Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new vitamin-K research articles will be listed here shortly after becoming available to us.
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Medical research on vitamin-K
J Gen Intern Med. 2008 Jun 20;
Pernod G, Labarère J, Yver J, Satger B, Allenet B, Berremili T, Fontaine M, Franco G, Bosson JL
BACKGROUND: Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown. OBJECTIVE: To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications. DESIGN/PARTICIPANTS: We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events. RESULTS: During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 - 0.7, p < 0.01). CONCLUSIONS: Patient education using an educational program reduced VKA-related adverse event rates.
Predictors of unstable anticoagulation in African Americans.
J Thromb Thrombolysis. 2008 Jun 19;
Cavallari LH, Aston JL, Momary KM, Shapiro NL, Patel SR, Nutescu EA
Objective We sought to identify contributors to unstable anticoagulation in African Americans. Patients and methods Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range. Results The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation. Conclusion We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.
Management of venous thromboembolism in patients with cancer: role of dalteparin.
Vasc Health Risk Manag. 2008; 4(2): 279-87
Linkins LA
Cancer is a major risk factor for the development of venous thromboembolism (VTE). Conventional anticoagulant therapy with a vitamin K antagonist is more problematic in cancer patients due to an increased risk of recurrent VTE, and an increased risk of anticoagulant-related bleeding. In recent years, there has been a shift toward treating cancer patients with VTE with extended duration dalteparin. Dalteparin, a low-molecular-weight heparin, has been shown to be more effective, and as safe as conventional anticoagulant therapy, in cancer patients with VTE. This paper will (a) review the relationship between cancer and VTE, and (b) provide an overview of the role of dalteparin in the management of VTE in patients with cancer.
Environ Health Perspect. 2008 Jun; 116(6): 784-90
Theppeang K, Glass TA, Bandeen-Roche K, Todd AC, Rohde CA, Links JM, Schwartz BS
OBJECTIVE: The objective of this study was to evaluate the relations between bone mineral density (BMD) and lead in blood, tibia, and patella and to investigate how BMD modifies these lead biomarkers in older women. DESIGN: In this study, we used cross-sectional analysis. PARTICIPANTS: We studied 112 women, 50-70 years of age, including both whites and African Americans, residing in Baltimore, Maryland. MEASUREMENTS: We measured lumbar spine BMD, blood and bone lead by dual energy X-ray absorptiometry, anodic stripping voltammetry, and (109)Cd-induced K-shell X-ray fluorescence, respectively. We measured vitamin D receptor and apolipoprotein E (APOE) genotypes using standard methods. RESULTS: Mean (+/- SD) BMD and lead levels in blood, tibia, and patella were 1.02 +/- 0.16 g/cm(2), 3.3 +/- 2.2 mug/dL, 19.7 +/- 13.2 mug/g, and 5.7 +/- 15.3 mug/g, respectively. In adjusted analysis, higher BMD was associated with higher tibia lead levels (p = 0.03). BMD was not associated with lead levels in blood or patella. There was evidence of significant effect modification by BMD on relations of physical activity with blood lead levels and by APOE genotype on relations of BMD with tibia lead levels. There was no evidence that BMD modified relations between tibia lead or patella lead and blood lead levels. CONCLUSIONS: We believe that BMD represents the capacity of bone that can store lead, by substitution for calcium, and thus the findings may have relevance for effect-size estimates in persons with higher BMD. RELEVANCE TO CLINICAL PRACTICE: The results have implications for changes in lead kinetics with aging, and thus the related risk of health effects associated with substantial early- and midlife lead exposure in older persons.
Thromb J. 2008 Jun 17; 6(1): 7
Haug KB, Sharikabad MN, Kringen MK, Narum S, Sjaatil ST, Wiik Johansen P, Kierulf P, Seljeflot I, Arnesen H, Brors O
ABSTRACT: BACKGROUND: Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA) alone. AIMS: The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR). METHODS: Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC) before PCR amplification (LightCycler) and melting point analysis. RESULTS: The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3 % , 5.7 % and 36.6 % respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5 % to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2 % of the dose variation. CONCLUSION: CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.
Adherence to K/DOQI guidelines for calcium-based phosphate binders in clinical practice.
J Ren Nutr. 2008 Jul; 18(4): 370-4
Shastri J, Tran A, Covit A, Pepe J, Sherman RA
OBJECTIVE: The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism in chronic kidney disease recommend that calcium-based phosphate binders (CBPBs) be used in limited doses and be reduced or withheld when albumin-adjusted serum calcium exceeds target values, or when parathyroid hormone is below the target range. We sought to assess the pattern of CBPB use in a clinical practice setting. DESIGN: This was a retrospective review. PATIENTS: We reviewed 283 patients at three hemodialysis units in New York and New Jersey in which 39 physicians practice. METHODS: Data collected included intact parathyroid hormone levels (from February and May, 2006), blood chemistries (from April and May, 2006), and the use of CBPBs, vitamin D, and cinacalcet. The use of CBPBs was classified as "consistent" or "inconsistent" with the guidelines 1 month after the blood tests of May 2006 (to allow time for dosing adjustments). Because cinacalcet was not available when the K/DOQI guidelines were published, a failure to reduce or stop CBPBs in the presence of elevated calcium levels was still considered to be "consistent" use if cinacalcet was initiated in the appropriate time frame (5 patients). RESULTS: CBPBs were used in 172 of 283 patients (61%). In 10% (17 patients), doses exceeded the 1500-mg limit for calcium. Adjusted serum calcium levels exceeded 2.5 mmol/L (10.2 mg/dL) in 8 cases; CBPBs were not reduced or stopped in any of these. Similarly, CBPBs were reduced in only 2 of 27 patients on vitamin D, with an adjusted serum calcium level of 2.38 to 255 mmol/L (9.5 to 10.2 mg/dL). In all 10 patients with consecutive intact parathyroid hormone values of less than 150 ng/L (150 pg/mL), CBPBs were not discontinued or reduced. CONCLUSIONS: Overall, 50 of 172 patients (29%) receiving CBPBs did so in a manner inconsistent with K/DOQI guidelines. The reasons for this inconsistency are speculative, and may include disagreement with the opinion-based recommendations, insufficient knowledge of the guidelines, or individual patient considerations (including cost, tolerance, and effectiveness).
Vitamin k status of canadian peritoneal dialysis patients.
Perit Dial Int. 2008 Jul-Aug; 28(4): 415-8
Holden RM, Iliescu E, Morton AR, Booth SL
[CYP2D6-, CYP2C9- and CYP2C19-based dose adjustments : When do they make sense?]
Internist (Berl). 2008 Jun 14;
Seeringer A, Kirchheiner J
The efficacy of a drug therapy is influenced by many different factors such as age, weight, comorbidity and co-medication, which vary between patients, as well as fixed parameters such as gender and pharmacogenetic characteristics. Many enzymes involved in drug metabolism are genetically polymorphic, which means that their activity differs depending on a certain genotype. Drugs will be metabolized slowly in individuals who are carriers of a genetic polymorphism, leading to absent or decreased enzyme activity, and these individuals are at particular risk for adverse drug reactions or therapeutic failure. On the other hand, drug therapy could be ineffective if the drug is metabolized too fast because of a genetic polymorphism. The knowledge of these polymorphisms before beginning a drug therapy could help in choosing the right drug in a safe dosage. In particular, three polymorphic drug metabolizing enzymes are responsible for the metabolism of many commonly used drugs. These enzymes, belonging to the cytochrome P450 (CYP) family, are CYP2D6, CYP2C9 and CYP2C19. Besides beta-blockers and antidepressants, several drugs used in cancer therapy, as well as PPIs, NSAIDs, vitamin K-antagonists and oral antidiabetics are metabolized via these enzymes. Especially for drugs with a narrow therapeutic index and a high risk for the development of adverse drug effects, genotyping could be helpful when choosing the right drug in the optimal dosage for individual patients.
J Pharm Pharmacol. 2008 Jul; 60(7): 889-93
Tirapelli CR, Resstel LB, de Oliveira AM, Corrêa FM
Phylloquinone (vitamin K(1), VK(1)) is widely used therapeutically and intravenous administration of this quinone can induce hypotension. We aimed to investigate the mechanisms underlying the effects induced by VK(1) on arterial blood pressure. With this purpose a catheter was inserted into the abdominal aorta of male Wistar rats for blood pressure and heart rate recording. Bolus intravenous injection of VK(1) (0.5-20 mgkg(-1)) produced a transient increase in blood pressure followed by a fall. Both the pressor and depressor response induced by VK(1) were dose-dependent. On the other hand, intravenous injection of VK(1) did not alter heart rate. The nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10 and 20 mgkg(-1)) reduced both the increase and decrease in blood pressure induced by VK(1) (5 mgkg(-1)). On the other hand, indometacin (10 mg kg(-1)), a non-selective cyclooxygenase inhibitor, did not alter the increase in mean arterial pressure (MAP) induced by VK(1). However, VK(1)-induced fall in MAP was significantly attenuated by indometacin. We concluded that VK(1) induces a dose-dependent effect on blood pressure that consists of an acute increase followed by a more sustained decrease in MAP. The hypotension induced by VK(1) involves the activation of the nitric oxide (NO) pathway and the release of vasodilator prostanoid(s).
Ned Tijdschr Geneeskd. 2008 May 3; 152(18): 1042-6
Zelis M, Zweegman S, van der Meer FJ, Kramer MH, Smulders YM
--In users of vitamin K-antagonists (VKA), antibiotics can lead to excessive anticoagulation. --It is unclear what the optimal policy is for prevention of an excessive anticoagulant effect during use of antibiotics. --This article describes the increased sensitivity to VKA during use of antibiotics, and also provides a practical recommendation for the correct method for use of antibiotics in combination with VKA treatment. --During use of antibiotics for more than one day, the prothrombin time-'international normalized ratio' (PTT-INR) must be checked both after 3 and after 7 days, and the dose of VKA must be adapted if necessary. --Use of co-trimoxazole for more than one day should, if possible, be avoided.