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PE12.5-6 | Vitamin K — SDL Guide (Part 2)

Vitamin K Deficiency Bleeding (VKDB): Classification and Clinical Features

VKDB — previously called Haemorrhagic Disease of the Newborn (HDN) — is classified into three clinical forms based on the timing of presentation, which reflects different causative mechanisms and identifies different at-risk infant populations. This classification is clinically important because the form dictates both the urgency and the preventive strategy. The shift in nomenclature from HDN to VKDB reflects a better mechanistic understanding — the condition is not restricted to the neonatal period (late VKDB occurs up to 6 months), and the term HDN was sometimes confused with other haemorrhagic disorders of neonates. Understanding the timing of each form allows the clinician to immediately generate the correct hypothesis when a bleeding infant presents: a birth-day bleed prompts a question about maternal drug exposure; a day-3 bleed raises the question of missed prophylaxis; and a bleed at 3 weeks of age in a breastfed infant without prophylaxis is late VKDB until proven otherwise — a medical emergency.

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Classification of VKDB:

EARLY VKDB (within the first 24 hours of life):
• Timing: onset within 24 hours of birth
• Cause: maternal ingestion of drugs that cross the placenta and interfere with Vitamin K metabolism — anticonvulsants (phenobarbitone, phenytoin), anti-tuberculosis drugs (rifampicin, isoniazid), anticoagulants (warfarin), cephalosporins (broad-spectrum, inhibit K2 synthesis)
• Clinical features: bleeding from umbilicus, gastrointestinal tract, cephalhaematoma, subgaleal haemorrhage, intracranial haemorrhage (rare)
• Prevention: Vitamin K given to the mother during the last month of pregnancy AND to the neonate at birth

CLASSIC VKDB (day 2–7 of life):
• Timing: days 2–7 (peak days 2–4)
• Cause: inadequate Vitamin K intake (exclusively breastfed, low breast milk K content) combined with no prophylaxis at birth; normal physiological nadir of Vitamin K-dependent factors
• At-risk infant: exclusively breastfed, no IM Vitamin K at birth
• Clinical features: umbilical cord oozing, bleeding from circumcision site, gastrointestinal bleeding (malaena, haematemesis), ecchymoses, bleeding from injection sites
• Prevention: routine IM Vitamin K 1 mg at birth

LATE VKDB (2 weeks to 6 months of age):
• Timing: 2 weeks to 6 months (peak 3–8 weeks)
• Cause: exclusive breastfeeding without prophylaxis, OR fat malabsorption (cholestatic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, biliary atresia)
• At-risk infant: exclusively breastfed without birth prophylaxis; infants with undiagnosed cholestasis
• Clinical features: most dangerous form — intracranial haemorrhage (ICH) in 30–50% of cases; subdural, subarachnoid, or intracerebral haemorrhage causing sudden deterioration, vomiting, tense fontanelle, seizures, apnoea; other bleeding sites (skin, gastrointestinal)
• Prognosis: 20% mortality; 30–50% permanent neurological sequelae (hemiplegia, developmental delay, visual impairment)
• Prevention: routine IM Vitamin K at birth is the only reliable prevention; cholestasis identified early requires ongoing fat-soluble vitamin supplementation

Diagnosis, Management and Prevention of VKDB

The diagnosis of VKDB combines the clinical context (breastfed newborn, no birth prophylaxis, relevant drug exposure, underlying malabsorption) with a characteristic coagulation profile. Prompt recognition and immediate treatment are essential to prevent catastrophic bleeding, particularly intracranial haemorrhage in late VKDB. The key diagnostic principle is that VKDB is a disorder of secondary haemostasis — coagulation factor deficiency — with entirely intact primary haemostasis (platelets and vessel-wall response). This distinction immediately separates VKDB from immune thrombocytopenia (ITP), neonatal alloimmune thrombocytopenia, and disseminated intravascular coagulation (DIC, which typically has both low platelets AND prolonged PT/aPTT). The combination of prolonged PT AND prolonged aPTT with normal platelet count and normal bleeding time is pathognomonic of a factor-deficiency coagulopathy, and in the appropriate clinical context is sufficient to initiate Vitamin K treatment without delay.

Diagnostic investigations:
• Prothrombin time (PT): markedly prolonged — this is the most sensitive test for VKDB because Factor VII (extrinsic pathway, shortest half-life) is depleted early
• Activated partial thromboplastin time (aPTT): also prolonged (Factors IX, X, II depleted)
• Platelet count: NORMAL — distinguishes from thrombocytopenia
• Bleeding time: NORMAL — primary haemostasis intact
• PIVKA-II (des-gamma-carboxyprothrombin): elevated — most specific marker of subclinical Vitamin K deficiency; not routinely available
• Response to Vitamin K (the 'Koller test' equivalent): normalisation of PT within 4–6 hours of Vitamin K administration confirms VKDB

Management:

Situation	Vitamin K	FFP	Other
Suspected VKDB (active bleeding)	1 mg IV immediately (or IM if IV unavailable)	10–15 mL/kg IV (provides immediate factor replacement)	Identify source of bleeding; neuroimaging if ICH suspected
Suspected VKDB (no active bleeding)	1 mg IM	Not required	Monitor PT at 4–6 hours
VKDB secondary to malabsorption	1 mg IM/IV + address underlying cause	As needed	Consider ongoing supplementation

Key management point: Vitamin K takes 4–6 hours to correct PT (liver needs time to synthesise new carboxylated factors after Vitamin K is administered). For severe, life-threatening bleeding (intracranial haemorrhage), FFP provides immediate coagulation factors and should be given concurrently with Vitamin K.

Prevention — National Vitamin K Prophylaxis Protocol (IAP/NIS):
This is the most important programmatic intervention:
• All newborns (term and preterm) should receive Vitamin K prophylaxis at birth, regardless of mode of delivery or feeding intention
• Dose: 1 mg IM for newborns ≥2.5 kg (or ≥35 weeks gestation)
• Dose: 0.5 mg IM for newborns <2.5 kg (or <35 weeks gestation)
• Route: intramuscular is preferred over oral because IM provides reliable, single-dose long-term protection; oral regimens require multiple doses (3–4 doses over weeks) and have lower bioavailability
• Timing: within the first few hours after birth

Newborn VKDB: Diagnosis, Emergency Treatment, and Prevention

Self-Assessment

Returning to the opening case: the 3-week-old exclusively breastfed infant born at home with no postnatal medications has late VKDB with intracranial haemorrhage. The coagulation profile (PT 45 s, aPTT 98 s, platelets 280 × 10⁹/L) is diagnostic — prolonged PT and aPTT with entirely normal platelet count and bleeding time points exclusively to Vitamin K-dependent factor deficiency. The precipitating factors are the complete picture: home birth, exclusive breastfeeding (low breast milk K1 content ~1-3 mcg/L), no prophylaxis at birth, age 3 weeks (the classic late-VKDB window of 2 weeks to 6 months). The single injection of 1 mg Vitamin K IM at birth — a five-second intervention costing almost nothing — would have completely prevented this intracranial haemorrhage and its lifelong neurological consequences.

Key examination recall points:
• VKDB early: within 24 hours; due to maternal drugs (phenytoin, rifampicin, warfarin)
• VKDB classic: day 2–7; breastfed, no prophylaxis
• VKDB late: 2 weeks to 6 months; breastfed/malabsorption; ICH in 30–50%
• Coagulation profile: prolonged PT AND aPTT, normal platelets and bleeding time
• PIVKAs: biologically inactive coagulation factors produced without Vitamin K
• Treatment: IV Vitamin K 1 mg + FFP 10–15 mL/kg for active/severe bleeding
• Prophylaxis: 1 mg IM at birth for ≥2.5 kg; 0.5 mg IM for <2.5 kg
• Breast milk Vitamin K: ~1–3 mcg/L (very low — cannot substitute for prophylaxis)
• Warfarin inhibits Vitamin K epoxide reductase (VKOR) — same pathway, applied pharmacology

Coagulation Profiles: VKDB, Thrombocytopenia, and Haemophilia