What is the recommended dose of Vitamin K for bleeding?

From the Guidelines

For active bleeding due to vitamin K deficiency or warfarin overdose, the recommended dose of vitamin K (phytonadione) is 5-10 mg given intravenously (IV) for immediate reversal, as recommended by the most recent guideline 1. This dose is supported by the European guideline on management of major bleeding and coagulopathy following trauma, which suggests that a 5-10 mg dose of vitamin K is sufficient to correct the INR without creating a prothrombotic state 1. The administration of vitamin K should be accompanied by a repletion strategy, such as the use of prothrombin complex concentrate (PCC), to achieve immediate hemostasis 1. Key points to consider when administering vitamin K include:

• The dose of vitamin K should be individualized based on the patient's INR level and clinical condition 1
• Vitamin K should be administered slowly over 20-30 minutes to avoid anaphylactoid reactions 1
• The use of PCC is associated with an increased risk of venous and arterial thrombosis during the recovery period, and thromboprophylaxis should be considered as early as possible after bleeding has been controlled 1
• After initial treatment, additional doses of vitamin K may be needed every 12-24 hours based on coagulation testing 1. It is essential to monitor the patient's INR level regularly after vitamin K administration to ensure that the coagulopathy has been adequately reversed 1.

From the FDA Drug Label

1. 2 Recommended Dosage Anticoagulant-Induced Prothrombin Deficiency in Adults The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2. 5 mg to 10 mg or up to 25 mg initially. In some instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition. If, in 12 to 48 hours after oral administration, the prothrombin time has not been shortened satisfactorily, repeat the dose Repeated large doses of phytonadione tablets are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to phytonadione may indicate a congenital coagulation defect or that the condition being treated is unresponsive to vitamin K Hypoprothrombinemia Due to Other Causes in Adults If possible, discontinuation or reduction of the dosage of drugs interfering with coagulation mechanisms (such as salicylates, antibiotics) is suggested as an alternative to administering concurrent phytonadione tablets The severity of the coagulation disorder should determine whether the immediate administration of phytonadione tablets are required in addition to discontinuation or reduction of interfering drugs. The recommended dose is 2. 5 mg to 25 mg or more (sometimes up to 50 mg). Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based upon the INR or clinical condition.

The recommended Vitamin K dose for bleeding due to anticoagulant-induced prothrombin deficiency or hypoprothrombinemia due to other causes is:

• 2.5 mg to 10 mg or up to 25 mg initially for anticoagulant-induced prothrombin deficiency
• 2.5 mg to 25 mg or more (sometimes up to 50 mg) for hypoprothrombinemia due to other causes The dose may be repeated based on prothrombin time response or clinical condition 2, 2.

From the Research

Vitamin K Dose for Bleeding

• The appropriate dose of vitamin K for bleeding associated with vitamin K antagonists is a topic of discussion in several studies 3, 4, 5.
• A study published in 2021 found that higher doses of vitamin K (10 mg) were more likely to correct International Normalized Ratio (INR) than lower doses (5 mg) in patients with major bleeding 4.
• Another study from 2011 suggests that for excessive INR elevation in the absence of bleeding, low-dose oral vitamin K (1-2.5 mg) is sufficient, while major bleeding should be managed with high-dose vitamin K (10 mg) via intravenous infusion 5.
• However, a 2020 study found that vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10 6.

Key Findings

• INR correction after intervention to manage major bleeding on vitamin K antagonists is associated with better survival 4.
• Higher doses of vitamin K (10 mg) improve INR correction more than lower doses (5 mg) in major bleeding 4.
• Vitamin K supplementation may decrease variability of INRs in patients with a history of unstable INRs 7.

Treatment Strategies

• Treatment of warfarin-associated coagulopathy with vitamin K is a cornerstone of management, with daily vitamin K supplementation emerging as an approach to regulate INRs in difficult-to-control patients 5.
• Mild warfarin-associated coagulopathy without bleeding can often be managed with warfarin withdrawal alone, while excessive INR elevation in the absence of bleeding can be managed with low-dose oral vitamin K 5.