Belgian Consensus Recommendations to Prevent Vitamin K Deficiency Bleeding in the Term and Preterm Infant.

Neonatal vitamin K prophylaxis is essential to prevent vitamin K deficiency bleeding (VKDB) with a clear benefit compared to placebo. Various routes (intramuscular (IM), oral, intravenous (IV)) and dosing regimens were explored. A literature review was conducted to compare vitamin K regimens on VKDB incidence. Simultaneously, information on practices was collected from Belgian pediatric and neonatal departments. Based on the review and these practices, a consensus was developed and voted on by all co-authors and heads of pediatric departments. Today, practices vary. In line with literature, the advised prophylactic regimen is 1 or 2 mg IM vitamin K once at birth. In the case of parental refusal, healthcare providers should inform parents of the slightly inferior alternative (2 mg oral vitamin K at birth, followed by 1 or 2 mg oral weekly for 3 months when breastfed). We recommend 1 mg IM in preterm <32 weeks, and the same alternative in the case of parental refusal. When IM is perceived impossible in preterm <32 weeks, 0.5 mg IV once is recommended, with a single additional IM 1 mg dose when IV lipids are discontinued. This recommendation is a step towards harmonizing vitamin K prophylaxis in all newborns.

Avoidance of Vitamin K-Rich Foods Is Common among Warfarin Users and Translates into Lower Usual Vitamin K Intakes.

BACKGROUND: Warfarin users should aim for stable daily vitamin K intakes. However, some studies report that patients are often advised to avoid eating green vegetables. Whether this advice impacts vitamin K intakes is unknown. OBJECTIVE: Our aim was to describe the nature and sources of vitamin K-related dietary recommendations that patients received at the initiation of warfarin therapy, assess their adherence to these recommendations, and examine whether usual vitamin K intakes vary according to these recommendations. DESIGN: We conducted a retrospective cohort study with patients enrolled in the Québec Warfarin Cohort Study. Patients were asked to report dietary recommendations they had received at warfarin initiation and their adherence to these recommendations. Usual vitamin K intakes were assessed using a validated semi-quantitative food frequency questionnaire. PARTICIPANTS/SETTING: Three hundred seventeen patients aged 36 to 97 years who initiated warfarin between 2011 and 2012 and were treated for 12 months or longer with a target international normalized ratio range of 2.0 to 3.0 or 2.5 to 3.5. STATISTICAL ANALYSES PERFORMED: Patients were classified according to vitamin K-related recommendations reported: limit or avoid vitamin K-rich foods; aim for stable consumption of vitamin K-rich foods; or no vitamin K-related advice. A one-way analysis of covariance was used to compare mean usual vitamin K intakes between patients after adjustment for covariates. RESULTS: Most patients (68%) reported being advised to limit or avoid vitamin K-rich foods, particularly green vegetables, 10% reported being advised to aim for stable consumption of vitamin K-rich foods, and 22% did not recall receiving any vitamin K-related recommendation. Mean usual vitamin K intakes of patients adhering to the recommendation to limit or avoid vitamin K-rich foods was 35% to 46% lower than those of other patients (P<0.001), a difference resulting almost entirely (82%) from a lower consumption of green vegetables. CONCLUSIONS: In contrast with current dietary recommendation, most warfarin users reported avoiding vitamin K-rich foods, which translated into lower usual vitamin K intakes.

Supratherapeutic international normalized ratio due to reduced vitamin K intake secondary to prolonged vomiting in a patient on warfarin.

OBJECTIVE: To report a case of prolonged vomiting during warfarin therapy, leading to an elevated international normalized ratio (INR). CASE SUMMARY: A 32-year-old female with a history of cyclic vomiting syndrome since early childhood and bilateral pulmonary emboli diagnosed 4 months prior to this acute event presented to the clinic for routine monitoring of warfarin therapy. The warfarin dose had been maintained at 35 mg/wk for 3½ months (INR 2-3.5), but it was increased to 37.5 mg/wk because the INR had trended down to the low goal range over the preceding month. At presentation, the patient reported a 15-day history of vomiting with minimal oral intake that required intravenous fluids to prevent dehydration. The INR was 4.7; warfarin was withheld, and oral vitamin K 5 mg as well as subcutaneous vitamin K 10 mg was administered the following day. The INR then decreased to 1.3. Therapy was transitioned to subcutaneous enoxaparin 1 mg/kg every 12 hours for the duration of the patient's anticoagulation therapy. DISCUSSION: Multiple reports have demonstrated malabsorption of warfarin and decreased INR response in the presence of underlying gastrointestinal disease. Despite a prolonged episode of cyclic vomiting syndrome, our patient had an elevated INR. In normal circumstances, warfarin is rapidly absorbed from the gastrointestinal tract and reaches maximum serum concentrations in approximately 90 minutes. Studies have shown that although the presence of food does not affect overall absorption of the medication, it can decrease the rate of absorption. Our patient was vomiting 20-30 minutes after oral dose administration. Because the patient was not consuming food, absorption of warfarin was potentially prompt, thus contributing to the elevated INR. The variability of vitamin K in the diet also can have significant impact on the response to warfarin. Our patient's INR had been stable while she consumed 3 servings each week of foods rich in vitamin K. This consumption was abruptly discontinued with the onset of the cyclic vomiting syndrome. We believe that decreased intake and retention of oral vitamin K-containing foods from the diet due to the prolonged vomiting coupled with the rapid onset of absorption resulted in a notably increased INR and subsequent bruising in our patient. CONCLUSIONS: In the presence of prolonged vomiting, warfarin therapy requires more frequent monitoring than usual to detect fluctuations in INR that may increase the risk of adverse events.

The use of vitamin K in patients on anticoagulant therapy: a practical guide.

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

Upper limits of vitamin A in infant formulas, with some comments on vitamin K.

Current Food and Drug Administration (FDA)-approved levels of adequacy and of upper limits in infant formulas for vitamin A are 250 and 750 IU per 100 kcal, respectively. The level of adequacy is generous relative to need. Because vitamin A toxicity has been noted in infants at intakes of 2,100 IU per 100 kcal, an upper limit might well be selected in the range of 750-1,000 IU per 100 kcal for healthy infants. Some children and adults, however, are intolerant of relatively low intakes. The current FDA-approved adequacy level for vitamin K is 4 micrograms per 100 kcal, which also is generous relative to need. An upper limit has not previously been set. Neither single intramuscular doses of phylloquinone that are 100 times the RDA (RDI) for infants nor diets that contain 10-20 times the RDA (RDI) for adults show any adverse effects. Some allergic reactions to injected vitamin K have been reported, however, and menadione, even in low doses, shows significant toxicity in neonates. Thus, although toxicity to phylloquinone is unlikely, it has been suggested that the upper limit of phylloquinone in infant formulas be set at 20 micrograms per 100 kcal, primarily to discourage nutritionally unwarranted supplementation.