Vitamin K

Overview

• Vitamin K is a group of compounds each having a common naphthoquinone ring structure
• Vitamin K1 = Phylloquinone
  
• Vitamin K2 = group called menaquinones
  
• Saturable energy dependent absorption in jejunum - requires presence of bile salts
  
• Fat Soluble
• Vit K and clotting dependent cofactors have high turnover and deficiency can occur within weeks of poor intake or malabsorption
  

Biomechanics

• Vit K is a cofactor for gamma-glutamyl carboxylase which performs posttranslational carboxylation to convert glutamate in proteins into gamma-carboxyglutamate. Glutamate (Gla) facilitates calcium binding and is necessary for protein function.
• Gla containing proteins affect bone (osteocalcin and protein S) and Vascular processes (matrix Gla protein and protein S)
• Small Vit K deficiency may have long term effects on bone strength and vascular health even when the deficiency is not significant enough to affect coagulation
  

Dietary (or other) Sources:

• Vitamin K1
• Green leafy vegetables
• Dairy products
• Soybean oil
• Fruits
• Seeds
  
• Liver
• Vitamin K2
• Byproduct of bacterial metabolism in the gut
• Not sufficient without Vitamin K1

Recommended amount

• 0.3-0.5mg/day for all ages
  

Deficiency:

• Deficiency results in:
  
• Abnormal coagulation
• Vitamin K is needed for carboxylation of glutamic acid residues on coagulation factors II, VII, IX, X and proteins C, S, and Z in the liver (Note: Protein S is also made outside of the Liver in various tissues)
  
• Protein C and S inhibits blood coagulation
  
• Bone Disease secondary to Osteocalcin's requirement for Vitamin K dependent carboxylation in bone formation
• Causes of deficiency:
• Fat malabsorption
• Inadequate intake (breastfed infants)
• Chronic antibiotic therapy (elimination of bacteria, bacteria cannot produce vitamin K2)

Clinical Manifestations

• Coagulopathy
• Prolonged PT
• Abnormal bone matrix synthesis

• There are 3 forms of Vit K deficiency bleeding (VKDB) of the newborn
• Early VKBD (formerly known as Classic hemorrhagic disease of the newborn)
• 1-14 days of age
• bleeding in the GI tract and mucosal/cutaneous tissue, umbilical stump, postcirc site
  
• Due to low stores of Vit K at birth secondary to low transfer of Vit K across the placenta and decrease/inadequate intake within the first few days of life
• Also due to no intestinal synthesis of Vit K due to sterile newborn gut
• Mostly occurs in breastfed infants -low Vit K content of breastmilk
• Late VKBD
• 2-12wks of age (can occur up to 6mo)
• Intracranial bleed (can also have GI or cutaneous bleeding first)
• Neuro Sx, Seizure, Death
  
• Almost exclusively in breastfed infants or occult malabsorption (CF, cholestatic liver disease)
• Without Vit K prophylaxis, incidence is 4-10 per 100K newborns
• Birth VKBD - due to maternal meds (warfarin, phenobarbitol, phenytoin) interfere with Vit K function in the fetus /newborn
• Note: Fat Malabsorption can cause VKDB at any age
• Cholestatic liver disease
• pancreatic disease
• intestinal disorders
• celiac
• IBD
• Short Bowel syndrome
• Prolonged diarrhea (esp in breastfed infants)
• CF most likely if patients have pancreatic insufficiency and liver disease
• Note: Low dietary intake alone never causes vitamin K deficiency AFTER INFANCY
• Poor intake and broad spectrum antibiotics which eliminate Vitamin K2 producing bacteria in the intestines CAN cause vit K deficiency after infancy
• Can be common in the ICU
• Patients on TPN without Vit K supplementation are also at risk
• Older children with Vit K deficiency may only have bruising or other bleeding
  

Dx

• Prothrombin Time (PT) is prolonged
  
• PT must be interpreted for age (newborns have a prolonged PT normally)
• PT will be normal in mild deficiency
• Vit K deficiency can be confirmed by noting improvement in a prolonged PT after parental dose of  Vit K stops active bleeding
  
• PTT is typically prolonged but may be within normal limits in early deficiency
  
• Factor VII has the shortest half-life of the coag factors and the first to be affected (however, isolated Factor VII deficiency will not affect PTT)
  
• PIVKA II Assay (proteins induced in Vitamin K absence)
  
• these are undercarboxylated proteins that would normally be carboxylated in the presence of Vit K
  
• Plasma phylloquinone
• Blood Vit K levels are not an adequate reflection of tissue stores and vary with recent dietary intake

DDx:

• Bleeding and prolonged PT can also be caused by:
• DIC (typically secondary to sepsis)
• thrombocytopenia
• low fibrinogen
• elevated D-dimers
  
• Liver Failure
• decreased production of clotting factors
• PT will not fully correct with administration of Vit K
  
• Rare hereditary deficiencies of clotting factors
• Look for deficiency of specific clotting factors
• Coumadin (Warfarin), coumarin derivatives, inhibit vit K action by preventing its reformation after it functions as a cofactor for gamma glutamyl carboxylase. Rodent poison can have the same affects.
  
• High Dose Salicylates also inhibit vit K regeneration which can cause prolonged PT and clinical bleeding

Tx:

• Infants with VKDB: 1mg of parental Vit K
• PT should decrease within  6hrs and normalize within 24hrs
• Adolescents (rapid correction): 2.5-10mg parental Vit K
• Children with Malabsorption require long term administration of high doses of PO Vit K
  
• 2.5mg 2x/wk - 5mg/day, may need to use parental Vit K if PO vit K ineffective
  
• If  bleeding is severe, infuse FFP for rapid correction of  coagulopathy

Prevention

• 1mg IM Vit K x1 soon after birth
• Review maternal medications
• Patients at high risk for malabsorption should receive supplemental Vit K and periodic PT levels
  

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3. Moore, Keith L.,, Arthur F. Dalley, II, and Keith L Moore. Clinically Oriented Anatomy. Fifth edition. Baltimore: Wolters Kluwer Health, 2009. Print.
4. Kleinman RE, Goulet O, Mieli-Vergani G, et al, eds. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. 5th ed. Hamilton, Ontario: BC Decker; 2008.
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