Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin

Crowther, Mark; Ageno, Walter; García, David; Wang, Luqi; Witt, Dan M.; Clark, Nathan P.; Blostein, Mark; Kahn, Susan R.; Vesely, Sara K.; Schulman, Sam; Kovacs, Michael J.; Rodger, Marc; Wells, Phillip S.; Anderson, David R.; Ginsberg, J. S.; Selby, Rita; Siragusa, Sergio; Silingardi, Mauro; Dowd, Mary Beth; Kearon, Clive

doi:10.7326/0003-4819-150-5-200903030-00005

Cited by 139 publications

(77 citation statements)

References 25 publications

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“…These generalizations are consistent with recent findings by Crowther et al 27 The VKORC1 (VKOR complex, subunit 1) gene located on chromosome 16 at band p11.2 encodes the VKOR enzyme, a small transmembrane protein of the endoplasmic reticulum. Transcription of VKORC1 occurs primarily in the liver; however, smaller amounts of VKORC1 are present in the heart and pancreas.…”

Section: Incidence Of Warfarin-related Adessupporting

confidence: 81%

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Moyer

O’Kane

Baudhuin

et al. 2009

Mayo Clinic Proceedings

112

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ADE = adverse drug event; AEI = American Enterprise Institute; ASPE = allele-specific primer extension; CYP2C9 = cytochrome P450 2C9; INR = international normalized ratio; PCR = polymerase chain reaction; SNP = single-nucleotide polymorphism; VitKH 2 = vitamin K hydroquinone; VKOR = vitamin K epoxide reductase; VKORC1 = VKOR complex, subunit 1 W arfarin is a well-accepted therapy used for the prevention of stroke in patients with atrial fibrillation, for prophylaxis of venous thromboembolism and pulmonary embolism in patients with prosthetic heart valves and myocardial infarction, and for prevention of pulmonary embolism or deep venous thrombosis in patients undergoing orthopedic surgery or with a history of venous or arterial thromboembolism. Many reviews and clinical practice guidelines (summarized by Ansell et al, 1 Baglin et al, 2 Flockhart et al, 3 Husted et al, 4 and Singer et al 5 ) outline the substantial benefits of warfarin therapy for the prevention of strokes in these patients. The American Enterprise Institute (AEI)-Brookings Joint Center for Regulatory Studies Report, which reviewed the use of warfarin in the United States, estimates that approximately 2 million US citizens are prescribed warfarin annually. 6 In 2003, a total of 21.2 million prescriptions were written for oral warfarin in the United States. 7 Warfarin interferes with coagulation by inhibiting regeneration of the reduced form of vitamin K, a cofactor in the γ-glutamyl-carboxylase -mediated activation of coagulation factors II, VII, IX, and X ( Figure 1). The oxidized, inactive form of vitamin K is converted to the reduced form of vitamin K by vitamin K epoxide reductase (VKOR); warfarin inhibits VKOR, resulting in less of the reduced form of vitamin K available to support the factor carboxylation required to sustain the coagulation cascade. 8 Warfarin has a narrow therapeutic index that contributes either to therapeutic failure (potentially leading to stroke or other complications) or therapeutic excess (potentially leading to bleeding and hemorrhage). Many surveys have described the incidence of warfarin-related adverse drugThe antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to ach...

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Section: Incidence Of Warfarin-related Adessupporting

confidence: 81%

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Moyer

O’Kane

Baudhuin

et al. 2009

Mayo Clinic Proceedings

112

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“…The patients' educational process has began a new era in which educational results should take into account the level of patients' literacy, barriers to learning and cost-effectiveness relationships, giving priority to educational content and using validated instruments to measure the results of instruction provided (25) . It is necessary to recognize that the assisted individuals develop, due to their experiences, a certain understanding of procedures and recommendations defended by the health services and, consequently, certain attitudes in relation to them.…”

Section: Discussionmentioning

confidence: 99%

Knowledge of Patients with Mechanical Valve Prostheses Concerning Chronic Oral Anticoagulant Therapy

Rocha¹,

Rabelo

Aliti

et al. 2010

Rev. Latino-Am. Enfermagem

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Adherence to chronic Oral Anticoagulant Therapy (OAT) is directly related to patients' understanding of the therapy. This study verified the knowledge of patients with mechanical valve prostheses concerning OAT. This is a contemporary cross-sectional study, the sample is composed of patients with mechanical valve prostheses (MVP) in outpatient follow-up.A 10-question instrument was used; answers were 'know' (1 point), 'know partially' (half point), or 'do not know' (zero). Patients were grouped according to the result obtained: ≤ 4 points was considered insufficient knowledge; > 4 ≤ 8 equated to moderate knowledge; and > 8 was considered appropriate knowledge. Of the 110 patients, 61.8% presented moderate knowledge, 40.9% were not able to name at least one factor that may alter the INR (International Normalized Ratio) and 37.3% were not able to report their INR target range. The majority of patients presented moderate knowledge concerning the treatment.Strategies to improve knowledge on the topic should be implemented to minimize risks. Conocimiento de los pacientes portadores de prótesis valvular mecánica sobre la terapia de anticoagulación oral crónicaEl objetivo de este estudio fue verificar el conocimiento de pacientes con prótesis valvular sobre la terapia de anticoagulación oral. La adhesión a la terapia de anticoagulación oral crónica está directamente relacionada al entendimiento del paciente sobre esta terapia.Se trata de un estudio transversal contemporáneo, en el cual se incluyeron pacientes de ambulatorio con prótesis valvular mecánica (PVM). Se aplicó un cuestionario con 10 preguntas; las respuestas fueron "sabe" (1 punto), "sabe parcialmente" (medio punto), "no sabe" (cero puntos). Los pacientes fueron agrupados según la puntuación obtenida: ≤ 4 puntos, conocimiento insuficiente; > 4 ≤ 8 puntos, conocimiento regular; > 8 puntos, conocimiento adecuado. De los 110 pacientes incluidos, el 61,8% demostró conocimiento regular, 40,9% no supieron citar un factor que altera el REI (razón estandarizada internacional) y 37,3% no supieron informar su REI objetivo. Se concluyó que la mayoría de los pacientes demostró conocimiento regular sobre el tratamiento. Se recomienda implantar estrategias para mejorar el conocimiento y minimizar los riesgos de la terapia.

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“…This was addressed in a recent study by Crowther et al who randomized 702 asymptomatic patients with an INR between 4.5 and 10-1.25 mg oral vitamin K or placebo with a follow up of 90 days to establish the impact on bleeding events and thromboembolism [53]. Sixty-two percent of the patients had at least 1 risk factor for bleeding (35% had a previous bleeding event, 17% had a malignancy and 10% renal impairment).…”

Section: Influence Of Vitamin K On Bleeding and Thrombosismentioning

confidence: 93%

Warfarin anticoagulation reversal: management of the asymptomatic and bleeding patient

Makris

Veen

Maclean

2009

J Thromb Thrombolysis

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The management of patients with supra-therapeutic INR in a common clinical problem. The risk of bleeding is influenced by the intensity, variability and duration of anticoagulation, patient age, presence of co-morbidities and concomitant drug therapy. For the asymptomatic patient, warfarin discontinuation is all that is usually required but for individuals at high risk of bleeding and those with INR > 10, oral vitamin K administration is recommended. In the presence of major bleeding, treatment with intravenous vitamin K and prothrombin complex concentrate is the most effective therapy.

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Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin

Abstract: Canadian Institutes of Health Research and Italian Ministry of Universities and Research.

Cited by 139 publications

References 25 publications

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Knowledge of Patients with Mechanical Valve Prostheses Concerning Chronic Oral Anticoagulant Therapy

Warfarin anticoagulation reversal: management of the asymptomatic and bleeding patient

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