Star Medical Diagnostic Center

Rotterdam, Netherlands

Star Medical Diagnostic Center

Rotterdam, Netherlands
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Biedermann J.S.,Erasmus Medical Center | Biedermann J.S.,Star Medical Diagnostic Center | Rademacher W.M.H.,Academic Center for Dentistry Amsterdam | Hazendonk H.C.A.M.,Erasmus Medical Center | And 5 more authors.
Thrombosis and Haemostasis | Year: 2017

Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1–3 elements) and extensive high-risk (e. g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after lowrisk and high-risk dental procedures in patients on VKA. Perioperative management strategy, procedure risk, and 30-day outcomes were assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004 (3.3 %) low-risk and 21/325 (6.5 %) highrisk procedures (p=0.006). In low-risk procedures, VKA continuation with tranexamic acid mouthwash was associated with a lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23–0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24–1.00], and a similar risk as interruption without bridging [OR=1.44, 95 %CI 0.62–3.64]. In high-risk procedures, VKA continuation was associated with an increased OCB risk compared to interruption [OR=3.08, 95 %CI 1.05–9.04]. Multivariate analyses revealed bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR before the procedure as strongest predictors of OCB. Non-oral cavity bleeding (NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03–3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly related to perioperative management and differed between low-risk and highrisk procedures. Perioperative management should be differentiated accordingly. © Schattauer 2017.


Biedermann J.S.,Erasmus Medical Center | Biedermann J.S.,Star Medical Diagnostic Center | van den Besselaar A.M.H.P.,Leiden University | de Maat M.P.M.,Erasmus Medical Center | And 3 more authors.
Journal of Thrombosis and Haemostasis | Year: 2017

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Summary: Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL−1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5–3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL−1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences regarding FVII sensitivity exist between various thromboplastins used for VKA monitoring. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Therefore, thromboplastin choice may affect FVII-mediated INR stability. © 2017 International Society on Thrombosis and Haemostasis


De Keyser C.E.,Erasmus University Rotterdam | Becker M.L.,Erasmus University Rotterdam | Hofman A.,Erasmus University Rotterdam | Lous J.J.,Star Medical Diagnostic Center | And 7 more authors.
Pharmacogenetics and Genomics | Year: 2015

OBJECTIVE: Recently, the minor allele of the rs13064411A>G polymorphism in the WD repeat domain 52 (WDR52) gene was associated with increased statin-induced proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and with LDL cholesterol response to statins. PCSK9 promotes LDL receptor degradation, leading to increased serum LDL cholesterol. We investigated whether the polymorphism was associated with cholesterol response to statins. METHODS: We identified 1105 current, 322 past, and 4831 never statin users during follow-up in the prospective population-based Rotterdam Study. The mean delta total, LDL, and HDL cholesterol levels between current and no current statin users with the same number of minor alleles were analyzed using random-effect repeated measurements. We adjusted for age, sex, number of cholesterol measurements, and follow-up time. RESULTS: Compared with no users with the same genotype, current statin users carrying a minor allele showed a statistically significantly lower delta total and LDL cholesterol compared with reference homozygous major allele carriers [total: Δ=0.551mmol/l (AG+GG) vs. Δ=0.732mmol/l (AA), Pinteraction: 5.2×10-7; LDL: Δ=0.566mmol/l (AG+GG) vs. Δ=0.720mmol/l (AA), Pinteraction: 1.8×10-5]. The effect was stronger in women (Pinteraction: 2.0×10-5 for LDL cholesterol, 8.0×10-6 for total cholesterol) and in high-dose users (defined daily doses>1.00) (Pinteraction: 7.0×10-5 for LDL cholesterol, Pinteraction: 0.081 for total cholesterol). The polymorphism was not associated with HDL cholesterol in current statin users, or with total, LDL and HDL cholesterol in never statin users. CONCLUSION: The minor G allele of the rs13064411 polymorphism, associated with statin-induced PCSK9-levels, was associated with a decreased LDL-lowering and total cholesterol-lowering response to statins. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Teichert M.,Erasmus Medical Center | Teichert M.,Scientific Institute Dutch Pharmacists | van Noord C.,Erasmus Medical Center | Uitterlinden A.G.,Erasmus Medical Center | And 7 more authors.
British Journal of Haematology | Year: 2011

In the Netherlands, several reports have described a potentiation of acenocoumarol-induced anticoagulation by co-medication of omeprazole or esomeprazole and competitive inhibition of CYP2C19 has been suggested as a possible mechanism for this interaction. We conducted an observational cohort study to investigate the effects of various proton pump inhibitors (PPIs) on acenocoumarol effectiveness. All 2755 subjects from the Rotterdam Study who received acenocoumarol maintenance treatment between April 1st, 1991 and September 9th, 2009 were followed for events of an international normalized ratio (INR)≥6, until death, end of treatment, or end of the study period. The Andersen-Gill extension of the Cox proportional hazards model was used to calculate risks for repeated events of overanticoagulation in relation to concomitant PPI use. The risk for overanticoagulation was most pronounced for esomeprazole (HR 1·99, 95% CI 1·55-2·55) and lansoprazole (HR 1·49, 95% CI 1·05-2·10). There was also a lower and non-significant risk increase for the other PPIs. We did not detect a modification of these results by CYP2C19*2 genotype. Caution should be paid to co-medication with esomeprazole and lansoprazole during acenocoumarol treatment and possibly also with other PPIs. © 2011 Blackwell Publishing Ltd.


Teichert M.,Erasmus Medical Center | Teichert M.,Scientific Institute Dutch Pharmacists | Visser L.E.,Erasmus Medical Center | Uitterlinden A.G.,Erasmus Medical Center | And 6 more authors.
British Journal of Clinical Pharmacology | Year: 2011

AIM The aim of this study was to investigate the effects of co-medication with selective serotonin re-uptake inhibitors (SSRIs) on overanticoagulation during acenocoumarol maintenance treatment. METHODS All subjects from The Rotterdam Study who received acenocoumarol maintenance treatment between April 1 1991 and September 9 2009 were followed for the event of an international normalized ratio (INR) ≥6, until death, end of treatment or end of the study period. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant SSRI use were calculated. RESULTS The risk for overanticoagulation during acenocoumarol maintenance treatment was increased in combination with fluvoxamine (HR 2.63, 95% CI 1.49, 4.66) and venlafaxine (HR 2.19, 95% CI 1.21, 3.99). There was no increase in risk for the other SSRIs, but numbers of exposed cases were low for all SSRIs except paroxetine. CONCLUSION Fluvoxamine and venlafaxine were associated with a more than double risk of INR values ≥6 in acenocoumarol treated subjects. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.


Teichert M.,Erasmus Medical Center | Teichert M.,Scientific Institute Dutch Pharmacists | Eijgelsheim M.,Erasmus Medical Center | Uitterlinden A.G.,Erasmus Medical Center | And 7 more authors.
Pharmacogenetics and Genomics | Year: 2011

Background: Genome-wide association studies (GWAS) on warfarin and acenocoumarol showed that interindividual dosage variation is mainly associated with single nucleotide polymorphisms (SNPs) in VKORC1 and to a lesser extent in CYP2C9 and CYP4F2. For phenprocoumon dosage, the genes encoding CYP3A4 and ApoE might play a role. OBJECTIVE: To assess the association between common genetic variants within VKORC1, CYP2C9, CYP4F2, CYP3A4, and ApoE and phenprocoumon maintenance dosage, and to identify novel signals using GWAS. METHODS: We selected all participants from the Rotterdam study who were treated with phenprocoumon. For each SNP, we tested the association between the above-mentioned genotypes and age, sex, body mass index, and target INR adjusted-phenprocoumon maintenance dosage. Results: Within our study population (N=244), VKORC1, CYP2C9, CYP4F2 genotypes together explained 46% of phenprocoumon maintenance dosage variation. Each additional VKORC1 variant allele reduced phenprocoumon maintenance dosage by 4.8 mg/week (P<0.0001) and each additional CYP2C9 variant allele by 2.2 mg/week (P=0.002). Each additional variant allele of CYP4F2 increased phenprocoumon dosage by 1.5 mg/week (P=0.022). Variant alleles of CYP3A41*B and ApoE showed no association with phenprocoumon dosage. Genome-wide significant SNPs were all related to VKORC1 activity. Best associated were two SNPs in complete linkage disequilibrium with each other and with SNPs within VKORC1: rs10871454 [Syntaxin 4A (STX4A)] and rs11150604 (ZNF646), each with a P value of 2.1×10- 22. Each reduced phenprocoumon maintenance dosage weekly by 4.9 mg per variant allele. Conclusion: Similar to earlier findings with warfarin and acenocoumarol, phenprocoumon maintenance dosage depended on polymorphisms in the VKORC1 gene. CYP2C9 and CYP4F2 were of modest relevance. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


van Blijderveen J.C.,Erasmus Medical Center | Verhamme K.M.,Erasmus Medical Center | Zietse R.,Erasmus Medical Center | Visser L.E.,Erasmus Medical Center | And 7 more authors.
Journal of Nephrology | Year: 2013

Background: Recent studies suggest that overanticoagulation impairs renal function in patients on warfarin therapy, due to renal tubular obstruction from glomerular hemorrhage. Methods: Data from the Rotterdam Study (The Netherlands), a prospective population-based cohort study of patients 55 years and older, were used for this study. Information on vitamin K antagonist (VKA) therapy was obtained from the regional anticoagulation clinic, where prothrombin times were monitored every 1-6 weeks depending on target level and stability of the international normalized ratio (INR). Linear regression was performed to study the association between the cumulative number of instances of overanticoagulation (defined as a measurement of an INR >6.0) and the change in renal function between baseline and third examination round based on estimated glomerular filtration rate (CKD-EPI equation). Age, sex, baseline renal function, baseline and incident heart failure, and indication for VKA therapy were included as potential confounders. Results: Information was available for analysis on 2,802 study participants in whom overanticoagulation was significantly associated with a decline in renal function, after adjustment for confounding by age, sex, heart failure, baseline glomerular filtration rate and indication for VKA therapy (-0.180 ml/min per 1.73 m2 per year per event for INR >6.0, p = 0.030). Conclusions: Overanticoagulation (INR >6.0) is associated with a decline in renal function. Further studies are needed to evaluate the causal role of different degrees of overanticoagulation, including transient effects, in high-risk groups, and the association with the new oral anticoagulants. © 2013 Società Italiana di Nefrologia.


van den Besselaar A.M.H.P.,Leiden University | Biedermann J.S.,Erasmus Medical Center | Biedermann J.S.,Star Medical Diagnostic Center | Kruip M.J.H.A.,Erasmus Medical Center | Kruip M.J.H.A.,Star Medical Diagnostic Center
Thrombosis and Haemostasis | Year: 2015

Many patients treated with vitamin K antagonists (VKA) determine their INR using point-of-care (POC) whole blood coagulation monitors. The primary aim of the present study was to assess the INR within-subject variation in self-testing patients receiving a constant dose of VKA. The second aim of the study was to derive INR imprecision goals for whole blood coagulation monitors. Analytical performance goals for INR measurement can be derived from the average biological within-subject variation. Fifty-six Thrombosis Centres in the Netherlands were invited to select self-testing patients who were receiving a constant dose of either acenocoumarol or phenprocoumon for at least six consecutive INR measurements. In each patient, the coefficient of variation (CV) of INRs was calculated. One Thrombosis Centre selected regular patients being monitored with a POC device by professional staff. Sixteen Dutch Thrombosis Centres provided results for 322 selected patients, all using the CoaguChek XS. The median withinsubject CV in patients receiving acenocoumarol (10.2 %) was significantly higher than the median CV in patients receiving phenprocoumon (8.6 %) (p = 0.001). The median CV in low-target intensity acenocoumarol self-testing patients (10.4 %) was similar to the median CV in regular patients monitored by professional staff (10.2 %). Desirable INR analytical imprecision goals for POC monitoring with CoaguChek XS in patients receiving either low-target intensity acenocoumarol or phenprocoumon were 5.1 % and 4.3 %, respectively. The approximate average value for the imprecision of the CoaguChek XS, i. e. 4 %, is in agreement with these goals. © Schattauer 2015.


Klijs B.,Erasmus University Rotterdam | Otto S.J.,Erasmus University Rotterdam | Heine R.J.,VU University Amsterdam | Heine R.J.,Eli Lilly and Company | And 3 more authors.
BMC Public Health | Year: 2012

Background: We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods. Between 2006 and 2007, 79,142 inhabitants of two Dutch municipalities aged 40-74 years were approached to participate in screening. Eligible participants had a self-reported waist circumference of 80 cm for women and 94 cm for men, and no known pre-existing diabetes. Of the respondents (n=20,578; response rate 26%), 16,135 were abdominally obese. In total, 10,609 individuals gave written informed consent for participation and were randomized into either the screening (n=5305) or the control arm (n=5304). Participants in the screening arm were invited to have their fasting plasma glucose (FPG) measured and were referred to their general practitioner (GP) if it was 6.1 mmol/L. In addition, blood lipids were determined in the screening arm, because abdominal obesity is often associated with cardiovascular risk factors. Participants in both arms received written healthy lifestyle information. Between-group differences were analyzed with Chi-square tests and logistic regression (categorical variables) and unpaired t-tests (continuous variables). Results: The screening attendance rate was 84.1%. Attending screening was associated with age at randomization (OR=1.03, 95% CI 1.02-1.04), being married (OR=1.57, 95% CI 1.33-1.83) and not-smoking currently (OR=0.52, 95% CI 0.44-0.62). Of the individuals screened, 5.6% had hyperglycemia, and a further 11.6% had an estimated absolute cardiovascular disease risk of 5% or higher, according to the Systematic Coronary Risk Evaluation risk model. These participants were referred to their GP. Conclusions: Self-reported home-assessed waist circumference could feasibly detect persons at high risk of hyperglycemia or cardiovascular disease. Continuation of the large-scale RCT is warranted to test the hypothesis that targeted population-based screening for type 2 diabetes leads to a significant reduction in cardiovascular morbidity and mortality. © 2012 Klijs et al.; licensee BioMed Central Ltd.


PubMed | Erasmus Medical Center, Leiden University and Star Medical Diagnostic Center
Type: Journal Article | Journal: Journal of thrombosis and haemostasis : JTH | Year: 2016

Point-of-care (POC) international normalized ratio (INR) monitoring by healthcare professionals could eliminate the need for venous blood sampling in non-self-monitoring (NSM) patients on vitamin K antagonists (VKA). However, few studies have investigated the impact of POC INR monitoring on the quality of treatment in these patients and real-world data on this issue are lacking.To investigate the safety, efficacy and quality of anticoagulant control during POC INR monitoring as compared with laboratory INR monitoring in NSM patients.We performed a retrospective cohort study using data from the anticoagulation clinic of the Star-Medical Diagnostic Center (Rotterdam, the Netherlands). Patients who received treatment with VKA between 29 May 2012 and 29 May 2014 were eligible. Percentage of time in therapeutic range (TTR) and incidence rates of major clinical events (all-cause mortality, hospitalization, major bleeding and ischemic stroke) were compared for the year before and year after introduction of POC monitoring. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for major clinical events between exposure groups.In total, 1973 patients during the 1-year laboratory-monitoring observation period and 1959 patients during the 1-year POC-monitoring observation period were included. Median TTR was significantly lower during POC monitoring (77.9%; 95% CI, 67.2-87.4) than during laboratory INR monitoring (81.0%; 95% CI, 71.1-90.5). Adjusted hazard ratios for major clinical events were all around unity.Although associated with lower TTR, POC INR monitoring is a safe and effective alternative to laboratory INR monitoring in NSM patients on VKA.

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