9

• Hemorrhagic disease of the newborn

  Vitamin K deficiency that may result in clinically significant bleeding
• Objective

  • Pathogenesis
  • Clinical manifestation
  • Laboratory findings
  • Differential diagnosis
  • Treatment
• Pathogenesis


  1. Vitamin K is a group of compounds with a common naphthoquinone ring structure

  2. Deficiency of vitamin K, which is necessary for the synthesis of clotting factors II, VII, IX, and X, may result in clinically significant bleeding

  3. Phylloquinone (vitamin K1) is present in dietary sources

  4. Vitamin K2 (menaquinones) is produced by intestinal bacteria

  5. Vitamin K is a cofactor for γ-glutamyl carboxylase, an enzyme that performs post-translational carboxylation, converting glutamate residues in proteins to γ-carboxyglutamate (Gla)

  6. Gla residues, by facilitating calcium binding, are necessary for protein function
• Forms of vitamin K-deficiency bleeding (VKDB) of the newborn

  • Early VKDB (classic hemorrhagic disease of the newborn, 1-14 days of age)
  • Late VKDB (2-12 weeks of age)
  • VKDB at birth or shortly thereafter (due to maternal intake of medications)
• Early VKDB


  Secondary to low stores of vitamin K at birth due to poor transfer across placenta and inadequate intake during first few days of life, and no intestinal synthesis of vitamin K2 because newborn gut is sterile; occurs mostly in breast-fed infants due to low vitamin K content of breast milk
• Late VKDB


  Most commonly occurs at 2-12 weeks of age, although cases can occur up to 6 months after birth; almost all cases are in breast-fed infants due to low vitamin K content of breast milk; additional risk factor is occult malabsorption of vitamin K, such as in children with undiagnosed cystic fibrosis or cholestatic liver disease
• VKDB at birth or shortly thereafter

  Secondary to maternal intake of medications (warfarin, phenobarbital, phenytoin) that cross the placenta and interfere with vitamin K function
• Vitamin K-deficiency bleeding due to fat malabsorption

  May occur in children of any age
• Beyond infancy, low dietary intake by itself never causes vitamin K deficiency. However, the combination of poor intake and the use of broad-spectrum antibiotics that eliminate the intestine's vitamin K2-producing bacteria can cause vitamin K deficiency.