• coronary artery disease
• menaquinone-4
• menaquinone-7
• vitamin K2

• Diabetes
• Medial arterial calcification
• Peripheral arterial disease

• Humans
• Diabetic Angiopathies/epidemiology
• Diabetic Angiopathies/physiopathology
• Peripheral Arterial Disease/epidemiology
• Peripheral Arterial Disease/physiopathology
• Lower Extremity/blood supply
• Lower Extremity/pathology
• Vascular Calcification/epidemiology

• cardiovascular disease
• cohort study
• diabetic
• nephropathy
• type 1 diabetes

• Humans
• Diabetes Mellitus, Type 1/complications
• Diabetes Mellitus, Type 1/blood
• Diabetes Mellitus, Type 1/mortality
• Male
• Female
• Kidney Failure, Chronic/blood
• Kidney Failure, Chronic/mortality
• Kidney Failure, Chronic/complications
• Vitamin K Deficiency/blood
• Vitamin K Deficiency/complications
• Middle Aged
• Cardiovascular Diseases/mortality
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/blood
• Cardiovascular Diseases/epidemiology
• Adult
• Diabetic Nephropathies/mortality
• Diabetic Nephropathies/blood
• Vitamin K/blood
• Matrix Gla Protein
• Extracellular Matrix Proteins/blood
• Calcium-Binding Proteins/blood
• Proportional Hazards Models
• Disease Progression
• Cause of Death
• Cohort Studies
• Risk Factors

• NNF19OC0058130 Novo Nordisk Fonden
• Novo Nordisk Fonden

• Vitamin K2
• application
• biological production
• fermentation
• metabolic pathways

• Bacillus natto
• Fermentation
• Menaquinone-7
• Precursors
• Vitamin K2

• Humans
• Vitamin K 2/metabolism
• Shikimic Acid/metabolism
• Sodium Glutamate/metabolism
• Fermentation
• Bacillus subtilis/genetics
• Pyruvates/metabolism

• 2022 Jiangsu Province "333" project
• No. 2019YFA0905700 National Key Research and Development Program of China
• No. 21878151 National Natural Science Foundation of China
• XTD2213 Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture
• BK20211535 Natural Science Foundation of Jiangsu Province

• Atherosclerosis
• Computed tomography
• Intracranial carotid artery
• Medial calcification
• Risk factors

• Humans
• Male
• Female
• Middle Aged
• Adult
• Carotid Artery, Internal/diagnostic imaging
• Aged
• Carotid Artery Diseases/diagnostic imaging
• Carotid Artery Diseases/epidemiology
• Vascular Calcification/diagnostic imaging
• Vascular Calcification/epidemiology
• Sex Factors
• Young Adult
• Risk Assessment
• Risk Factors
• Tunica Intima/diagnostic imaging
• Tunica Intima/pathology
• Computed Tomography Angiography
• Tunica Media/diagnostic imaging
• Tunica Media/pathology
• Heart Disease Risk Factors

• chronic kidney disease
• diabetes mellitus
• vascular calcification

• National Natural Science Foundation of China (82070455); the related Foundation of Jiangsu Province (BK20201225, BE2022780)

• cancer
• fat-soluble vitamin
• matrix metalloproteinases

• Humans
• Vitamin A/pharmacology
• Matrix Metalloproteinase 2
• Vitamins/therapeutic use
• Vitamin K
• Cardiovascular Diseases/drug therapy
• Vitamin D/therapeutic use
• Vitamin E

• 2022R1F1A1074609 National Research Foundation of Korea

• Bacillus subtilis
• Scanning electron microscope
• Surfactants
• Synthetic pathway
• qRT-PCR

• 31871781 National Nature Science Foundation of China
• 31772081 National Nature Science Foundation of China

• bacterial cell immobilisation
• biological significance
• fermentation
• iron oxide nanoparticles
• menaquinone-7 isomers

• Humans
• Warfarin/pharmacology
• Vitamin K Epoxide Reductases/chemistry
• Anticoagulants/pharmacology
• Metabolism, Inborn Errors

• R01 AI158500 NIAID NIH HHS
• R24 GM136766 NIGMS NIH HHS
• R01 HL121718 NHLBI NIH HHS
• R01 GM131008 NIGMS NIH HHS
• P41 GM103422 NIGMS NIH HHS

• Rats
• Animals
• Vitamin K 2/pharmacology
• Vitamin K 2/metabolism
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha/metabolism
• Interleukin-6/metabolism
• Oxidative Stress
• Myocardial Reperfusion Injury/pathology
• Superoxide Dismutase/metabolism
• Glutathione
• Myocardium/pathology

• aorta, abdominal
• flavonoids
• observational study
• tea
• vascular calcification
• vascular diseases

• Bioactivity
• Fermentation
• Media optimisation
• Menaquinone-7 isomers

• Fermentation
• Glucose
• Vitamin K 2/analogs & derivatives
• Vitamins

• University of Waikato

• Coronary artery calcification
• Coronary heart disease
• Vitamin K

• Aged
• Coronary Artery Disease
• Humans
• Middle Aged
• Retrospective Studies
• Vascular Calcification
• Vitamin K
• Vitamin K 1

• kidney function
• kidney transplant
• matrix Gla protein
• osteocalcin
• vascular calcification
• vitamin K

• Biological Specimen Banks
• Biomarkers/blood
• Cohort Studies
• Cross-Sectional Studies
• Female
• Humans
• Kidney/physiopathology
• Kidney Transplantation
• Luminescent Measurements
• Male
• Middle Aged
• Netherlands
• Postoperative Complications/blood
• Postoperative Complications/physiopathology
• Prospective Studies
• Vitamin K/blood
• Vitamin K Deficiency/blood
• Vitamin K Deficiency/physiopathology

• A1003 Astellas Pharma, Netherlands

Preinjury anticoagulation therapy (AT) is associated with a higher risk for major bleeding. We aimed to evaluated the influence of preinjury anticoagulant medication on the clinical course after moderate and severe trauma. Patients in the TraumaRegister DGU ≥ 55 years who received AT were matched with patients not receiving AT. Pairs were grouped according to the drug used: Antiplatelet drugs (APD), vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). The primary end points were early (< 24 h) and total in-hospital mortality. Secondary endpoints included emergency surgical procedure rates and surgery rates. The APD group matched 1759 pairs, the VKA group 677 pairs, and the DOAC group 437 pairs. Surgery rates were statistically significant higher in the AT groups compared to controls (APD group: 51.8% vs. 47.8%, p = 0.015; VKA group: 52.4% vs. 44.8%, p = 0.005; DOAC group: 52.6% vs. 41.0%, p = 0.001). Patients on VKA had higher total in-hospital mortality (23.9% vs. 19.5%, p = 0.026), whereas APD patients showed a significantly higher early mortality compared to controls (5.3% vs. 3.5%, p = 0.011). Standard operating procedures should be developed to avoid lethal under-triage. Further studies should focus on detailed information about complications, secondary surgical procedures and preventable risk factors in relation to mortality.

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries.

Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy.

Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51–4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53–2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36–13.56, P = 0.0018).

Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

• calcification
• carotid artery
• computed tomography angiography
• histology
• vascular calcification
• warfarin

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

• calcium paradox
• menaquinone
• osteoporosis
• vascular calcification
• vitamin K2

• ER stress
• FGF21
• FGF23
• congestive heart failure
• hydrogen sulfide
• marinobufagenin
• nitric oxide
• nutraceuticals
• plant-based diets
• ventricular hypertrophy

• Acetylcysteine/pharmacology
• Animals
• Antioxidants/pharmacology
• Diet
• Dietary Supplements
• Endoplasmic Reticulum Stress
• Exercise
• Fibroblast Growth Factor-23
• Functional Food
• Heart Failure/drug therapy
• Heart Failure/prevention & control
• Humans
• Hypertrophy, Left Ventricular/drug therapy
• Hypertrophy, Left Ventricular/prevention & control
• Life Style
• Nitric Oxide/metabolism
• Oxidative Stress/drug effects

• Cardiovascular disease
• Chronic kidney disease
• Vascular calcification

Warfarin, a vitamin K antagonist (VKA), is known to promote arterial calcification (AC). In the present study, we conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA); 6655 participants were included. From MESA data, we found that AC was related to both age and vitamin K; furthermore, the score of AC increased with SASP marker including interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) rising. Next, a total of 79 warfarin users in our center developed significantly more calcified coronary plaques as compared to non-VKA users. We investigated the role of warfarin in phosphate-induced AC in different ages by in vitro experimental study. Furthermore, dose-time-response of warfarin was positively correlated with AC score distribution and plasma levels of the SASP maker IL-6 among patients < 65 years, but not among patients ≥ 65 years. In addition, in vitro research suggested that warfarin treatment tended to deteriorate calcification in young VSMC at the early stage of calcification. Our results suggested that aging and warfarin-treatment were independently related to increased AC. Younger patients were more sensitive to warfarin-related AC than older patients, which was possibly due to accumulated warfarin-induced cellular senescence.

Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.

• aging
• cigarette smoke
• endothelial dysfunction
• menaquinone
• mitochondrial dysfunction
• oxidative stress
• ubiquinol
• vitamin K

Type 2 diabetes mellitus is a chronic disease that is characterized by hyperglycemia, insulin resistance, and dysfunctional insulin secretion. Glycemic control remains a crucial contributor to the progression of type 2 diabetes mellitus as well as the prevention or delay in the onset of diabetes-related complications. Vitamin K is a fat-soluble vitamin that plays an important role in the regulation of the glycemic status. Supplementation of vitamin K may reduce the risk of diabetes mellitus and improve insulin sensitivity. This mini-review summarizes the recent insights into the beneficial effects of vitamin K and its possible mechanism of action on insulin sensitivity and glycemic status, thereby suppressing the progression of diabetes mellitus.

• diabetes mellitus
• glycemic status
• insulin sensitivity
• vitamin K

• Adult
• Aged
• Diabetes Complications/prevention & control
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/prevention & control
• Dietary Supplements
• Disease Progression
• Female
• Glycemic Control
• Humans
• Insulin Resistance
• Male
• Middle Aged
• Nutritional Status
• Vitamin K/administration & dosage
• Vitamin K/pharmacology
• Vitamin K/physiology
• Young Adult

• Chronic Kidney Disease
• Kidney
• Vascular

• 1
• 4-dihydroxy-2-naphthoic acid (DHNA)
• Bacillus subtilis natto
• DHNA prenyltransferase (MenA)
• Menaquinone
• Site-directed mutagenesis

• cardiac epidemiology
• coronary heart disease
• nutrition & dietetics

• Adult
• Cohort Studies
• Coronary Disease/epidemiology
• Diet
• Female
• Humans
• Male
• Middle Aged
• Norway/epidemiology
• Prospective Studies
• Risk Factors
• Vitamin K

• PIVKA-II
• Vitamin K
• coagulation
• hip fracture
• phylloquinone

• CAC, coronary artery calcification
• CI, confidence interval
• CKD, chronic kidney disease
• CT, computed tomography
• CV, cardiovascular
• CVD, cardiovascular disease
• ESKD, end-stage kidney disease
• FGF, fibroblast growth factor
• HR, hazard ratio
• LDL-C, low-density lipoprotein cholesterol
• MGP, matrix Gla protein
• PTH, parathyroid hormone
• VSMC, vascular smooth muscle cell
• chronic kidney disease
• dialysis
• eGFR, estimated glomerular filtration rate
• medial calcification
• vascular calcification

Cerebral ischemia/reperfusion (I/R) injury causes cognitive deficits, excitotoxicity, neuroinflammation, oxidative stress and brain edema. Vitamin K2 (Menaquinone 4, MK-4) as a potent antioxidant can be a good candidate to ameliorate I/R consequences. This study focused on the neuroprotective effects of MK-4 for cerebral I/R insult in rat’s hippocampus. The rat model of cerebral I/R was generated by transient bilateral common carotid artery occlusion for 20 min. Rats were divided into control, I/R, I/R+DMSO (solvent (1% v/v)) and I/R+MK-4 treated (400 mg/kg, i.p.) groups. Twenty-four hours after I/R injury induction, total brain water content, superoxide dismutase (SOD) activity, nitrate/nitrite concentration and neuronal density were evaluated. In addition to quantify the apoptosis processes, TUNEL staining, as well as expression level of Bax and Bcl2, were assessed. To evaluate astrogliosis and induced neurotoxicity by I/R GFAP and GLT-1 mRNA expression level were quantified. Furthermore, pro-inflammatory cytokines including IL-1β, IL-6 and TNF-α were measured. Seven days post I/R, behavioral analysis to quantify cognitive function, as well as Nissl staining for surviving neuronal evaluation, were conducted. The findings indicated that administration of MK-4 following I/R injury improved anxiety-like behavior, short term and spatial learning and memory impairment induced by I/R. Also, MK-4 was able to diminish the increased total brain water content, apoptotic cell density, Bax/ Bcl2 ratio and GFAP mRNA expression following I/R. In addition, the high level of nitrate/nitrite, IL-6, IL-1β and TNF-α induced by I/R was reduced after MK-4 administration. However, MK-4 promotes the level of SOD activity and GLT-1 mRNA expression in I/R rat model. The findings demonstrated that MK-4 can rescue transient global cerebral I/R consequences via its anti-inflammatory and anti-oxidative stress features. MK-4 administration ameliorates neuroinflammation, neurotoxicity and neuronal cell death processes and leads to neuroprotection.

• Animals
• Apoptosis
• Brain/drug effects
• Brain/metabolism
• Brain Ischemia/drug therapy
• Excitatory Amino Acid Transporter 2/genetics
• Excitatory Amino Acid Transporter 2/metabolism
• Glial Fibrillary Acidic Protein/genetics
• Glial Fibrillary Acidic Protein/metabolism
• Interleukin-1beta/genetics
• Interleukin-1beta/metabolism
• Interleukin-6/genetics
• Interleukin-6/metabolism
• Male
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/therapeutic use
• Rats
• Rats, Wistar
• Reperfusion Injury/drug therapy
• Spatial Learning
• Superoxide Dismutase/genetics
• Superoxide Dismutase/metabolism
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism
• Vitamin K 2/analogs & derivatives
• Vitamin K 2/pharmacology
• Vitamin K 2/therapeutic use

• Ferdowsi University of Mashhad

• macroangiopathy
• microangiopathy
• vitamins

• Diabetes Mellitus, Type 2
• Diabetic Angiopathies/epidemiology
• Humans
• Vascular Diseases
• Vitamin K 1
• Vitamins

• KEJ Fond, Copenhagen, Denmark
• Department of Regional Health Research, The Faculty of Health Science, The University of Southern Denmark (SDU), Denmark
• Region of Southern Denmark, Denmark

Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the production of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-κB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-κB signaling in both in vitro and in vivo studies, suggesting that vitamin K may prevent vascular calcification via anti-inflammatory mechanisms. Matrix Gla protein (MGP) is a major inhibitor of soft tissue calcification and contributes to preventing both intimal and medial vascular calcification. Vitamin K may also inhibit progression of vascular calcification by enhancing the activity of MGP through facilitating its γ-carboxylation. In support of this hypothesis, the procalcific effects of warfarin, an antagonist of vitamin K, on arterial calcification have been demonstrated in several clinical studies. Among the inactive MGP forms, dephospho-uncarboxylated MGP (dp-ucMGP) may be regarded as the most useful biomarker of not only vitamin K deficiency, but also vascular calcification and CVD. There have been several studies showing the association of circulating levels of dp-ucMGP with vitamin K intake, vascular calcification, mortality, and CVD. However, additional larger prospective studies including randomized controlled trials are necessary to confirm the beneficial effects of vitamin K supplementation on CV health.

• atherosclerosis
• matrix Gla protein
• oncostatin M
• vascular calcification

• Animals
• Biomarkers/blood
• Cardiovascular Diseases/blood
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/mortality
• Cardiovascular Diseases/pathology
• Disease Progression
• Humans
• Inflammation/blood
• Inflammation/drug therapy
• Inflammation/pathology
• Vascular Calcification/blood
• Vascular Calcification/drug therapy
• Vitamin K/therapeutic use

• matrix Gla protein
• vascular calcification
• vitamin K

• Calcification inducer
• Calcification inhibitor
• Fibroblast growth factor 21
• Smooth muscle phenotypic switch
• Vascular calcification

• Bacillus
• Downstream processing
• Menaquinone
• Process engineering
• Strain improvement
• Vitamin K2

• atherosclerosis
• malnutrition
• peripheral arterial disease

• Diet, Healthy
• Humans
• Malnutrition/diagnosis
• Malnutrition/epidemiology
• Malnutrition/physiopathology
• Malnutrition/therapy
• Nutrition Therapy/methods
• Nutritional Status
• Nutritive Value
• Peripheral Arterial Disease/diagnosis
• Peripheral Arterial Disease/epidemiology
• Peripheral Arterial Disease/physiopathology
• Peripheral Arterial Disease/therapy
• Protective Factors
• Recommended Dietary Allowances
• Risk Assessment
• Risk Factors
• Risk Reduction Behavior
• Treatment Outcome

• Ectopic mineralization
• Keutel syndrome
• PXE-like syndrome
• chronic kidney disease
• matrix gla protein
• pseudoxanthoma elasticum
• vascular calcification
• vitamin K

• Abnormalities, Multiple
• Animals
• Calcinosis/genetics
• Calcinosis/metabolism
• Cartilage Diseases
• Genetic Diseases, Inborn/genetics
• Genetic Diseases, Inborn/metabolism
• Hand Deformities, Congenital
• Humans
• Pulmonary Valve Stenosis
• Vitamin K/genetics
• Vitamin K/metabolism

• BOF08/01M01108 Universiteit Gent

Atherosclerosis is a chronic low-grade inflammatory disease that affects large and medium-sized arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). The high risk of mortality by atherosclerosis has led to the development of new strategies for disease prevention and management, including immunonutrition. Plant-based dietary patterns, functional foods, dietary supplements, and bioactive compounds such as the Mediterranean Diet, berries, polyunsaturated fatty acids, ω-3 and ω-6, vitamins E, A, C, and D, coenzyme Q10, as well as phytochemicals including isoflavones, stilbenes, and sterols have been associated with improvement in atheroma plaque at an inflammatory level. However, many of these correlations have been obtained in vitro and in experimental animals' models. On one hand, the present review focuses on the evidence obtained from epidemiological, dietary intervention and supplementation studies in humans supporting the role of immunonutrient supplementation and its effect on anti-inflammatory response in atherosclerotic disease. On the other hand, this review also analyzes the possible molecular mechanisms underlying the protective action of these supplements, which may lead a novel therapeutic approach to prevent or attenuate diet-related disease, such as atherosclerosis.

• Mediterranean diet
• atherosclerosis
• bioactive compounds
• cardiovascular disease
• dietary supplements
• functional foods
• immunonutrition
• inflammation

• calcification
• menaquinone-4/Vitamin K2
• transdifferentiation
• vascular smooth muscle cells

• High phosphate
• phosphate
• prophylaxis
• serum phosphate
• vascular pseudo ossification
• vitamin K.

Anticoagulation therapy for mechanical prosthetic valves is limited to vitamin K antagonists, unfractionated heparin and low-molecular-weight-heparin. Other forms of anticoagulation are either contraindicated or have not been well studied. Hence, anticoagulation for preexisting mechanical valves is controversial if vitamin K antagonists are contraindicated. We present a case involving an end-stage-renal disease patient with both mitral and aortic mechanical valves who developed warfarin-induced calciphylaxis.

A 72-year-old male with history of end-stage renal disease, chronic atrial fibrillation and rheumatic heart disease status post mitral and aortic valve replacements presented with complaints of left thigh erythema with skin induration. Despite multiple antibiotic regimens for presumed cellulitis, the skin lesions progressed to necrotic ulcers. A biopsy revealed evidence of calciphylaxis; a lethal condition typically associated with renal disease. The patient was on warfarin for anticoagulation of his mechanical heart valves as well as prophylactically for atrial fibrillation. Warfarin contributes to the development of calciphylaxis and needed to be exchanged to avoid progression of the ulceration. The only other acceptable option for long-term anticoagulation was subcutaneous unfractionated heparin but this approach was not taken. The patient suffered from further sequelae of calciphylaxis and eventually expired.

Calciphylaxis is a rare, serious disorder that presents with skin ischemia and necrosis mainly in end-stage renal disease patients. The pathogenesis and treatment are poorly understood and the prognosis remains grave. It is proposed that certain medications, including warfarin, contribute to its evolution. The optimal anticoagulation therapy in those with concomitant warfarin-induced calciphylaxis and mechanical valves is undetermined. Further studies are essential to establish new anticoagulation regimens in these devastating circumstances.

• CO2
• Vitamin K
• aging
• biosynthesis
• carboxylation
• chronic disease
• extraction
• microalgae
• phylloquinone
• supercritical
• vitamin K1