Treatment of excessive anticoagulation with phytonadione (vitamin K): A meta-analysis

William Beaumont Army Medical Center, El Paso, Tex. 79920-5001, USA.
Archives of Internal Medicine (Impact Factor: 17.33). 03/2006; 166(4):391-7. DOI: 10.1001/.391
Source: PubMed


Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a meta-analysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation.
The MEDLINE, EMBASE, and Cochrane Library databases were searched (without language restrictions) for articles published between January 1985 and September 2004. Randomized controlled trials or prospective, nonrandomized trials that used vitamin K to treat patients without major hemorrhage with an INR greater than 4.0 due to oral anticoagulant use were included. The primary outcome was achievement of the target INR (1.8-4.0) at 24 hours after vitamin K administration. Summary estimates were calculated using a random effects model.
Twenty-one studies (10 randomized and 11 prospective trials) were included. Among oral vitamin K treatment arms (4, n = 75), the proportion with a target INR at 24 hours was 82% (95% confidence interval [CI], 70%-93%), which was similar to intravenous vitamin K treatment arms (6, n = 69; target INR, 77%; 95% CI, 60%-95%). Treatment arms of subcutaneous vitamin K (3, n = 58; 31%; 95% CI, 7%-55%) and placebo/observation (2, n = 27; 20%; 95% CI, 0%-47%) were less likely to achieve target INR at 24 hours. Only 1 of 21 trials appropriately assessed for adverse events, so a summary estimate for bleeding risk could not be generated.
Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.

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Available from: Patrick G O'Malley, Dec 04, 2014
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    • "The recommended indications for usage of vitamin K for supratherapeutic INR with no major bleeding are described in the Table 3. Vitamin K can be administered orally and intravenously [50]. For non-bleeding patients with INR >4 oral vitamin K at doses between 1 and 2.5 mg will lower INR within 24 hours [51]. Despite the advantage of rapid lowering of INR with intravenous vitamin K compared to oral, similar degrees of INR correction have been noted at 24 hours [52]. "
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    ABSTRACT: The prescription of new oral anticoagulants is on the rise. As opposed to vitamin K antagonists and heparins the new agents have single targets in the coagulation cascade, more predictable pharmacokinetics and they lack validated and available antidotes. In general, the new agents have similar or lower bleeding risk than vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for bleeding are typically the same for old and new anticoagulants. Old age, renal dysfunction and concomitant antiplatelet agents seem to be recurring risk factors. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. With the exception of vitamin K (for vitamin K antagonists) and protamine (for heparin) the same array of prohemostatic agents - unactivated or activated prothrombin complex concentrate, and activated factor VIIa - have been tried for almost all anticocoagulants in different models, and for some agents also in patients, with varying success. Hemodialysis can reduce the level of dabigatran efficiently and activated charcoal may be used for very recent oral ingestion of lipophilic agents. In view of the shorter half life of the new agents compared to warfarin the need for reversal agents may be less critical. Nevertheless, highly specific reversal agents for the thrombin- and factor Xa-inhibitors are under development and might be available within two years. © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 05/2014; 133 Suppl 2(Suppl 2):S158-66. DOI:10.1016/S0049-3848(14)50026-6 · 2.45 Impact Factor
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    • "This may have prevented some of the delays in surgery in this study e.g. warfarin cessation and INR reduction [17, 18]. We would concur with British Orthopaedic Association guidelines suggesting these fractures are best managed by a full time consultant or staff grade physician on a fracture ward, providing daily medical care and advice in the perioperative management of older patients with hip fractures [19]. "
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    Journal of Orthopaedics and Traumatology 07/2013; 15(1). DOI:10.1007/s10195-013-0248-9
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    • "Vitamin K can be administered subcutaneously, orally, or intravenously. Subcutaneous vitamin K is not significantly different from placebo in terms of correcting aberrant INRs.27 Although both oral and intravenously administered vitamin K are effective at correcting supratherapeutic INRs at 24 hours posttreatment, intravenous vitamin K can correct the INR much sooner, in as few as 4 to 6 hours.5,28 "
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    ABSTRACT: Warfarin, an oral vitamin K antagonist, is used to prevent arterial and venous thromboembolism in patients suffering from a multitude of diseases. In 2004, 31 million warfarin prescriptions were dispensed in the United States. Warfarin inhibits the activation of the vitamin K-dependent clotting factors (Factors II, VII, IX, and X) and regulatory proteins (proteins C, S, and Z). It is one of the leading drugs implicated in emergency room visits for adverse drug reactions. Annually the frequency of bleeding complications associated with overanticoagulation is 15% to 20%, with fatal bleeds measuring as high as 1% to 3%. The most effective method of warfarin reversal involves the use of Four Factor Prothrombin Complex Concentrate (PCC), which is widely used throughout Europe but is unavailable in the United States. The current therapies available to emergency room physicians in the United States are fresh frozen plasma, recombinant Factor VIIa (rFVIIa), Factor Eight Inhibitory Bypassing Activity, or Three Factor PCC concomitantly administered with vitamin K. We review the advantages and disadvantages of these therapies and recommend Three Factor PCC with small doses of rFVIIa and with vitamin K in life-threatening situations if Four Factor PCC is unavailable.
    The western journal of emergency medicine 11/2011; 12(4):386-92. DOI:10.5811/westjem.2011.3.2051
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