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Concept: Vitamin K


Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.

Concepts: Immune system, Coagulation, Escherichia coli, Folic acid, Coeliac disease, Vitamin K, Malabsorption, Methylenetetrahydrofolate reductase


We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology.METHODS AND RESULTS: The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%).CONCLUSION: The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

Concepts: Atrial fibrillation, Warfarin, Standard deviation, Anticoagulant, Amiodarone, Cardioversion, Vitamin K, Flecainide


To the Editor: In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), investigators found that rivaroxaban was noninferior to warfarin in the prevention of stroke and systemic embolism in patients with atrial fibrillation.(1) In December 2014, four years after completion of the trial, the Food and Drug Administration (FDA) issued a recall notice for a medical device correction of the Alere INRatio Monitor System (formally known as the Hemosense INRatio device). The recall correction notice was issued because the FDA-approved and European . . .

Concepts: Stroke, Atrial fibrillation, Coagulation, Warfarin, Thrombus, Anticoagulant, Vitamin K, Embolism


The purpose of this review is to examine vitamin D in the context of sport nutrition and its potential role in optimizing athletic performance. Vitamin D receptors (VDR) and vitamin D response elements (VDREs) are located in almost every tissue within the human body including skeletal muscle. The hormonally-active form of vitamin D, 1,25-dihydroxyvitamin D, has been shown to play critical roles in the human body and regulates over 900 gene variants. Based on the literature presented, it is plausible that vitamin D levels above the normal reference range (up to 100 nmol/L) might increase skeletal muscle function, decrease recovery time from training, increase both force and power production, and increase testosterone production, each of which could potentiate athletic performance. Therefore, maintaining higher levels of vitamin D could prove beneficial for athletic performance. Despite this situation, large portions of athletic populations are vitamin D deficient. Currently, the research is inconclusive with regards to the optimal intake of vitamin D, the specific forms of vitamin D one should ingest, and the distinct nutrient-nutrient interactions of vitamin D with vitamin K that affect arterial calcification and hypervitaminosis. Furthermore, it is possible that dosages exceeding the recommendations for vitamin D (i.e. dosages up to 4000-5000 IU/day), in combination with 50 to 1000 mcg/day of vitamin K1 and K2 could aid athletic performance. This review will investigate these topics, and specifically their relevance to athletic performance.

Concepts: Cholesterol, Osteoporosis, Vitamin D, Critical thinking, Vitamin, Vitamins, Human body, Vitamin K


The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial.

Concepts: Diabetes mellitus, Stroke, Atrial fibrillation, Coagulation, Warfarin, Thrombus, Anticoagulant, Vitamin K


Vitamin K has important functions within the body, some of which are still being discovered. Research has shown that vitamin K is an anticalcification, anticancer, bone-forming and insulin-sensitising molecule. Recent data indicate that subclinical vitamin K deficiency is not uncommon. Additionally, vitamin K antagonists such as warfarin may cause detrimental side effects, which may partly be blunted through vitamin K supplementation.

Concepts: Osteoporosis, Warfarin, Protein C, Vitamin K, Factor X, Protein Z, Coumarin, Vitamin K epoxide reductase


Oral anticoagulant options have exploded. Dabigatran, a direct thrombin inhibitor, was approved for use in the United States in 2010 for the prevention of stroke in patients with atrial fibrillation; this was rapidly followed by approval of the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban within 5 years. The drive for the development of these drugs stemmed from the burdens associated with the use of the anticoagulants that had previously been available for outpatient treatment - subcutaneous heparins and oral vitamin K antagonists. Although these new drugs represent an important advance in anticoagulation therapy, concern over the lack of . . .

Concepts: Atrial fibrillation, Warfarin, Anticoagulant, Heparin, Dabigatran, Anticoagulants, Vitamin K, Direct thrombin inhibitor


Teriparatide (PTH1-34) promotes skeletal repair and increases bone mass. Vitamin K is involved in bone mineralization as a coenzyme of γ-carboxylase for Gla proteins, and therefore vitamin K insufficiency caused by malnutrition or therapeutic intake of the vitamin K antagonist warfarin could affect the efficacy of PTH1-34 therapy for bone repair. In the present study, we investigated whether vitamin K influences the efficacy of PTH1-34 therapy for bone repair in a rat osteotomy model. Female 12-week-old Sprague-Dawley rats were subjected to a closed midshaft osteotomy of the femur and randomized into four groups (n=10 per group): Vehicle, PTH1-34 (daily 30μg/kg/day subcutaneous injection)+solvent (orally, three times a week), PTH1-34+warfarin (0.4mg/kg/day orally, three times a week), and PTH1-34+vitamin K2 (menatetrenone, 30mg/kg/day orally, three times a week). Serum γ-carboxylated and uncarboxylated osteocalcin (Gla-OC and Glu-OC) levels and radiographic healing were monitored every 2weeks. Skeletal repair was assessed by micro-computed tomography, mechanical testing, and histology at 8weeks after the surgery. PTH1-34 amplified the osteotomy-induced increase in Gla-OC and improved the mechanical properties as well as the volumetric bone mineral tissue density of the fracture callus. Concurrent use of warfarin decreased the response to PTH1-34 therapy in terms of mechanical recovery, probably by impairing mineralization due to the lack of Gla-OC. Although the effects of combination therapy with PTH1-34 and vitamin K2 on bone repair did not significantly exceed those of PTH1-34 monotherapy in rats fed sufficient dietary vitamin K, postoperative Gla-OC levels were correlated with the mechanical properties of the osteotomized femur in PTH1-34-treated rats regardless of the use of warfarin or vitamin K2. These findings suggest the importance of vitamin K dependent γ-carboxylation of OC for realizing the full effects of PTH1-34 on skeletal repair.

Concepts: Osteoporosis, Skeletal system, Warfarin, Affect, Vitamin K, Coumarin, Carboxylation, Vitamin K epoxide reductase


There is an almost unanimous consensus on the management of the direct new oral anticoagulants, dabigatran, rivaroxaban, and apixaban in elective surgery. However, this general consensus does not exist in relation with the direct new oral anticoagulants use in emergency surgery, especially in the bleeding patient. For this reason, a literature review was performed using the MEDLINE-PubMed. An analysis was made of the journal articles, reviews, systematic reviews, and practices guidelines published between 2000 and 2014 using the terms “monitoring” and “reversal”. From this review, it was shown that the routine tests of blood coagulation, such as the prothrombin time and activated partial thromboplastin time, have a limited efficacy in the perioperative control of blood coagulation in these patients. There is currently no antidote to reverse the effects of these drugs, although the possibility of using concentrated prothrombin complex and recombinant activated factor vii has been suggested for the urgent reversal of the anticoagulant effect.

Concepts: Coagulation, Warfarin, Anticoagulant, Heparin, Blood transfusion, Prothrombin time, Vitamin K, Direct thrombin inhibitor


The new oral anticoagulants have many advantages over vitamin K antagonists, but they are still associated with a troublesome incidence of major bleeding. Additionally, the absence of a reversal agent for the new oral anticoagulants is a barrier to their more widespread use. Currently, there are 3 potential reversal agents in development: idarucizumab is a humanized murine monoclonal antibody fragment directed specifically at dabigatran; andexanet alfa is a recombinant modified decoy factor Xa that binds to factor Xa inhibitors; and PER977 is a small molecule that binds to factor Xa and IIa inhibitors and to heparin-based anticoagulants through charge interaction. These agents have undergone phase I clinical testing, appear to be well tolerated in healthy volunteers, and are effective in neutralizing their respective targets. All 3 are currently undergoing or entering into a phase II or III clinical study. This article reviews the available data for idarucizumab, andexanet alfa, and PER977.

Concepts: Epidemiology, Clinical trial, Monoclonal antibodies, Warfarin, Anticoagulant, Dabigatran, Vitamin K, Factor X