Vitamin K Dose For High Inr

Enhancing Healthcare Team Outcomes

Even though there is no toxic dose noted in the literature, patients should not take excessive amounts of vitamin K. Instead, patients should be urged to eat a healthy balanced diet with green leafy vegetables rather than to supplement this vitamin.

Using vitamin K therapeutically requires the effort of an interprofessional healthcare team that includes clinicians, nursing staff, dieticians, and pharmacists, especially as it pertains to the treatment of coagulopathies. Patients on warfarin need to maintain a steady intake level of vitamin K in their diet to optimize warfarin dosing. Conversely, it serves as the antidote to warfarin toxicity. Pharmacists need to counsel patients regarding this topic and dispel the notion that because they are on warfarin, they should no longer eat green leafy vegetables but instead emphasize a consistent intake is the key. Nursing can perform follow-up with patients and also reinforce the points about dietary intake, and ensure that INR and other values remain in range. Any concerns should be reported to the prescriber of warfarin or vitamin K promptly so that dose and/or regimen adjustments can take place immediately if necessary. The dietician can examine the patient’s diet and recommend changes to ensure consistent intake from dietary sources. This interprofessional approach ensures optimal patient outcomes from using vitamin K when needed.

What Range Of Inrs Should Be Managed With Oral Vitamin K Therapy

The INR values at which vitamin K was administered orally varied between the studies we reviewed. However, studies that restricted enrolment to patients with INRs below 10 tended to have a greater proportion of patients with therapeutic INRs at 24 hours22,23,24,25,26,27 than did studies without such restrictions28,29.3). This evidence suggests that the use of low-dose oral vitamin K therapy should be confined to patients with INRs below 10. Among the studies that examined INR values below 10, the threshold for intervention with vitamin K ranged from 4.5 to 6.0. This included 4 RCTs involving patients with INR values between 4.5 and 10,23,24 or between 6.0 and 10.22,25 The decision to treat with oral vitamin K therapy is influenced by patient variables, including, but not limited to, the INR. However, on the basis of the RCTs reviewed, oral vitamin K would be an appropriate treatment option for an INR between 4.5 and 10.

Data Abstraction And Quality Assessment

One reviewer collected data from each eligible study using a pretested data abstraction form, and data were checked by another reviewer to assess accuracy. Disagreements were resolved by discussion, and by a third reviewer when needed. The data collected included patient characteristics , vitamin K treatment , study setting, follow-up, and outcomes. Information on risk of bias was also collected and assessed for each outcome in each included study using the Cochrane risk of bias tool for RCTs. Risk ratios and 95% confidence intervals were calculated by pooling the results from RCTs using the Mantel Haenszel method and the random effects model. Heterogeneity was assessed using the I2 index and was deemed as moderate to high with an I2> 50%. Data were analyzed using RevMan 5.3.

Two reviewers evaluated the certainty of the evidence for each outcome using the GRADE approach. The certainty of the evidence was assessed as high, moderate, low, or very low and summarized in a GRADE Evidence Profile.

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Setting Patients And Study Design

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J Thromb Haemost.

Ann Intern Med.Arch Intern Med.

What Dose Of Oral Vitamin K Therapy Is Most Appropriate

The fear of over-correcting the INR has been cited as one barrier to the widespread use of vitamin K.6 However, our review suggests that this occurs infrequently when small doses of vitamin K are administered orally. Oral doses between 1.0 mg and 2.5 mg appear to produce similar, and low, rates of over-correction .3). One study29 found that the INR fell below 2.0 in 33% of patients who received 2.0 mg of vitamin K orally, as compared with 0%16% of patients in studies in which a 1.0-mg oral dose was used. This suggests that the preferred dose for patients with INR values between 4.5 and 10 is 1.0 mg.

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Vitamin K For Reversal Of Excessive Vitamin K Antagonist Anticoagulation: A Systematic Review And Meta

Rasha Khatib, Maja Ludwikowska, Daniel M. Witt, Jack Ansell, Nathan P. Clark, Anne Holbrook, Wojtek Wiercioch, Holger Schünemann, Robby Nieuwlaat Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv 2019 3 : 789796. doi:

Proportion Of Patients Who Reached Goal Inr

Five studies provided information on the number of patients who reached goal INR values within 1 day of vitamin K administration . The pooled RR of reaching goal INR values was 1.95 in favor of vitamin K. Overall heterogeneity was high and was not explained by the different definitions of goal INR values. The certainty of the evidence was assessed as very low because of serious risk of bias primarily related to lack of blinding, serious inconsistency, and serious imprecision of the pooled estimate. Two studies also reported the number of patients who reached goal INR values after 1 week of vitamin K administration. One study reported a RR of 1.16 for goal INR ranging between 2.0 and 3.0, and a RR of 1.65 for goal INR ranging between 1.8 and 3.2. Another study reported a RR of 0.78 for goal INR ranging between 2.0 and 4.0.

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Reversal Of Overanticoagulation In Very Elderly Hospitalized Patients With An Inr Above : 24

• Université Paris Descartes, INSERM U. 765, Paris, FranceService d’Hématologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France
• Isabelle Gouin-ThibaultCorrespondenceRequests for reprints should be addressed to Isabelle Gouin-Thibault, PhD, Faculté des Sciences Pharmaceutiques et Biologiques, Hématologie, 4 avenue de l’Observatoire, Paris 75006, FranceUniversité Paris Descartes, INSERM U. 765, Paris, FranceService d’Hématologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel Dieu, Paris, France

What Is The Risk Of Bleeding Or Thrombosis If Vitamin K Is Given

Convincing evidence that oral vitamin K therapy reduces the risk of bleeding is not yet available. Similarly, although widely discussed, there is no evidence that transient vitamin K-associated over-correction of the INR causes thrombosis. In the 8 studies reviewed, only one thrombotic event was described among the 344 patients who received oral, subcutaneous or intravenous vitamin K therapy. This patient had a myocardial infarction 3 days after receiving 1 mg of vitamin K orally.23

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Is Oral Vitamin K Therapy Effective Compared With Other Management Approaches

Four RCTs compared oral vitamin K therapy with placebo or with other methods of vitamin K administration .22,23,24,25 Two double-blind, placebo-controlled RCTs demonstrated that oral vitamin K therapy reduces the INR more promptly than does the withholding of warfarin alone.22,23 Despite the evidence that oral vitamin K therapy is effective, chart reviews and physician surveys have shown that physicians prefer to administer vitamin K subcutaneously.30,31,32 This preference exists despite evidence from randomized trials that the subcutaneous route is less effective than either the oral24 or intravenous route.33,34 The only RCT comparing oral and subcutaneous vitamin K administration showed that patients who received vitamin K orally were significantly more likely than those treated by subcutaneous injection to have a therapeutic INR on the day following treatment .24 The evidence supporting oral administration of vitamin K was further strengthened by a recent RCT that demonstrated an equivalent ability of oral and intravenous vitamin K therapies to return a prolonged INR to the therapeutic range at 24 hours.25 The intravenous route resulted in an immediate effect, as compared with a lag time of 4 hours with the oral route.25 Despite this, the intravenous route is not the preferred route of administration because its use is associated with a low but finite risk of anaphylactoid reactions.35

Risk Of Bias And Synthesis Of Results

Overall, the risk of bias of the included studies was low. All studies randomly allocated patients using proper sequence generation, and 4 of the studies reported methods of allocation concealment. Blinding of patients and outcome assessors was reported in 2 studies only. Incomplete data were limited or properly dealt with across all studies. Forest plots present a summary of the risk of bias for each study.

Subgroup analyses by vitamin K dose and method of vitamin K administration were prespecified, but identified data were inadequate to perform subgroup analyses. Publication bias was prespecified but could not be assessed given the small number of included studies.

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Vitamin K Dosage And Daily Intake Recommendations

How much vitamin K should you take? You might be surprised to learn that experts say there’s no easy answer.

Recommendations for oral dosages of vitamin K depend on the condition and can also be controversial. For example, 100-200 µg/day has been suggested as a dose to stabilize clotting times in patients for people taking anticoagulant drugs as a result of some studies. However, other researchers have challenged these results.

Experts also caution that too much vitamin K could interfere with anticoagulant drug activity. In fact, 1-5 mg of vitamin K is typically given to counteract the effects of too much warfarin a common anticoagulant drug. People taking anticoagulant drugs should not take vitamin K at any dosage level without talking to their doctor.

Reversal Of Warfarin Effects

Omit 1-2 doses, or hold warfarin monitor INR and adjust warfarin dose accordingly

INR 4.5-10, no bleeding: 2012 ACCP guidelines suggest against routine use 2008 ACCP guidelines suggest considering vitamin K1 1-2.5 mg PO once

INR > 10, no bleeding: 2012 ACCP guidelines recommend vitamin K1 PO 2008 ACCP guidelines suggest 2.5-5 mg PO once INR reduction observed within 24-48 hr, monitor INR and give additional vitamin K if needed

Minor bleeding, any elevated INR: Consider 2.5-5 mg PO once may repeat if needed after 24 hr

Major bleeding, any elevated INR: 2012 ACCP guidelines recommend prothrombin complex concentrate, human plus vitamin K1 5-10 mg IV

NOTE: High vitamin K doses may cause warfarin resistance for a week or more consider using heparin, LMWH, or direct thrombin inhibitors to provide adequate thrombosis prophylaxis in clinical conditions requiring chronic anticoagulation therapy

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Patient Safety And Education

Clinical practice guidelines developed by the American College of Chest Physicians recommend educating and involving patients on INR testing, follow up, and result and dosing decisions that increase clinical benefit and cost-effectiveness. Also, intensive patient education has been proposed to reduce adverse events related to anticoagulation. However, no clinical trial has been conducted to date.

How To Treat A Patient Whose Inr Is Too High

This content was published in 2009. We do not recommend that you take any clinical decisions based on this information without first ensuring you have checked the latest guidance.

Oral vitamin K antagonist anticoagulants are prescribed for around 500,000 patients in the UK at any one time1. They are used for several indications, including thromboprophylaxis for patients with atrial fibrillation, or who have undergone a mechanical heart valve replacement or had deep vein thrombosis . They are also used to treat current DVTs or pulmonary emboli.

Appropriate management of warfarin therapy requires monitoring of patients international normalised ratios . While pharmacists often monitor their patients INRs, it is usually doctors who manage patients who have become over- anticoagulated. Nonetheless, pharmacists may need to refer patients for treatment to reverse over-anticoagulation, so a clear understanding of how such patients are managed is essential. It also helps to understand the subsequent care of patients who have undergone warfarin reversal treatment.

Warfarin use is associated with an increased risk of haemorrhage. The precise incidence of haemorrhage due to excessive anticoagulation is difficult to measure, possibly due to variance in how bleeding is classified when treated in different clinical settings. Studies suggest that nearly 1% of haemorrhage cases are fatal2. Oral anticoagulants are, therefore, considered to be a significant potential risk to patient safety.

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Vitamin Of Coagulation Vitamin K

The first observations on K vitamins action, namely massive bleeding into the subcutaneous tissue, muscles and other organs, were observed in the 1920s and 1930s in animals fed with cholesterol/fat-deficient food. Subsequent feeding with plant products developed a curative effect. During the same period, an outbreak of a cows diseases in the northern part of the USA and Canada was found to be associated with consumption of moldy silage from Melilotus by the animals with clinical signs identical to the previously described hemorrhagic diathesis of chickens . In 1939, a group of researchers, under the supervision of the Swiss scientist Karrer, for the first time separated vitamin K1 from the plant alfalfa , under the chemical name of phylloquinone, which is a fat soluble polycyclic aromatic ketone, stable to air and moisture but decomposes in sunlight. The same year, the American biochemists Binkley and Doisy managed to isolate from the spoilt fish-flour the vitamin K2 or menaquinone with similar to vitamin K1 anti-hemorrhagic properties, but with different absorption profile and a more complex range of activity. Apart from the natural K-Vitamins , there are a number of naphthoquinone derivatives, which are acquired synthetically and possess similar anti-coagulative effect .

Reasons for Vitamin K-deficiency in humans can vary . In current clinical practice it is very useful to determine the cause of coagulopathy before appropriate treatment is administered.

Fig. 1

Normal And Critical Findings

For normal patients who are not on anticoagulation, the INR is usually 1.0 regardless of the ISI or the particular performing laboratory. For patients who are on anticoagulant therapy, the therapeutic INR ranges between 2.0 to 3.0. INR levels above 4.9 are considered critical values and increase the risk of bleeding. The therapeutic INR range differs in a patient with prosthetic valve:

• For patients with an On-X mechanical bileaflet aortic valve with no other risk factors for thromboembolism, the INR goal is 2 to 3 for the first three months after valve surgery and after three months the goal is 1.5 to 2.
• For patients with a bileaflet or current generation, single-tilting disk, mechanical, aortic, prosthetic valve with no other risk factors for thromboembolism, the target INR is 2.5.
• For patients with a mechanical aortic prosthetic valve and an additional risk factor for thromboembolic events or an older generation mechanical aortic valve prosthesis , the INR goal is 3.
• For patients with a mechanical mitral prosthetic valve or mechanical tricuspid prosthetic valve, the target INR is 3.

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Study Design And Population

This single-centre, registry study was approved by the Regional Ethical Review Board in Lund, Sweden , and was conducted in compliance with the Declaration of Helsinki. The study was performed at a nine-bed general ICU at Lund University Hospital from September 2013 to May 2019, and the manuscript was written according to the STROBE guidelines for observational studies .

PT analysis was performed using the Owren PT-INR, which is calibrated using reference plasma samples from Equalis . The normal reference range is 0.901.20, with a coefficient of variation of < 5%. The Owren method is only affected by variations of coagulation factors II, VII and X, as compared to Quick-PT also affected by fI and fV.

For comparison, patients with PT-INR in the range of 1.31.9 not given vitamin K were included. These were defined as patients with prolonged PT-INR at their initial sampling with a follow-up sample within 1236h . The groups are referred to as the Vitamin K group and the control group respectively.

A schematic flow chart of the study design is shown in Fig. .

Fig. 1

Severe sepsis and septic shock were classified according to the Sepsis 2 definition because the majority of the data were collected from a time period prior to the establishment of the Sepsis 3 diagnosis criteria.

The expected mortality rate calibrated for Swedish ICUs was computed based on the simplified acute physiology score via a formula previously described .