Approach Considerations
In general, infants with vitamin K deficiency bleeding (VKDB) do not require surgical care, but in rare cases, an infant may need neurosurgical evaluation and treatment.
Other conditions, such as those associated with short bowel syndrome and hepatobiliary disease may require surgical evaluation.
Consultations
Vitamin K deficiency bleeding usually warrants consultation with a pediatric hematologist to rule out other causes of hemorrhagic disease of the newborn. In such instances, close follow-up is needed after discharge from the hospital.
Pediatric surgery and pediatric neurosurgery consultation should be obtained when they are deemed necessary.
A pediatric hematologist may also be beneficial as a consultant.
Medical Care
Prevention of vitamin K deficiency bleeding (VKDB) with administration of intramuscular (IM) vitamin K is of primary importance in the medical care of neonates. A single dose of IM vitamin K after birth effectively prevents classic vitamin K deficiency bleeding. Conversely, oral (PO) vitamin K prophylaxis improves coagulation test results at 1-7 days, but vitamin K administered by this route has not been tested in randomized trials for its efficacy in preventing either classic or late vitamin K deficiency bleeding. [19, 20]
In their policy statements, The American Academy of Pediatrics (AAP) has endorsed the universal supplementation of vitamin K using the IM injection, because no vitamin K preparation is licensed for oral use in the United States. [31, 32, 33]
Immediately administer vitamin K subcutaneously (hold pressure on the site) for any infant in whom vitamin K deficiency bleeding is suspected or who has serious, unexplained neonatal bleeding.
Note the following:
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IM administration can result in a hematoma because of the coagulopathy.
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Intravenous (IV) administration of vitamin K has been associated with anaphylactoidlike reactions.
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Fresh frozen plasma may be considered for moderate to severe bleeding.
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Life-threatening bleeding may also be treated with prothrombin complex concentrates (PCCs). Note that despite the increasing off-label use of PCCs for neonates and infants with severe bleeding or a risk of severe bleeding, a systematic review and meta-analysis indicates there remains insufficient evidence to make a definitive recommendation for administering these products in this population. [34]
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Because the bleeding in classic vitamin K deficiency bleeding usually is not life threatening, a single dose of parenteral vitamin K is generally sufficient to stop the bleeding and return prothrombin time (PT) values to within the reference range.
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In the early 1990s, an association between parenteral vitamin K and the later occurrence of childhood cancer was reported; however, a large cohort study and a large retrospective analysis of a US database could not confirm this association. Because this association is weak at best, the AAP supports and recommends routine vitamin K prophylaxis.
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Oral vitamin K has been studied as an alternative and can improve clotting studies and vitamin K levels, but it has not been studied in large randomized controlled trials to determine if this strategy effectively prevents early and late vitamin K deficiency bleeding.
Studies from different countries have reported evidence of a rise in vitamin K prophylaxis being refused or neglected by parents. [25, 35, 36] For example, a Canadian study found that of 282,378 children born in Alberta between 2006 and 2012, neonatal prophylaxis was declined in 0.3% of cases, with the incidence of vitamin K refusal being higher in midwife-assisted births than in physician-attended deliveries. [37] In an Israeli study, in which questionnaires were answered by 217 expectant parents, 22.5% of participants were unaware of recommendations regarding neonatal vitamin K prophylaxis. [38]
A more recent US study based on 2011-2013 data in the state of Tennessee found that the parents of 3.0% of infants at hospitals refused injectable vitamin K for their newborns in 2013 (higher frequency than in years 2011 and 2012); in the same year, parents of 31% of infants at birthing centers refused vitamin K prophylaxis. [25] The most common reasons for parental refusal were a belief the injection was unnecessary (53%) and a desire for a natural birthing process (36%).
Transfer
Infants with evidence of intracranial bleeding may require transfer to a level III nursery after stabilization with subcutaneous vitamin K and other aspects of supportive care.
Discharge planning
In patients with vitamin K deficiency bleeding, follow-up for continued bleeding after vitamin K administration is indicated because other causes may be present. In addition, hematocrit levels should be obtained serially and before discharge
Ensure neurologic complications are stable or resolved before discharge.
Mild vitamin K deficiency bleeding that has been treated successfully can be monitored on an outpatient basis.
The postdischarge follow-up interval depends on the nature and severity of bleeding, the hematocrit level at discharge, and any neurologic abnormalities that could recur.
Diet and Activity
Diet
The best sources of vitamin K are green leafy vegetables, legumes, soybean, and olive oils.
Breastfed infants should receive vitamin K supplementation; if mothers refuse this prophylaxis, they should be counseled. [27] Because breast milk is not a good source of vitamin K, infants of mothers who refuse prophylaxis and who exclusively breastfeed should receive oral supplementation of vitamin K. [39]
Recommendations
Recommendations on vitamin K supplementation continue to evolve. [40] A relatively recent recommendation for oral (PO) vitamin K supplementation in term infants suggests weekly administration of 1 mg until age 12 weeks or 2 mg at birth and then repeated at age 1 week and age 4 weeks, [41] but this recommendation emphasizes a lack of information related to the dosing of oral vitamin K in preterm infants. An additional oral dose of 2 mg at age 8 weeks has also been suggested. [42]
A more recent recommendation from the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition indicates the following for vitamin K administration to healthy newborns [27] :
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One dose of 1 mg vitamin K1 given intramuscularly (IM) at birth, or
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Three doses of 2 mg vitamin K1 PO at birth, at age 4-6 days, and at age 4-6 weeks, or
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One dose of 2 mg vitamin K1 PO at birth, followed by a weekly dose of 1 mg PO for 3 months
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For infants who vomit/regurgitate the formulation within 1 hour of receiving PO vitamin K, it may be appropriate to repeat the dose.
Similarly, The French Society of Neonatology recommends the following for vitamin K prophylaxis [23] :
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For term infants: Three doses of 2 mg vitamin K1 PO at birth, at discharge from the maternity ward, and at age 1 month
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For premature infants (birth weight >1500 g): Weekly dose of 2 mg up to the term-equivalent age
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For premature infants (birth weight < 1500 g): Weekly dose of 1 mg up to 1500 g body weight; then, a weekly dose of 2 mg up to the term-equivalent age
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For infants unable to take the PO formulation: Use an IM or intravenous (IV) route with a 50% reduction in dosing
The Canadian Paediatric Society and the College of Family Physicians of Canada also recommend routine IM administration of a single dose vitamin K (0.5 mg to 1.0 mg) to all newborns. Newborns whose parents refuse IM vitamin K should receive an oral dose of 2 mg at birth, repeated at 2-4 and 6-8 weeks of age. This recommendation also notes a lack of information related to the dosing of oral vitamin K in preterm infants. [43]
Note that oral vitamin K prophylaxis may not be sufficient for infants with gastrointestinal tract–related issues, including biliary atresia and cholestasis, [27, 28] for infants too ill to receive PO vitamin K1, or for those whose mothers have taken medications that interfere with vitamin K metabolism. [27]
Activity
During acute bleeding, the infant with vitamin K deficiency bleeding should be handled with caution until the coagulation profile returns to normal after vitamin K supplementation.
Prevention
Intramuscular (IM) vitamin K prophylaxis at birth is the standard of care in the United States. [26] This prophylaxis is required even for healthy newborns who don't have bleeding risk factors. [18]
In the United States, commercial infant formulas and maternal supplements during pregnancy/lactation contain supplemental vitamin K, but these preparations are not as effective as parenteral vitamin K. [18, 27]
These measures have served to make vitamin K deficiency bleeding (VKDB) a rarity in the United States. However, parental refusal of prophylaxis and an increasing frequency of breastfeeding may cause a resurgence of vitamin K deficiency bleeding in developed countries. [26, 44]
Vitamin K1 should be given to all newborns as a single IM dose of 0.5 to 1 mg. [27, 31] Healthcare professionals should promote awareness among families of the risks of late vitamin K deficiency bleeding associated with inadequate vitamin K prophylaxis from current oral dosage regimens, particularly for newborns who are breastfed exclusively.
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Vitamin K cycle. CO<sub>2 </sub> = carbon dioxide; NAD+ = oxidized nicotinamide adenine dinucleotide; NADH = reduced nicotinamide adenine dinucleotide; O<sub>2 </sub> = oxygen; and PIVKA = protein-induced by vitamin K absence.
