Vitamin K and hemorrhagic disease of newborns.

First described by Charles Townsend in 1894, (1) hemorrhagic disease of newborns (HDN) is undoubtedly linked to vitamin K deficiency and can cause bleeding in infants in the first few weeks of life. It is one of the causes of acquired hemostatic disorder in early infancy. Vitamin K is a cofactor for the hepatic carboxylation of glutamic acid residues in a number of proteins, including the procoagulant factors II, VII, IX and X.

Vitamin K is transmitted poorly across the placental barrier, and at birth, vitamin K levels are often below the detection limit of 0.02 ng/mL. The clotting system of the newborn is essentially intact except for a deficiency in vitamin K dependent clotting factors. Failure to provide vitamin K at birth poses a risk for the development of hemorrhagic disease in the neonatal period. HDN is exceedingly rare in the United States because of the routine administration of prophylactic vitamin K shortly after birth.

HDN is classically defined as early or late, depending on the time of onset related to birth. The classic form of HDN usually presents on days 2 to 7 of life in healthy, breastfed, full-term infants. The common bleeding sites are gastrointestinal, cutaneous, nasal and from the site of circumcision. Late HDN presents between weeks 2 and 12 of life, and is related to conditions that interfere with the vitamin K supply. It may present with intracranial hemorrhage. This form of vitamin K deficiency is mainly due to inadequate vitamin K intake in exclusively breastfed infants. Late hemorrhagic disease of the newborn rarely occurs in formula-fed infants because of formula supplementation with vitamin K (approximately 4-100 [micro]g/L).

HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Studies from these countries showed a higher incidence of late onset vitamin K deficiency bleeding. (2) Since hemorrhagic disease of the newborn can lead to significant morbidity and mortality, it should be prevented by providing vitamin K prophylaxis to all newborns.

Does vitamin K prophylaxis prevent HDN? The answer is yes, and the data in this country support the efficacy of neonatal vitamin K prophylaxis for the prevention of HDN. The American Academy of Pediatrics recommends vitamin [K.sub.1] prophylaxis to all newborns as a single, IM dose of 0.5 to 1 mg. (3) A single IM injection of vitamin K, designed to prevent early vitamin K deficiency bleeding, may protect against late deficiency bleeding, (4) but this has not been tested in randomized trials with respect to its effect on late HDN. (5) However, one study showed a significant decline in the incidence of the late form of vitamin K deficiency bleeding. (6)

In this issue of the Southern Medical Journal, a review of two infants with intracranial hemorrhage due to hemorrhagic disease of the newborn is presented. Both were secondary to failure of vitamin K administration at birth. The infants in this report were born at home, did not receive vitamin K prophylaxis and developed intracranial hemorrhage at five weeks of age. The author concluded that late onset hemorrhagic disease of the newborn might occur when prophylactic vitamin K is not administered at birth and can have serious and even devastating consequences. This article emphasizes the association between failure of administration of vitamin K and risk of development of hemorrhagic disease of the newborn. In conclusion, HDN, although uncommon, does still occur and has the potential for severe consequences. Therefore, vitamin K prophylaxis at birth is a priority and should be provided to all newborns to prevent HDN and its associated complications, including intracranial hemorrhage.

References

1. Townsend CW. The Hemorrhagic disease of the newborn. Arch Pediatr 1894;11:559.

2. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics 2003;112:191-192.

3. Danielsson N. Intracranial haemorrhage due to late onset vitamin K deficiency bleeding in Hanoi province, Vietnam. Arch Dis Child Fetal Neonatal Ed 2004;89:F546-550.

4. Hey E. Vitamin K-what, why, and when. Arch Dis Child Fetal Neonatal Ed 2003;88:F80-83.

5. Puckett RM, Offringa M. Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev 2000;:CD002776.

6. Sutor AH, Dagres N, Niederhoff H. Late form of vitamin K deficiency bleeding in Germany. Klin Padiatr 1995;207:89-97.

Muhammad Waseem, MD

From the Department of Emergency Medicine, Lincoln Hospital, Weill Medical College of Cornell University, Bronx, NY.

Reprint requests to Muhammad Waseem, MD, Weill Medical College of Cornell University, Department of Emergency Medicine, Lincoln Hospital, 234 E. 149th Street, Bronx, NY 10451. Email: [e-mail]