Vitamin K1 (phytonadione) is the commercial preparation of the natural form of vitamin K (phylloquinone) that is indicated for the reversal of elevated prothrombin times (PTs) and international normalized ratios (INRs) in patients with xenobiotic-induced vitamin K deficiency. Acquired vitamin K deficiency is typically induced following the therapeutic administration of warfarin, or following the overdose of warfarin or the long-acting anticoagulant rodenticides (LAARs), such as brodifacoum. The optimal dosage regimen of vitamin K1 to treat patients who develop an elevated INR while receiving warfarin has been reviewed and a revised guideline regarding the dose and route of administration published.1,7 Oral administration of vitamin K1 is used safely and successfully. Because intravenous administration of vitamin K1 may be associated with anaphylactoid reactions, it should be avoided unless serious or life-threatening bleeding is present. Subcutaneous administration should only be considered when a patient is unable to tolerate oral vitamin K therapy yet is not clinically compromised enough to necessitate intravenous vitamin K1.7
It was noted in 1929 that chickens fed a poor diet developed spontaneous bleeding. In 1935, Dam and coworkers discovered that incorporating a fat-soluble substance defined as a "koagulation factor," into the diet could correct the bleeding. Hence the name vitamin K was developed.20,30,35
Vitamin K is an essential fat-soluble vitamin encompassing at least two distinct natural forms. Vitamin K1 (phytonadione, phylloquinone) is the only form synthesized by plants and algae. Vitamin K2 (menaquinones) is actually a series of compounds with the same 2-methyl-1, 4-naphthoquinone ring structure as phylloquinone, but with a variable number (1-13) of repeating 5-carbon units on the side chain. Bacteria synthesize vitamin K2 (menaquinones). Most of the vitamin K ingested in the diet is phylloquinone (vitamin K1).
The human daily requirement for vitamin K is small; the Food and Nutrition Board set the recommended daily allowance at 1 μg/kg/d of phylloquinone for adults, although 10 times that amount is required for infants to maintain normal hemostasis.29 Extrahepatic enzymatic reactions that are vitamin K dependent relate to carboxylation of proteins in the bone, kidney, placenta, lung, pancreas, and spleen, and include the synthesis of osteocalcin, matrix Gla protein, plaque Gla protein, and one or more renal Gla proteins.29,30,34 Variations in an individual's dietary vitamin K intake while receiving therapeutic oral anticoagulation can significantly result in either over- or under-anticoagulation.1,13
Dietary vitamin K in the forms of phylloquinone and menaquinones is solubilized in the presence of the bile salts, free fatty acids, and monoglycerides, which enhance absorption. Vitamin K is incorporated into chylomicrons, entering the circulation through the lymphatic system in transit to the liver.30 In the plasma, vitamin K is primarily in the phylloquinone form, whereas liver stores are 90% menaquinones and 10% phylloquinone.30 Within 3 days of a low ...