StatPearls [Internet].
Persevering with Schooling Exercise
Vitamin K is a medicine used within the administration and therapy of bleeding as a result of coagulation dysfunction attributable to warfarin and vitamin K deficiency. It’s within the fat-soluble vitamin class of medication. This exercise outlines the indications, motion, and contraindications for vitamin K as a worthwhile agent within the administration of coagulation problems attributable to warfarin or vitamin K deficiency.
Targets:Establish the mechanism of motion of vitamin K.Describe the hostile results and contraindications of vitamin K.Clarify the significance of vitamin K regarding monitoring for sufferers on warfarin remedy, together with goal INR ranges. Define interprofessional staff methods for bettering care coordination and communication for bettering outcomes with bleeding utilizing vitamin K.Earn persevering with training credit (CME/CE) on this subject.
Indications
Vitamin K is a fat-soluble vitamin that impacts coagulation pathways inside the physique. Vitamin K is present in meals and could be a dietary complement. Vitamin K is crucial for the synthesis of coagulation proteins. It’s a co-factor for vitamin K dependent carboxylation, which incorporates varied enzymes. The method of vitamin K carboxylation permits the coagulation elements to bind calcium ions, which additional facilitates the cascade pathways. Vitamin K deficiency impairs the coagulation course of resulting in points with bleeding. Current analysis has linked vitamin K deficiency to points with osteoporosis and cystic fibrosis.[1][2]
Vitamin K happens in two bioactive varieties, vitamin K1 and vitamin K2. Vitamin K1, also called phylloquinone, is a product of plant synthesis. It’s most prevalent in inexperienced leafy greens as a result of it’s straight concerned in photosynthesis. Vitamin K1 is lively in animals and is answerable for the manufacturing of coagulation elements. It additionally will be transformed into vitamin K2 in animals.[2][3][4][5]
Vitamin K2 is created within the intestine by micro organism. Intestine flora converts vitamin K1 into vitamin K2 (menaquinone). A variety of vitamin K2 varieties will be created. This transformation takes place through the intestine micro organism lengthening the isoprenoid facet chain. Micro organism are the first producers of menaquinones, which they use throughout anaerobic respiration. They differ in construction from phylloquinone as a result of 3-substituted lipophilic facet chain. Most vital types of menaquinones comprise 4 to 10 repeating isoprenoid models. These are indicated by MK-4 to MK-10. Probably the most notable varieties embrace MK-7 to MK-11. The MK-7 and different bacterially derived types of vitamin K2 exhibit vitamin K exercise in animals. The artificial sort of vitamin K, vitamin K3 (menadione), interferes with glutathione, which causes toxicity to animals. Because of this, vitamin K3 is now not a viable therapy for vitamin K deficiency.[2][6][7][8]
Mechanism of Motion – “k vitamin overdose”
The first operate of vitamin K2 is including carboxylic acid teams to glutamate residues (Glu) to type gamma-carboxyglutamate residues (Gla) through the creation of clotting elements. The presence of two carboxylic acid teams on a single carbon that resides within the gamma-carboxyglutamate residue permits for the chelation of calcium ions. The binding of calcium ions on this vogue is of essential significance for vitamin K-dependent clotting elements, allowing the perpetuation of the clotting cascades. Vitamin K can be answerable for the synthesis of prothrombin, issue VII, issue IX, and issue X.[1][9]
Vitamin K turns into diminished within the cell to a metabolic type referred to as vitamin K hydroquinone. The catalyst for this course of is the enzyme vitamin K epoxide reductase (VKOR). Subsequently, vitamin K hydroquinone will get oxidized by gamma-glutamyl carboxylase (also called vitamin K-dependent carboxylase). This enzyme carboxylates Glu to Gla, finally creating vitamin K epoxide. The carboxylation and epoxidation reactions are supposed coupled (occurring concurrently). Subsequent, vitamin K epoxide is reconverted to vitamin K by VKOR. This complete course of has the identify of the vitamin K cycle. Vitamin K1 deficiency is just not widespread in people as a result of it consistently recycles inside cells.[1][10][11]
Warfarin is a compound used for anticoagulation that blocks the motion of VKOR and ends in decreased quantities of vitamin K and vitamin K hydroquinone, which prevents any effectivity by the glutamyl carboxylase enzyme and prevents the carboxylation response from occurring. In consequence, clotting elements get produced with out an ample variety of Gla amino termini. These ‘inactive” elements can now not create steady bonds to blood vessels endothelium; due to this fact, no clot formation will consequence even after endothelial damage. In conclusion, the enzymes that take part within the vitamin K cycle embrace gamma-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKOR), and an as-yet-unidentified vitamin K reductase (VKR). Vitamin K is a lipophilic compound and leads the idea that Vitamin K cycle enzymes are integral membrane proteins that reside within the endoplasmic reticulum. Mutations in these enzymes consequence within the affected person that possesses bleeding problems or resistance to anticoagulation.[1][11][12]
Administration
The popular selection for oral vitamin K supplementation is vitamin K1. The prompt dose is 1 to 2 mg. In circumstances of extreme coagulopathy (i.e., excessive INR), an oral dose of 5 to 10 mg will be administered. The utmost oral dose is 25 mg. Alternatively, vitamin K1 will be given intravenously. The dose for intravenous administration is 10 to twenty mg. It ought to be given slowly (a minimum of 30 min). The impact often happens inside 2 to 4 hours after administering an intravenous dose. The utmost impact for intravenous administration is 6 to 12 hours, whereas oral supplementation will take about 24 hours. [13]
Opposed Results
Presently, there is no such thing as a recognized toxicity is related to excessive doses of vitamin K1 or vitamin K2. Subsequently, there is no such thing as a designated higher consumption degree (UL). Regardless of this, an allergic response is feasible with both model of vitamin K. Vitamin K1 has had documented associations with bronchospasm and cardiac arrest with IV administration. The oral type of vitamin K doesn’t appear to trigger extreme reactions.[14][15]
Vitamin K2 additionally doesn’t show any hostile results when ingested orally. Research have proven that coagulation research in people didn’t present an elevated danger of blood clots when ingesting 45 mg per day of vitamin K2 (as MK-4). Researchers noticed this in a affected person who took upwards of 135 mg per day (45 mg thrice per day).[16][17]
The artificial vitamin K3 could be very poisonous, and consequently, has been banned from over-the-counter gross sales in america as a result of ingestion may lead to allergic reactions, hemolytic anemia, and cytotoxicity in liver cells.[2]