Introduction And Pathophysiology

  • Vitamin K deficiency bleeding (VKDB) was formerly known as hemorrhagic disease of the newborn.
  • Vitamin K acts as an essential co-factor for the synthesis and activation of coagulation factors II, VII, IX, and X, as well as proteins C and S.
  • Neonates have critically low levels of vitamin K at birth.
  • This deficiency is attributed to poor placental transfer and low vitamin K content in breast milk.
  • Additionally, the neonatal gut is sterile, lacking the normal bacterial flora that synthesize vitamin K.
  • Neonates also exhibit poor intestinal absorption of vitamin K and reduced activity levels of the vitamin K epoxide reductase enzyme,.

Classification And Clinical Presentation

  • VKDB is classified into three distinct syndromes based on the time of onset and underlying etiology.
  • Prolonged, difficult to control bleeding in a relatively well baby is a hallmark of VKDB.
Type of VKDBTime of OnsetCauses and Risk FactorsCommon Sites of BleedingSpecific Treatment Considerations
EarlyFirst 24 hours after birthMaternal exposure to medications (anticonvulsants, antibiotics, antitubercular drugs)Cephalhematoma, umbilical stump, intracranialConsider FFP for clinical bleeding; Vitamin K alone is usually not effective,.
Classic1 to 7 days after birthLack of prophylactic vitamin K at birth; poor breastfeedingGastrointestinal, mucocutaneous, post-circumcision, umbilical stump; rarely intracranialParenteral Vitamin K; consider FFP for active clinical bleeding.
Late1 to 8 weeks after birthFat malabsorption (e.g., biliary atresia, alpha-1-antitrypsin deficiency); liver and GI disordersGastrointestinal, mucocutaneous, intracranialParenteral Vitamin K; consider FFP for clinical bleeding; Recombinant factor VIIa for mild cases,.

Diagnosis

  • Coagulation profiles typically reveal a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT),.
  • The aPTT may occasionally remain normal in the early stages of the deficiency.
  • The international normalized ratio (INR) is frequently elevated to values greater than 4.
  • Proteins induced by vitamin K absence (PIVKA) are sensitive biomarkers utilized to confirm vitamin K deficiency.
  • Diagnosis is clinically confirmed by the rapid normalization of PT within 30 to 60 minutes following a vitamin K injection.

Prevention

  • Universal prophylactic administration of vitamin K is recommended immediately after birth for all neonates to prevent VKDB.
  • Neonates weighing more than 1500 g should receive a single intramuscular (IM) dose of 1 mg within 6 hours of birth,.
  • Preterm infants weighing less than 1500 g should receive a dose of 0.3 mg/kg to 0.5 mg/kg intramuscularly.
  • Intravenous (IV) vitamin K is not recommended for routine prophylaxis in preterm infants.
  • Currently available oral vitamin K preparations are not recommended for prophylaxis.

Management

Vitamin K Administration

  • Active bleeding requires prompt administration of intravenous Vitamin K1 at a dose of 1 to 2 mg,.
  • Alternatively, a dose of 250 to 300 µg/kg (up to a maximum of 10 mg) of intravenous vitamin K can be given without delay.
  • The intravenous dose must be administered slowly and should not exceed a rate of 1 mg/minute.
  • Avoid the intramuscular route in actively bleeding neonates to prevent excessive hematoma formation.
  • The subcutaneous route may be utilized if intravenous access is difficult to secure.
  • Clinical bleeding typically decreases within 20 minutes of the injection, with clotting factors rising near normal within 2 hours.

Blood Product Transfusion

  • Fresh frozen plasma (FFP) is indicated for life-threatening hemorrhage or severe intracranial bleeds,.
  • The recommended dose for FFP is 10 to 20 mL/kg to provide immediate replacement of coagulation factors,.