An emerging epidemic of allergic contact dermatitis due to phytonadione epoxide (oxidised vitamin K1).

BACKGROUND: Reports of allergic contact dermatitis (ACD) to phytonadione epoxide (PE) in cosmetics suggest that PE is as powerful a sensitiser as its parent compound phytonadione. OBJECTIVE: To evaluate a case series of ACD to PE in Spain. METHODS: We reviewed the records of 20 patients with ACD to cosmetics containing PE diagnosed across Spain between January 2019 and June 2023. RESULTS: All 20 patients developed patch test (PT) or repeated open application test (ROAT) reactions to cosmetics containing PE. All involved women with eyelid eczema. PT or ROAT with PE preparations were positive in 17/20 (85%). PE at 1%, 5%, 10% and 20% in pet. was patch-tested in 8/17, 14/17, 11/17 and 8/17 patients; being positive in 6/8 (75%), 13/14 (92.85%), 11/11 (100%) and 8/8 (100%), respectively. CONCLUSION: Regulators should, not only ban the specific dangerous cosmetic ingredients, but also consider to ban or keep under close surveillance those closely related products or derivatives that might potentially cause similar harmful effects. PTs with PE are suggested to be performed at a 5% concentration in pet. Higher concentrations (10% pet.) should be tested whenever PTs with 5% pet. PE are negative.

Evaluation of Response to High-Dose Intravenous Vitamin K Administration.

BACKGROUND: Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing. OBJECTIVE: This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies. METHODS: This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study. RESULTS: There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed. CONCLUSIONS: In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.

Vitamin K Deficiency Bleeding: An Ounce of Prevention.

Vitamin K is a fat-soluble vitamin essential for the formation of factors in the clotting cascade. Newborns are born with insufficient levels of vitamin K, resulting in high risk for vitamin K deficiency bleeding (VKDB). Vitamin K deficiency bleeding can occur in the first week of life ("classic" VKDB) and also between 2 weeks and 3 months of age ("late" VKDB). Vitamin K deficiency bleeding can present as bleeding in the skin or gastrointestinal tract, with as many as half of affected neonates experiencing intracranial bleeding. A single intramuscular injection of vitamin K effectively prevents both classic and late VKDB. Although intramuscular vitamin K is safe and effective, VKDB has reemerged because of decreased utilization. Parents refuse intramuscular vitamin K for a variety of reasons, including a disproven association with childhood cancer, the desire to avoid exposure to additives, and valid concerns about early neonatal pain. Many parents request oral vitamin K, an inferior alternative strategy that requires multiple doses utilizing products not designed for neonatal oral administration. In this setting, health care professionals must understand the epidemiology of VKDB and compassionately counsel parents to assuage concerns. Delivery of intramuscular vitamin K to all newborns remains a public health imperative, benefitting thousands of infants annually.

Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say.

Historically, coagulopathy related to cirrhosis has been managed primarily as a bleeding disorder. However, several recent studies have shown that patients with cirrhosis have an increased risk of both bleeding and clotting. These coagulopathic changes are a result of the decreased synthetic capabilities of the cirrhotic liver. Vitamin K is often given to correct prolonged prothrombin times (PT) in patients with cirrhosis. However, this practice is not well defined and its effectiveness is questionable. The objective of our literature review is to determine the effectiveness of vitamin K to correct coagulopathy in cirrhosis. This report evaluates data published between 1981 and 2017. Published articles relevant to vitamin K use in cirrhotic patients were reviewed and summarized. The available literature regarding the use of vitamin K in cirrhosis is limited, and the research published so far does not appear to support its use. The routine uses of vitamin K to correct PT/international normalized ratio in hepatic cirrhosis should be avoided unless further studies can demonstrate true clinical benefit.

Administration of Injectable Vitamin K Orally.

Background: Vitamin K, or phytonadione, is available in both injectable and oral formulations. Oral vitamin K is available as 5-mg tablets, but the key drawbacks for using vitamin K tablets consist of availability of only 1 dose strength and recent tripling of the product's cost over a 2-year period. An interest exists for utilization of injectable vitamin K via oral route. Method: A literature search was performed on April 26, 2017, to identify any studies describing the use of injectable vitamin K for oral administration. The search involved PubMed and Embase and utilized various combinations of keywords vitamin K, phytonadione, IV, intravenous, injectable, and oral. The results were limited to studies that discussed oral administration of injectable vitamin K. The efficacy of the injectable preparation of vitamin K administered orally was explored in 6 studies and one cost-savings project. Results: Based on the available literature, the administration of injectable vitamin K via oral route is effective and safe. Injectable vitamin K for oral administration can be prepared as an undiluted solution or as a compounded solution. These 2 formulations have different beyond-use dates depending on ingredients used. Conclusion: Information on efficacy and stability of injectable vitamin K formulations prepared for oral administration provides an additional option for health care systems when vitamin K tablets are unavailable or cost-prohibitive to use.

An evaluation of intravenous vitamin k for warfarin reversal: are guideline recommendations being followed?

BACKGROUND: Vitamin K antagonists (eg, warfarin) remain the mainstay of anticoagulation therapy in the United States, with over 22 million prescriptions being filled annually. Unfortunately, warfarin therapy is difficult to manage and increases bleeding risk. The 2012 American College of Chest Physicians guidelines created a warfarin reversal algorithm that suggested the stringent use of intravenous vitamin K. OBJECTIVE: The purpose of this evaluation was to determine the rates of adherence with guideline recommendations in clinical practice. METHOD: A convenience sample of 3 months of intravenous vitamin K medication administration data (September to November 2013) was obtained to conduct a retrospective review. Patients with underlying hepatic dysfunction or lack of warfarin therapy were excluded. Vitamin K use was evaluated for consistency with the 2012 guidelines. RESULTS: A total of 364 patients were reviewed and 119 were included. Vitamin K utilization was consistent with guideline recommendations for a total of 30 (25.2%) patients. The most common site of active bleeding requiring reversal was head bleeds, consisting of 56.6% of bleeds. A single dose of 10 mg of vitamin K was the most frequently used dosing strategy. Fresh frozen plasma (73.3%) and four-factor prothrombin complex concentrate (36.7%) were the most commonly used factor products. CONCLUSION: This evaluation demonstrates that there is a difference between clinical judgment and guideline adherence. True adherence with the guidelines may not be necessary; however, there is room for improvement in both the appropriateness and safety of intravenous vitamin K use.

Evaluation of education on the appropriate use of vitamin k in warfarin reversal in adult inpatients.

PURPOSE: Vitamin K (phytonadione) is a commonly used first-line reversal agent for vitamin K antagonist (VKA) therapy in patients presenting with a supratherapeutic international normalized ratio (INR) with or without significant bleeding or in patients with a therapeutic INR in need of surgery. The purpose of this study was to determine the impact of education on the appropriate use of vitamin K for VKA reversal. METHODS: Data were collected on patients admitted to a community teaching hospital during February 2010 (pre-education group). These data were analyzed to determine the most common guideline deviations in vitamin K use. Following this analysis, pharmacist education took place in the form of in-service presentations; a protocol, including a guideline-based dosing table, was developed to assist pharmacists in evaluating vitamin K therapy. Data were then collected on patients admitted during February 2011 (post-education group). RESULTS: Forty patients and 47 vitamin K administrations were included in the pre-education group, and 34 patients and 49 vitamin K administrations were included in the post-education group. The number of patients with appropriate vitamin K administrations improved after pharmacist education (25% pre-education vs 55.8% post-education; P = .01). Whereas 27.6% of individual vitamin K administrations were appropriate in the pre-education group, this increased to 63.2% in the post-education group (P = .04). CONCLUSION: Education techniques on the appropriate use of vitamin K for VKA reversal significantly improved compliance with standards of care for proper use of vitamin K. Additional education sessions are necessary to further increase compliance with standards of care and subsequently optimize patient care.

Effect of Phytonadione on Correction of Coagulopathy in Pediatric Patients With Septic Shock.

OBJECTIVES: The purpose of this study was to evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC). The primary objective was to identify the number of patients with an international normalized ratio (INR), defined as ≤1.2, following phytonadione. Secondary objectives were to compare patients who achieved a normalized INR versus those with INR >1.2 and to determine factors associated with a normalized INR. METHODS: A retrospective study of children <18 years of age receiving phytonadione from October 1, 2013, to August 31, 2020, with a diagnosis of septic shock, were included. Data collection included demographics, phytonadione regimen, INR values, Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality III (PRISM III) scores, fresh frozen plasma (FFP) and cryoprecipitate use. A logistic regression model and generalized linear model were used to explore factors associated with a normalized INR and evaluate phytonadione dosing. RESULTS: Data for initial phytonadione course for 156 patients were evaluated. Sixty-six (42.3%) patients had a normalized INR. Most patients (n = 145; 92.9%) received ≤3 phytonadione doses, with the largest reduction in INR occurring after the second dose. In the logistic regression model, baseline INR, FFP, cryoprecipitate, vasopressors, PIM2, PRISM III, or cumulative phytonadione dose were not associated with achieving a normalized INR. CONCLUSIONS: Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy.

Intravenous phytonadione administered orally in reducing warfarin-related coagulopathy.

INTRODUCTION: The cost of phytonadione tablets has increased markedly and is significantly higher than the intravenous formulation. The intravenous formulation given orally is a potential alternative but has not been directly evaluated in comparison to the commercially available tablet. The objective of this study was to evaluate the efficacy of phytonadione intravenous solution given orally compared to commercially available phytonadione tablets for reversal of coagulopathy related to warfarin. METHODS: We conducted a retrospective, observational study of adult patients who received phytonadione tablets and the IV formulation orally for warfarin-related coagulopathy. The international normalized ratio (INR) was measured before and after phytonadione administration. The primary outcome was INR <1.5 at 24 h after phytonadione administration. RESULTS: From January 1, 2015 to August 1, 2018 a total of 200 patients were identified. In total, 58% (n = 116) patients received IV phytonadione solution given orally and 42% (n = 84) patients received the tablets. The primary outcome of INR <1.5 at 24 h was not significantly different between groups (p = 0.321). DISCUSSION: The IV phytonadione solution given by mouth and the tablet formulation performed similarly.

Warfarin Overdose in an Adolescent Not Dependent on Anticoagulation: Reversal Strategy and Kinetics.

INTRODUCTION: Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients. CASE REPORT: This is the report of a 15-year-old female who ingested her father's warfarin (100-200 mg) in a self-harm attempt. At hour 24 post-ingestion, her INR was 2.00 and she was admitted for monitoring. Reversal of coagulopathy was initially deferred pending the INR trend. The INR was 5.10 at hour 60 and 2.5 mg oral vitamin K1 (VK1) was given. At hour 85, the INR peaked at 6.67 and she received a second oral dose of 2.5 mg VK1. On day 8, she was medically cleared with an INR of 1.31. On day 11, she developed lower abdominal pain and diarrhea. Imaging revealed a duodenal hematoma, and symptoms improved spontaneously. She was again medically cleared 13 days post-ingestion. Her serum warfarin concentration peaked at 19 mcg/mL at hour 46. Serial warfarin concentrations were obtained, demonstrating first-order elimination kinetics and a 30-hour half-life. CONCLUSION: A restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

Appropriateness of Using Vitamin K for the Correction of INR Elevation Secondary to Hepatic Disease in Critically ill Patients: An Observational Study.

BACKGROUND: Using vitamin K for correction of coagulopathy in critically ill patients is controversial with limited evidence. This study aims to evaluate the efficacy and safety of vitamin K in the correction of international normalized ratio (INR) elevation secondary to liver disease in critically ill patients. METHOD: A retrospective study of critically ill patients with coagulopathy secondary to liver disease. The primary outcome was to evaluate the association between vitamin K administration and the incidence of new bleeding events in critically ill patients with INR elevation; other outcomes were considered secondary. Patients were categorized into two groups based on vitamin K administration to correct INR elevation. The propensity score was generated based on disease severity scores and the use of pharmacological DVT prophylaxis. RESULTS: A total of 98 patients were included in the study. Forty-seven patients (48%) received vitamin K during the study period. The odds of the new bleeding event was not statistically different between groups (OR 2.4, 95% CI 0.28-21.67, P = .42). Delta of INR reduction was observed with a median of 0.63 when the first dose is given (P-value: <.0001). However the INR reduction with other subsequent doses of vitamin K was not statistically significant. CONCLUSION: The administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events. Further studies are needed to assess the value of vitamin K administration in critically ill patients with liver diseases related coagulopathy.

Rebleeding in Variceal and Nonvariceal Gastrointestinal Bleeds in Cirrhotic Patients Using Vitamin K1: The LIVER-K Study.

BACKGROUND: Gastroesophageal varices are the most common cause of upper gastrointestinal bleeding (UGIB) in patients with cirrhosis. Vitamin K1 is commonly administered to patients presenting with UGIB and elevated international normalized ratio, despite limited evidence to support this practice. OBJECTIVES: The primary objective was to describe the incidence of rebleeding within 30 days after vitamin K1 administration in patients with cirrhosis and UGIB. The secondary objective was to describe prescribing patterns for vitamin K1. METHODS: This retrospective, descriptive multicentre study involved patients with cirrhosis and UGIB who were admitted to any of the 4 adult acute care hospitals in Calgary, Alberta, from January 1, 2014, to December 31, 2016. Patients were divided into 2 groups: those who received vitamin K1 and those who did not. RESULTS: A total of 370 patients met the inclusion criteria, of whom 243 received vitamin K1 and 127 did not. Baseline characteristics were similar between the groups. Greater proportions of patients in the vitamin K1 group received transfusions of packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate, or prothrombin concentrate during their admissions. There was no significant difference in the duration of octreotide and pantoprazole infusions. Among patients in the vitamin K1 group, there were more admissions to the intensive care unit and longer lengths of stay. More patients in the no vitamin K1 group had esophageal varices evident on endoscopy that required endoscopic treatment. Forty of the patients (16.5%) in the vitamin K1 group and 7 (5.5%) in the no vitamin K1 group had rebleeding within 30 days of the initial bleed. The median total vitamin K1 dose administered was 25 mg. CONCLUSIONS: The study results suggest that vitamin K1 does not reduce the incidence of rebleeding within 30 days of the initial bleed in patients with cirrhosis and UGIB.

CONTEXTE: Les varices oesophagiennes sont la cause la plus fréquente de l'hémorragie gastro-intestinale supérieure (HGIS) parmi les patients atteints de cirrhose. On administre communément de la vitamine K1 aux patients présentant une HGIS et dont la mesure du rapport international normalisé (RIN) est élevée, malgré le manque de preuves soutenant cette pratique. OBJECTIFS: L'objectif principal consistait à décrire la fréquence de la reprise du saignement dans les 30 jours après l'administration de la vitamine K1 à des patients atteints de cirrhose et de HGIS. L'objectif secondaire consistait à décrire les schémas de prescription de la vitamine K1. MÉTHODE: Cette étude multicentrique, descriptive et rétrospective comprenait des patients atteints de cirrhose et de HGIS, ayant été admis à n'importe lesquels des quatre hôpitaux de soins actifs pour adultes de Calgary, Alberta, du 1er janvier 2014 au 31 décembre 2016. Les patients étaient répartis en deux groupes : ceux ayant reçu de la vitamine K1 et ceux n'en ayant pas reçu. RÉSULTATS: Le nombre total de 370 patients correspondait aux critères d'inclusion. Parmi ceux-ci, 243 avaient reçu de la vitamine K1 et 127 n'en n'avaient pas reçu. Les caractéristiques de base étaient similaires entre les groupes. Un plus grand nombre de patients du groupe « Vitamine K1 "avaient reçu une transfusion d'un concentré de globules rouges, de plasma frais congelé, de plaquettes, de cryoprécipité ou de concentré de prothrombine au cours de leur séjour hospitalier. On n'a noté aucune différence significative dans la durée des injections de pantoprazole et d'octréotide. Le nombre d'admissions de patients du groupe « Vitamine K1 ¼ à l'unité de soins intensifs était plus élevé et le séjour de ceux-ci était plus long. L'endoscopie a montré qu'un plus grand nombre de patients du groupe « Sans vitamine K1 ¼ présentaient des varices oesophagiennes nécessitant un traitement endoscopique. Dans les 30 jours après le saignement initial, quarante (16,5 %) patients du groupe « Vitamine K1 ¼ et 7 (5,5 %) du groupe « Sans vitamine K1 ¼ ont subi une nouvelle hémorragie. La dose moyenne totale de vitamine K1 administrée était de 25 mg. CONCLUSIONS: Les résultats de l'étude tendent à démontrer que la vitamine K1 ne réduit pas la fréquence de la reprise du saignement dans les 30 jours qui suivent le saignement initial parmi les patients atteints de cirrhose et de HGIS.

Characterizing the Severe Reactions of Parenteral Vitamin K1.

Parenteral vitamin K1 (phytonadione) is used for anticoagulant reversal, and a boxed warning exists with intravenous and intramuscular administration due to the possibility of severe reactions, including fatalities. These reactions resemble hypersensitivity or anaphylaxis, including anaphylactoid reaction, and have led to shock and cardiac and/or respiratory arrest. The objective of this review is to summarize the available literature detailing the anaphylactic/anaphylactoid reactions with parenteral vitamin K1 in order to better characterize the reaction and provide a more in-depth understanding of its importance. A comprehensive literature search of MEDLINE (1946 to June 2016) and EMBASE (1947 to June 2016) was conducted using the terms vitamin K1, phytonadione, phytomenadione, vitamin K group, anaphylaxis, polyoxyethylated castor oil, and cremophor. A total of 2 retrospective surveillance studies, 2 retrospective cohort studies, and 17 case reports were identified for inclusion and assessment. Based on a review of the literature, use of parenteral vitamin K1 may result in severe hypotension, bradycardia or tachycardia, dyspnea, bronchospasm, cardiac arrest, and death. These reactions are most consistent with a nonimmune-mediated anaphylactoid mechanism. It appears that intravenous administration is more frequently associated with these reactions and occurs at an incidence of 3 per 10 000 doses of intravenous vitamin K1. The solubilizer may also increase the risk of adverse reactions, which occurred in patients with and without previous exposure to vitamin K1. Although there are known factors that increase the risk of an adverse drug event occurring, reactions have been reported despite all precautions being properly followed.

The effectiveness of intravenous vitamin K in correcting cirrhosis-associated coagulopathy.

OBJECTIVES: The goal of this study was to evaluate the effectiveness of intravenous (IV) vitamin K in cirrhosis. METHODS: This was a retrospective study of cirrhotic patients, not on anticoagulation, with administration of IV vitamin K and a baseline INR > 1.5. The primary outcome was the effectiveness of therapy defined by a 30% decrease in INR or a reduction in INR to an absolute value of ≤1.5. KEY FINDINGS: A total of 96 patients were included in the cohort. There was an average decrease in INR of 0.31; however, 60 patients (62.3%) failed to achieve at least a 10% decrease. Sixteen patients (16.7%) met the primary effectiveness endpoint. CONCLUSIONS: The use of IV vitamin K to correct coagulopathy of cirrhosis may not be beneficial.

A sensitive and rapid UFLC-APCI-MS/MS bioanalytical method for quantification of endogenous and exogenous Vitamin K1 isomers in human plasma: Development, validation and first application to a pharmacokinetic study.

Due to lack of suitable bioanalytical methods in previous literature, for simultaneous estimation of Vitamin K1 isomers, in compliance with the current regulatory expectation, we aimed to develop a sensitive and rapid method with UFLC-APCI-MS/MS (ultrafast liquid chromatography - tandem mass spectrometry) using human plasma. A simple and cost effective procedure was implemented with the combination of protein precipitation and liquid extraction, to isolate the targets from plasma sample, while achieving an insignificant matrix effects and high recovery (≥88.2%). A short 9.0min run time per sample was accomplished by using water in methanol (1.0% v/v) and acetonitrile, which pumped at 0.8mL/min, on to the COSMOSIL® packed column, for separating the trans and cis isomers of Vitamin K1 along with the corresponding stable labeled D7 internal standards (ISs). The analytes and ISs were quantified, at their parent to product ion mass transitions of 451.3 →187.1m/z and 458.1→194.3m/z respectively, using an APCI (atmospheric pressure chemical ionization) source of the tandem mass, in MRM (multiple reaction monitoring) mode. Performance of the method over the calibration range: 0.1-150.0ng/mL, while using a low sample volume (0.3mL), was successfully evaluated through full method validation in compliance with the latest regulations. Fully validated method with significant results was applied to human pharmacokinetic study, and had a potential to further advance the clinical research programs and generic drug development of Vitamin K1, intended for the regulatory submission.

Phytonadione Content in Branded Intravenous Fat Emulsions.

BACKGROUND: Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. MATERIALS AND METHODS: Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. RESULTS: Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity ( r = 0.99), and accuracy (coefficient of variation <5%). CONCLUSIONS: Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.

Management of Supratherapeutic International Normalized Ratio without Bleeding after Warfarin Use: An Evaluation of Vitamin K Administration (SUPRA-WAR-K Study).

BACKGROUND: For patients with supratherapeutic international normalized ratio (INR) and no evidence of bleeding, the 2012 guidelines of the American College of Chest Physicians discourage administration of vitamin K. At the study hospital, it was observed that vitamin K was frequently prescribed for patients with INR of 4.5 or higher and no bleeding. OBJECTIVES: To compare efficacy and safety outcomes between holding warfarin alone and holding warfarin with administration of vitamin K and to compare these outcomes among various doses and routes of vitamin K administration in non-critical care inpatients experiencing supratherapeutic INR without evidence of bleeding. METHODS: This single-centre retrospective chart review involved noncritical care inpatients with supratherapeutic INR (4.5-8.9) without evidence of bleeding. The primary outcomes were the change in INR 1 day after implementation of supratherapeutic INR management and the time to reach INR less than 3.0. The secondary outcomes were length of stay, frequency of warfarin resistance, incidence and duration of bridging anticoagulation, incidence of thromboembolism and major bleeding, and death. RESULTS: Regardless of vitamin K dose, the administration of vitamin K combined with holding warfarin, relative to holding warfarin alone, was associated with a greater INR decrease 1 day after the intervention (mean ± standard deviation -3.2 ± 1.9 versus -0.9 ± 1.0, p < 0.001) and a shorter time to reach INR below 3.0 (1.9 ± 1.0 days versus 2.6 ± 1.4 days, p = 0.003). No statistically significant differences in any other outcomes were observed. CONCLUSIONS: In hospitalized non-critical care patients with INR between 4.5 and 8.9 without evidence of bleeding, the combination of holding warfarin and administering vitamin K was associated with greater and faster decreases in INR than holding warfarin alone. No significant differences were found in clinically important outcomes. The practice of administering vitamin K in this population warrants further study and re-evaluation.

CONTEXTE: Dans ses lignes directrices de 2012, l'American College of Chest Physicians déconseille l'administration de vitamine K aux patients ayant des résultats de rapport international normalisé (RIN) suprathérapeutiques et ne présentant aucun saignement. À l'hôpital des auteurs, on a remarqué que l'on prescrivait fréquemment de la vitamine K aux patients répondant aux critères ci-dessus. OBJECTIFS: Comparer l'efficacité et l'innocuité entre un simple arrêt de la warfarine et l'arrêt de la warfarine combiné à l'administration de vitamine K, puis comparer ces résultats thérapeutiques selon différentes doses et voies d'administration de la vitamine K chez des patients hospitalisés qui ne sont pas en phase critique, qui ont un RIN suprathérapeutique et qui ne présentent aucun saignement. MÉTHODES: La présente étude menée dans un seul centre comportait une analyse des dossiers médicaux de patients hospitalisés n'étant pas en phase critique, ayant un RIN suprathérapeutique (4.5­8.9) et ne présentant aucun saignement. Les principaux paramètres d'évaluation étaient le changement du RIN un jour après la mise en œuvre de mesures pour corriger un RIN suprathérapeutique et le temps nécessaire pour atteindre un RIN de moins de 3,0. Les paramètres d'évaluation secondaires étaient la durée du séjour, la fréquence des cas de résistance à la warfarine, le nombre et la durée des relais anticoagulants, l'incidence des cas de thromboembolie et de saignement important et les cas de décès. RÉSULTATS: L'administration de vitamine K, peu importe la dose, combinée à l'arrêt de la warfarine comparativement au simple arrêt de la warfarine était associée à une réduction plus importante du RIN un jour après l'intervention (moyenne ± écart-type −3.2 ± 1,9 contre −0,9 ± 1,0, p < 0,001) et à un plus court délai pour atteindre un RIN de moins de 3,0 (1,9 ± 1,0 jour contre 2,6 ± 1,4 jours, p = 0.003). Aucune différence statistiquement significative n'a été observée pour le reste des paramètres d'évaluation. CONCLUSIONS: Chez les patients hospitalisés n'étant pas en phase critique, ayant un RIN entre 4,5 et 8,9 et ne présentant aucun saignement, l'arrêt de la warfarine combiné à l'administration de vitamine K a été associé à une réduction plus rapide et plus importante du RIN que le simple arrêt de la warfarine. On n'a observé aucune différence significative en ce qui touche aux résultats thérapeutiques cliniquement importants. L'administration de vitamine K pour cette population est une pratique qui nécessite de plus amples études et doit être évaluée à nouveau.