Vitamin K injection delivers phytomenadione (vitamin K1) intravenously or intramuscularly to rapidly correct vitamin K deficiency or reverse warfarin-induced anticoagulation. Unlike oral formulations, injectable vitamin K provides immediate access to the bloodstream, enabling faster therapeutic action in clinically urgent situations such as major bleeding or emergency surgery. In the UK, vitamin K injection is primarily used to reverse warfarin over-anticoagulation—often alongside prothrombin complex concentrate (PCC)—and for neonatal prophylaxis against vitamin K deficiency bleeding (VKDB), as recommended by NICE guidance. This article explores the mechanism, clinical indications, dosing protocols, safety considerations, and monitoring requirements for vitamin K injection in UK clinical practice.

What Is Vitamin K Injection and How Does It Work?

Vitamin K injection refers to injectable formulations of phytomenadione (vitamin K1), administered intravenously or intramuscularly to rapidly correct vitamin K deficiency or reverse anticoagulation. Unlike oral supplements, injectable preparations deliver the vitamin directly into the bloodstream, enabling faster therapeutic action when immediate correction is clinically necessary.

Vitamin K functions as an essential cofactor for the hepatic synthesis of clotting factors II (prothrombin), VII, IX, and X, as well as anticoagulant proteins C and S. The vitamin undergoes a cyclic process in the liver, where it is reduced to its active hydroquinone form by the enzyme vitamin K epoxide reductase complex subunit 1 (VKORC1). This active form then serves as a cofactor for gamma-glutamyl carboxylase, which carboxylates glutamic acid residues on clotting factor precursors, rendering them biologically active. Without adequate vitamin K, these clotting factors remain undercarboxylated and functionally impaired, leading to coagulopathy.

Warfarin and other vitamin K antagonists (VKAs) inhibit VKORC1, thereby depleting active vitamin K and reducing clotting factor synthesis. Administration of vitamin K injection provides sufficient substrate to restore coagulation through alternative reductase pathways. The onset of action varies by route: intravenous administration typically begins to correct the international normalised ratio (INR) within 4–6 hours, with maximal effect at 12–24 hours, whilst intramuscular injection acts more slowly and less predictably. This pharmacological profile makes vitamin K injection valuable in managing bleeding or urgent surgical situations where reversal of anticoagulation is required, though immediate reversal requires additional measures such as prothrombin complex concentrate (PCC).

Clinical Uses of Vitamin K in Injectable Form

The primary indication for vitamin K injection is the reversal of warfarin-induced over-anticoagulation, particularly when the INR is significantly elevated or the patient presents with major bleeding or requires urgent surgery. According to NICE Clinical Knowledge Summary on oral anticoagulation and British Society for Haematology (BSH) guidance, vitamin K should be administered alongside prothrombin complex concentrate (PCC) in cases of life-threatening haemorrhage associated with warfarin therapy. The combination provides both immediate clotting factor replacement (via PCC) and sustained correction through endogenous factor synthesis (via vitamin K).

Vitamin K injection is also indicated for treating vitamin K deficiency bleeding (VKDB) in neonates, a potentially serious condition affecting newborns with inadequate vitamin K stores. In the UK, all newborns are offered prophylactic vitamin K at birth, as recommended by NICE guideline NG194, typically via intramuscular injection (1 mg for term infants), to prevent early, classical, and late VKDB. When bleeding does occur, therapeutic doses of vitamin K are administered promptly according to age-appropriate dosing and local neonatal protocols, alongside supportive measures.

Other clinical scenarios requiring vitamin K injection include:

• Malabsorption syndromes: Conditions such as coeliac disease, cystic fibrosis, or biliary obstruction impair fat-soluble vitamin absorption, potentially causing vitamin K deficiency and coagulopathy

• Antibiotic-associated deficiency: Prolonged broad-spectrum antibiotic therapy may disrupt gut flora responsible for vitamin K2 synthesis

• Hepatic dysfunction: Whilst vitamin K cannot correct coagulopathy caused by severe liver failure (where synthetic capacity is lost), it may help in cases where deficiency coexists with liver disease

• Nutritional deficiency: Rare in developed countries but may occur with severe dietary restriction or total parenteral nutrition without adequate supplementation

Importantly, vitamin K injection does not reverse the anticoagulant effects of direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, or dabigatran. For these agents, specific reversal strategies include idarucizumab (for dabigatran) or andexanet alfa (for factor Xa inhibitors) where available.

The decision to use intravenous versus intramuscular administration depends on clinical urgency, bleeding risk, and patient factors. Intravenous routes are reserved for situations requiring rapid correction, whilst intramuscular administration is generally avoided in anticoagulated adults due to haematoma risk but is appropriate for neonatal prophylaxis.

Dosage and Administration of Vitamin K Injection

Dosing of vitamin K injection varies considerably depending on the clinical indication, severity of coagulopathy, and urgency of correction. For warfarin reversal, NICE and British Society for Haematology guidelines recommend a stratified approach:

• Major or life-threatening bleeding: Administer 5–10 mg intravenous vitamin K alongside PCC, regardless of INR; vitamin K should be given by slow intravenous injection or infusion over at least 10 minutes to minimise adverse reactions

• INR >8.0 without bleeding: Give 1–5 mg oral or intravenous vitamin K; lower doses (1–2 mg) are preferred to avoid prolonged warfarin resistance

• INR 5.0–8.0 without bleeding: Withhold warfarin and consider 1–2 mg oral vitamin K if bleeding risk is high

For neonatal prophylaxis, the standard UK regimen per NICE NG194 is 1 mg intramuscularly at birth for term infants, or alternatively, three oral doses (2 mg at birth, 1 week, and 4–6 weeks) for parents declining injection. Preterm or low birthweight infants may require adjusted dosing according to local protocols and the Summary of Product Characteristics. Therapeutic treatment of VKDB requires specialist paediatric input with age-appropriate dosing; neonates typically receive 1 mg administered intravenously or intramuscularly, with further doses guided by coagulation response.

In malabsorption or nutritional deficiency, dosing should be individualised based on specialist advice and BNF recommendations, with the route determined by the underlying condition. Patients with fat malabsorption often require parenteral administration for reliable absorption.

Administration technique is crucial for safety. Intravenous vitamin K may be given as a slow IV injection or diluted in glucose 5% or sodium chloride 0.9% and infused slowly (maximum rate 1 mg/minute) to reduce the risk of anaphylactoid reactions. Rapid IV injection should be avoided due to the risk of hypersensitivity reactions. Intramuscular injection should be avoided in patients with active bleeding or severe coagulopathy due to the risk of haematoma formation, except in neonatal prophylaxis. The subcutaneous route is not recommended due to erratic absorption. The MHRA advises that intravenous administration should be undertaken with appropriate monitoring and resuscitation facilities available.

Side Effects and Safety Considerations

Whilst vitamin K injection is generally well-tolerated, several important adverse effects and safety considerations warrant attention. The most serious risk associated with intravenous administration is hypersensitivity reactions, which can manifest as flushing, dyspnoea, chest tightness, hypotension, and in rare cases, cardiovascular collapse. These reactions are thought to relate to the formulation excipients rather than vitamin K itself and are less common with current mixed micelle formulations. The MHRA emphasises that intravenous vitamin K should be administered slowly with close monitoring during and after infusion.

Other recognised adverse effects include:

• Injection site reactions: Pain, swelling, or haematoma formation at intramuscular injection sites, particularly in patients with coagulopathy

• Hyperbilirubinaemia: Rarely reported with older formulations; current evidence suggests standard prophylactic doses of phytomenadione do not increase jaundice risk in neonates

• Warfarin resistance: Excessive vitamin K dosing can render patients resistant to warfarin re-anticoagulation for several days or weeks, complicating management in those requiring ongoing anticoagulation

Contraindications are limited but important. Vitamin K should not be administered to patients with known hypersensitivity to phytomenadione or formulation components. It is not effective in reversing the effects of direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, or dabigatran, as these agents do not work via vitamin K-dependent pathways. For DOAC reversal, specific agents (idarucizumab for dabigatran; andexanet alfa for factor Xa inhibitors) should be considered according to NICE guidance and local protocols.

Patients receiving vitamin K for warfarin reversal should be counselled that the effect is sustained, and careful consideration must be given to the timing of warfarin recommencement if ongoing anticoagulation is indicated. Those with mechanical heart valves or high thromboembolic risk require particularly careful management, often involving bridging anticoagulation strategies.

Patients should be advised to report any suspected side effects to their healthcare professional or directly to the MHRA Yellow Card scheme. Any patient experiencing symptoms suggestive of allergic reaction during or after vitamin K administration should seek immediate medical attention.

Monitoring and Follow-Up After Vitamin K Treatment

Appropriate monitoring following vitamin K injection is essential to ensure therapeutic efficacy, guide further management, and detect complications. The cornerstone of monitoring is serial measurement of the INR or prothrombin time (PT), which reflects the functional status of vitamin K-dependent clotting factors.

For patients receiving vitamin K to reverse warfarin over-anticoagulation, INR should be checked:

• 30–60 minutes post-PCC administration (if given) to confirm immediate correction

• 4–6 hours post-vitamin K administration to assess initial response, particularly in cases of major bleeding where additional interventions may be needed

• 12–24 hours post-administration to confirm adequate correction and guide further vitamin K dosing

• Daily thereafter until INR stabilises within the target range, especially if warfarin is to be restarted

In cases of major bleeding, ongoing clinical assessment is paramount. Patients require monitoring of haemodynamic parameters, haemoglobin levels, and transfusion requirements. Imaging may be necessary to identify bleeding sources or assess haematoma expansion. Multidisciplinary involvement, including haematology and surgical teams, is often appropriate.

For neonates treated for VKDB, monitoring includes coagulation studies (PT, activated partial thromboplastin time), full blood count, and clinical assessment for ongoing or recurrent bleeding. Neuroimaging may be indicated if intracranial haemorrhage is suspected. Parents should be educated about signs of bleeding that require urgent medical attention, including severe headache, vomiting, unusual drowsiness, or seizures.

Patients with underlying malabsorption or chronic deficiency require longer-term follow-up to ensure adequate vitamin K status. This may involve periodic coagulation screening and assessment of the underlying condition. Nutritional review and optimisation of fat-soluble vitamin supplementation are important components of ongoing care.

Warfarin recommencement after vitamin K administration requires careful planning. The timing depends on the indication for anticoagulation, bleeding risk, and vitamin K dose administered. Patients given large doses (>5 mg) may exhibit warfarin resistance for up to two weeks. Bridging with low-molecular-weight heparin may be considered in high-risk patients. Close liaison with local anticoagulation services ensures safe and effective management. Patients should be advised to report any signs of bleeding (black stools, heavy uncontrolled bleeding) or thrombosis (limb swelling, chest pain, breathlessness) and attend scheduled monitoring appointments. Documentation of vitamin K administration, including dose, route, and indication, is essential for continuity of care and future clinical decision-making.

Frequently Asked Questions