What's in a name? The pharmacy of vitamin K
Year: 2015
Type: article
Abstract: We would like to highlight current practice relating to the pharmacy of vitamin K and its inadvertent clinical misuse in reversal of anticoagulation due to confusion surrounding the potency of the two forms prescribed. Currently, both phytomenadione (vitamin K1) and menadiol sodium phosphate (vitamin K3) are available from pharmacies and may be prescribed interchangeably as 'vitamin K'. This is an issue we have seen in practice. Recently, a patient at the Royal Free Hospital London, requiring reversal of anticoagulation by warfarin was inadvertently prescribed oral vitamin K3 (10 mg/day). Initially the patient failed to respond for three days until the treatment was switched to oral vitamin K1 (10 mg/day), which successfully reversed the anticoagulation within 24 h. The patient had no clinical history of lipid malabsorption, which is the main indication for vitamin K3. Vitamin K functions as a cofactor for a microsomal enzyme, γ-carboxyglutamyl carboxylase (GGCX), which catalyses the post-translational modification, essential for the biological activity of various proteins including coagulation factors II, VII, IX and X (Sadler, 2004). The naturally occurring K vitamins comprise the plant form, vitamin K1 and the multiple forms of menaquinones (vitamin K2), predominately of bacterial origin (Shearer & Newman, 2014). Menaquinone-4 (MK-4) is atypical, as it can be synthesised in vivo by the prenylation of the metabolic intermediate, vitamin K3, which is generated by side chain cleavage of vitamin K1 (Nakagawa et al, 2010; Shearer & Newman, 2014). In the UK, the most widespread medical use of this vitamin is for the prophylaxis of vitamin K deficiency bleeding of the newborn (Shearer, 2009). Whereas this use of vitamin K is well regulated and limited only to use of vitamin K1 (Shearer, 2009), both vitamin K1 and vitamin K3 are available for use in other conditions, including vitamin K deficiency and reversal of anticoagulation by vitamin K antagonists. In vitro studies demonstrate that vitamin K1 has cofactor activity for GGCX, but that vitamin K3 does not (Buitenhuis et al, 1990). Activity possessed by vitamin K3 in vivo is only conferred post-conversion to MK-4. Studies of subjects anticoagulated with vitamin K antagonists have confirmed that vitamin K1 administration results in rapid correction of coagulation, whereas vitamin K3 does not show any significant benefit compared to subjects not given vitamin K (Bannon et al, 1953; Gamble et al, 1955). Some recently published recommendations and reviews refer only to 'vitamin K' when discussing reversal of anticoagulation, without specifying the form that should be administered (Garcia et al, 2010; Keeling et al, 2011). In order to investigate current pharmacy practice, we undertook a small survey. We contacted eight London hospital pharmacies and asked, 'If you received a prescription for 'oral vitamin K' in an adult, what would you dispense?' All eight pharmacies confirmed that they would primarily dispense vitamin K1, but that they would look at the clinical scenario and vitamin K3 may be dispensed in cases of lipid malabsorption. A lack of precise regulatory guidance for vitamin K when used as a pharmaceutical and a propensity for clinicians to use the hypernym 'vitamin K', which is to some extent perpetuated in some guidelines and other literature, leaves room for confusion. Generally, misuse of vitamin K3 seems to be mitigated by pharmacists who have good awareness of the issue (backed up by appropriate guidance from the British National Formulary) but occasionally patients may receive a form of the vitamin that is inappropriate for their care. Given the lack of potency of vitamin K3, we suggest that vitamin K1 should be always specified when requesting a prescription for the reversal of anticoagulation by vitamin K antagonists. Vitamin K3 is indicated for the prophylaxis and treatment of vitamin K deficiency in malabsorption syndromes where patients lack bile salts or the transport lipoproteins necessary for hepatic uptake of the fat-soluble form vitamin K1 (Joint Formulary Committee, 2014). If a patient requires anticoagulant reversal and they have impaired absorption of vitamin K1 we recommend intravenous vitamin K1 should be administered. The manuscript was prepared and written by David Card. The other co-authors identified supporting evidence and edited the manuscript. There are no actual or potential conflicts of interest capable of influencing judgement on the part of any author.
Source: British Journal of Haematology
DOI: 10.1111/bjh.13828
Language: English
Topic: Vitamin K Research Studies
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2098379663