that are unresponsive to vitamin K.
Early-onset life-threatening vitamin K deficiency–induced bleeding (onset from birth to 24 hr) also occurs if the mother has been treated with drugs (phenobarbital, phenytoin) that interfere with vitamin K function.
Late onset (>2 wk) is often associated with vitamin K malabsorption, as noted in neonatal hepatitis or biliary atresia.
Hemorrhagic disease of the newborn resulting from severe transient deficiencies in vitamin K–dependent factors is characterized by bleeding that tends to be gastrointestinal, nasal, subgaleal, intracranial, or postcircumcision. Prodromal or warning signs (mild bleeding) may occur before serious intracranial hemorrhage.
The prothrombin time (PT), blood coagulation time, and partial thromboplastin time are prolonged, and levels of prothrombin (II) and factors VII, IX, and X are significantly decreased. Vitamin K facilitates post-transcriptional carboxylation of factors II, VII, IX, and X. In the absence of carboxylation, such factors form PIVKA (protein induced in vitamin K absence), which is a sensitive marker for vitamin K status. Bleeding time, fibrinogen, factors V and VIII, platelets, capillary fragility, and clot retraction are normal for maturity.
Intramuscular administration of 1 mg of vitamin K at the time of birth prevents the decrease in vitamin K–dependent factors in full-term infants, but it is not uniformly effective in the prophylaxis of hemorrhagic disease of the newborn in premature infants.
The disease may be effectively treated with a slow intravenous infusion of 1–5 mg of vitamin K1, with improvement in coagulation defects and cessation of bleeding noted within a few hours. Serious bleeding, particularly in premature infants or those with liver disease, may require a transfusion of fresh frozen plasma or whole blood. The mortality rate is low in treated patients.