Vitamin K deficiency

Summary

Vitamin K deficiency is a common cause of an acquired bleeding disorder. Vitamin K is a fat-soluble vitamin needed to activate clotting factors II, VII, IX, X and proteins C and S. When it is missing, the body cannot make functional clotting factors → bleeding tendency.

It happens mostly in:

• Newborns (low stores, sterile gut, low vitamin K in breast milk).
• Adults with malabsorption (cholestasis, celiac, cystic fibrosis), prolonged antibiotic use, poor diet, or warfarin therapy.

The classic lab picture is ↑ PT/INR first, then ↑ PTT, with normal platelets and normal fibrinogen. Treatment is simple and effective: vitamin K replacement, plus FFP if active bleeding.

Background – Vitamin K basics

Vitamin K is a fat-soluble vitamin obtained from two sources:

• K1 (phylloquinone) – from green leafy vegetables (spinach, kale, broccoli).
• K2 (menaquinone) – synthesized by colonic bacteria.

Function: Vitamin K is a cofactor for γ-glutamyl carboxylase in the liver. This enzyme adds a carboxyl group (-COOH) to glutamate residues on certain clotting proteins, allowing them to bind Ca²⁺ and phospholipid surfaces and become active.

Vitamin K–dependent factors:

• Procoagulants: II, VII, IX, X
• Anticoagulants: Protein C, Protein S

Warfarin inhibits vitamin K epoxide reductase (VKOR) → blocks regeneration of active vitamin K → same end result as deficiency.

Etiology

Vitamin K deficiency develops when intake, absorption, or production is disrupted.

1. Newborns (high risk)

• Low placental transfer of vitamin K.
• Sterile gut → no bacterial synthesis.
• Breast milk is low in vitamin K (formula is fortified).
• → Causes Vitamin K Deficiency Bleeding of the Newborn (VKDB), formerly called hemorrhagic disease of the newborn.

2. Malabsorption of fat

• Cholestasis / obstructive jaundice (no bile salts → no fat absorption).
• Celiac disease, cystic fibrosis, chronic pancreatitis, short bowel syndrome.
• Any cause of steatorrhea.

3. Drugs

• Warfarin (inhibits VKOR).
• Broad-spectrum antibiotics – kill colonic flora that produce K2.
• Anticonvulsants (phenytoin), isoniazid, rifampin.

4. Decreased intake

• Severe malnutrition, prolonged TPN without supplementation, alcoholism.

5. Liver disease

• Liver cannot use vitamin K even if available → similar bleeding picture but vitamin K replacement does not correct PT.

Pathophysiology

Without vitamin K, the liver still makes factors II, VII, IX, X — but they are non-functional (called PIVKA: Proteins Induced by Vitamin K Absence). They cannot bind Ca²⁺ → cannot localize to platelet phospholipid surfaces → coagulation cascade fails.

Factor VII has the shortest half-life (~4–6 hours) → its activity drops first → PT/INR prolongs first (extrinsic pathway). Later, factors II, IX, X fall → PTT prolongs too.

Platelets and fibrinogen are not vitamin K dependent → counts and fibrinogen stay normal. This is what separates vitamin K deficiency from DIC.

Clinical features

Bleeding is the only symptom; pattern is mixed (both mucocutaneous and deep) because both intrinsic and extrinsic pathways are affected.

In adults

• Easy bruising, ecchymoses.
• Mucosal bleeding: epistaxis, gum bleeding, hematuria.
• GI bleeding: melena, hematemesis.
• Prolonged bleeding after minor cuts, surgery, or venipuncture.
• Severe cases: intracranial or retroperitoneal hemorrhage.

In newborns (VKDB)

Three patterns based on timing:

• Early VKDB (< 24 h): mother on warfarin / phenytoin / rifampin. Cephalhematoma, intracranial bleed.
• Classic VKDB (days 2–7): umbilical stump bleeding, GI bleeding (hematemesis, melena), circumcision bleeding, bruising. Most common form.
• Late VKDB (2 weeks – 6 months): exclusively breastfed infant who missed the IM vitamin K dose; presents with intracranial hemorrhage — high mortality.

Diagnosis

Diagnosis is mainly clinical + coagulation labs; a confirmatory step is the response to vitamin K replacement.

Lab pattern

• PT / INR → markedly prolonged (first abnormality).
• aPTT → prolonged (later, when factors IX and X drop).
• Platelets → normal.
• Fibrinogen, D-dimer → normal (distinguishes from DIC).
• Bleeding time → normal.
• Mixing study → corrects (factor deficiency, not inhibitor).

Confirmatory test

PT corrects within 24 hours after vitamin K administration → confirms deficiency and rules out liver failure.

Vitamin K deficiency vs liver disease vs DIC — quick differentiation:

Differential diagnosis – lab comparison

Use the labs to localize the cause quickly:

Key clue:

• Factor VIII normal in vitamin K deficiency but low in DIC (factor VIII is NOT vitamin K dependent — it's made by liver endothelial cells too, and acts as an acute-phase reactant in liver disease).
• Normal fibrinogen + normal platelets → rule out DIC.
• PT corrects with vitamin K → rule out liver failure.

Management

1. Vitamin K replacement (phytonadione)

• Oral – mild deficiency, no active bleeding, intact absorption.
• Subcutaneous / IV – when oral is not possible or absorption is impaired.
  • IV must be given slowly — rapid infusion can cause anaphylactoid reactions.
• IM is avoided in coagulopathic patients (risk of hematoma).
• PT begins correcting within 6–12 hours; full correction by 24 hours.

2. Active or severe bleeding

• Fresh Frozen Plasma (FFP) – immediate replacement of all clotting factors.
• Prothrombin Complex Concentrate (PCC, 4-factor) – preferred when rapid reversal is needed (e.g., warfarin-related life-threatening bleed, intracranial hemorrhage). Faster and smaller volume than FFP.
• Give vitamin K together with FFP/PCC so the effect lasts after the transfused factors decay.

3. Warfarin reversal (quick guide)

• INR 4.5–10, no bleeding → hold warfarin ± low-dose oral vitamin K.
• INR > 10, no bleeding → hold warfarin + oral vitamin K (2.5–5 mg).
• Any serious bleeding → IV vitamin K (5–10 mg) + 4-factor PCC (or FFP if PCC unavailable).

4. Treat the underlying cause

• Treat malabsorption (bile salts, gluten-free diet, pancreatic enzymes).
• Stop offending drug if possible.
• Long-term: low-dose oral vitamin K supplementation.

Prevention in newborns

Universal prophylaxis is the standard of care:

• Single IM dose of vitamin K1 (phytonadione) 0.5–1 mg given to every newborn within 1 hour of birth.
• This single dose prevents all three forms of VKDB (early, classic, late).
• Oral vitamin K is less reliable (requires multiple doses, still risk of late VKDB).

Mnemonics