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Biomedical subjects

C Kluft

Publications and source records attributed to C Kluft.

At least 37 records · Page 2Linked to original sources
PubMed2001

Disagreement between bedside and laboratory activated partial thromboplastin time and international normalized ratio for various novel anticoagulants.

During studies on warfarin, heparin and various anticoagulants with novel mechanisms of action, the activated partial thromboplastin time (aPTT) and the (apparent) international normalized ratio (INR) from a bedside monitor (Coagucheck Plus(R)) were compared with laboratory assay results. Data were compared using the Bland and Altman method of comparison where systematic differences result in significant slopes of the regression line. During heparin treatment, the bedside monitor largely underestimated the aPTT (slope = -0.80). During treatment with the direct thrombin inhibitor napsagatran (slope = 0.99), the pentasaccharides Org31540/SR90107A (slope = 0.77) and SanOrg34006 (slope = 0.35), and warfarin (slope = 0.60), the bedside monitor underestimated the aPTT at lower aPTT levels, while at higher aPTT levels it overestimated the laboratory values. The bedside monitor slightly overestimated the INR during treatment with warfarin (slope = 0.33). Apparent INR was largely overestimated during treatment with Org31540/SR90107A (slope = 1.38), SanOrg34006 (slope = 0.97), Napsagatran (slope = 1.23), and recombinant tissue factor pathway inhibitor (slope = 1.48, P < 0.001 for all regression lines). These results indicate that a substantial disagreement in aPTT or (apparent) INR exists between the bedside monitor and laboratory assay during treatment with the studied 'classic' and novel anticoagulants. The amount of disagreement depended on the anticoagulant given.

Anticoagulants↗
PubMed2001

Activation products of the haemostatic system in coronary, cerebrovascular and peripheral arterial disease.

To determine the presence of a 'hypercoagulable state' as assessed by indices of thrombin and plasmin generation and of the amount of fibrin that is lysed, in patients with stable coronary, cerebral and peripheral arterial disease a population-based cross-sectional study was performed. From a population-based cohort comprising 7983 men and women aged 55 years and over, we randomly selected 127 subjects with a history of myocardial infarction, 124 with a history of stroke and/or transient ischemic attack, 131 patients with peripheral arterial disease and 263 control subjects in the same age group without arterial disease. Subjects using anticoagulant drugs were not selected. F1+2, TAT, and PAP were not associated with a history of cardiovascular events, nor with peripheral arterial disease. In contrast, positive associations were found for D-Dimer. Mean D-Dimer level was 40 microg/l (95% CI 35, 44) in control subjects; 53 microg/l (47, 61) in those with a history of myocardial infarction and 51 microg/l (45, 58) in those with a history of stroke and or transient ischemic attack. D-Dimer increased gradually with increasing severity of peripheral atherosclerosis; a decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an increase in D-Dimer of 3.9 microg/l (p<0.01). This was more pronounced in subjects with higher F1+2, TAT and PAP concentration. In conclusion, the markers of onset of coagulation F1+2, TAT and PAP are not associated with the presence of arterial disease, but increased levels of these markers are necessary for the positive association between D-Dimer and arterial disease.

Aged↗
PubMed2001

Determination of the habitual low blood level of C-reactive protein in individuals.

In order to use C-reactive protein (CRP) in risk prediction in individuals, it is necessary to know how to obtain the habitual level of an individual and hence its biological variations: i.e. longitudinal variability within subjects and variability between individuals. This paper provides data on biological variability that is used to propose a strategy for assessing individual low levels of CRP. The longitudinal variability in individuals (intraindividual variability) is essential to know, but only reported in a very limited way. Additional data were calculated from in-house and requested databases for periods of follow-up from 5 days to 1 year. The intraindividual coefficient of variation (CVi) was found to be rather similar for several groups and periods and on average was approximately 30%. Reported analytical coefficients of variation of commercial and in-house methods generally are below 6%, which is well below the desired limit of half the CVi. The distribution of CRP in apparently healthy individuals is wide and skewed with interquartile values ranging between 150-250% of the median and an estimate of the composite coefficient of variation (CVc) of approximately 120%. The distribution is equally broad in several other groups studied such as type II diabetics and pregnant women. It is concluded that the coefficient of variation for the determination of CRP in a single blood sample is as high as approximately 30%, but that this is acceptable for the reliable positioning of individuals within the distribution of CRP in the group with a CVc as high as -120%. CRP can show unexpected outliers (increases) which can sometimes be explained by information from a short questionnaire and definitely identified by the analysis of a second blood sample after an interval of approximately 2 weeks. Similarly, to ascertain high values in a first sample a second blood sample can be analyzed. It should be noted that, in view of the significant intraindividual variability of CRP, the difference between the first and second values may reach 71%. The large intraindividual variability of CRP approximating 30% renders it difficult to position an individual reliably in smaller categories such as tertiles, quartiles or quintiles of the total distribution. It is suggested that it would be most practical to have a goal of a single decision level or threshold only. Positioning an individual into two groups with equally wide distribution is on the borderline of reliability for one blood sample. Multiple blood samplings are required for smaller categories and higher threshold levels. The use of a decision limit should further acknowledge the limited interclass stability of around r = approximately 0.5 for a single blood sample. The above considerations are summarized in a practical working scheme. This scheme can serve as a basis for further refinement, discussions and development of sampling and decision limits to be selected from medical and economical perspectives and tested in practice.

Biomarkers↗
PubMed2001

Determinants of C-reactive protein concentration in blood.

C-reactive protein (CRP) is a very strong acute phase protein. During the acute phase of disease the CRP concentration can increase up to a thousand-fold. However, a higher CRP concentration is also observed during chronic stages of disease, for example in subjects with chronic bronchitis, periodontal disease or subjects with increased titers of Helicobacter pylori or Chlamydia pneumoniae. The concentration of CRP is also reported to be associated with age, sex, race, smoking, obesity, consumption of coffee and alcohol, stress, physical training, lipid levels, and blood pressure. Statins decrease the CRP concentration whereas estrogen increases it. With regard to most other drugs no consistent relationship has been reported.

Acute Disease↗
PubMed2000

Antibodies to Chlamydia pneumoniae and clinical course in patients with unstable angina pectoris.

Inflammation is one of the most important mechanisms that contribute to coronary artery disease (CAD). One of the micro-organisms that is mentioned as a source of the inflammation is Chlamydia pneumoniae. In this study, we investigated the relationship between titres of IgG and IgA antibodies to C. pneumoniae and the clinical course, during hospitalisation and during an 18-month follow-up, in 211 patients admitted to hospital with unstable angina pectoris. Slightly more patients who were refractory during their hospitalisation were positive for C. pneumoniae antibodies than patients who could be stabilised by drug treatment (53 vs. 43%, for IgG and 16 vs. 11% for IgA, respectively)(n.s.). In logistic regression analysis no significant predictive values were observed for the relationship between antibody titres and clinical course. The antibody titres to C. pneumoniae were lower in the unstable angina patients who had plasma levels of interleukin-10 (IL-10) above 5 pg/ml than in the patients with levels below 5 pg/ml, and higher in smokers than in non-smokers. No associations were observed between antibody titres to C. pneumoniae and C-reactive protein (CRP), interleukin-6 (IL-6), age, total cholesterol levels, fibrin degradation products (FDP), plasminogen activator inhibitor-1 (PAI-1) and erythrocyte sedimentation rate (ESR). In conclusion, there was no significant association between antibody titres to C. pneumoniae and risk of events during hospitalisation and the 18-month follow-up period in patients admitted for unstable angina pectoris.

Angina, Unstable↗
PubMed2000

Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects.

Recent studies indicate that the enzyme paraoxonase may be an important modulator of cardiovascular disease risk because of its ability to protect LDL from oxidation. We tested for association between two functional variants of the paraoxonase gene (Met-55/Leu and Gln-192/Arg) and both all-cause mortality and fatal cardiovascular disease. This was done within a population-based study among subjects aged 85 years and over in a cross-sectional and a prospective design. In the cross-sectional analysis, the distribution of both paraoxonase genotypes was found to be similar in the subset of 364 elderly subjects who were born in Leiden, The Netherlands, as compared with 250 young subjects whose families originated from the same geographical region. The polymorphisms were in strong linkage disequilibrium (P<0.00001) and the frequency of the haplotype carrying both risk alleles was not lower in the elderly than in the young (0.313 vs. 0.284). The complete cohort of 666 elderly subjects was followed over 10 years. The risk of all-cause and cardiovascular mortality was not increased in elderly subjects with the paraoxonase Leu/Leu (RR, 1.1 [95% CI, 0.9-1.5] and 1.3 [95% CI, 0.8-2.0], respectively) or the Arg/Arg genotype (RR, 0. 9 [95% CI, 0.7-1.2] and 0.7 [95% CI, 0.4-1.3], respectively). In a subset of patients with diabetes, the all-cause mortality risk was elevated in Arg/Arg carriers (RR, 2.1 [95% CI, 0.8-5.8]) but this did not reach statistical significance. Analysis of genotype combinations did not yield significant associations with mortality. The paraoxonase gene variants, previously associated with coronary artery disease, are thus not likely to have a major effect on the risk of fatal cardiovascular disease in the population at large. Adverse effects of the gene variants might be observed in subjects exposed to factors that enhance oxidative stress such as diabetes.

Adult↗
PubMed2000

Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals.

OBJECTIVE: Firstly, to study the effect of tea and tea polyphenols on cardiovascular risk indicators of the inflammatory system (IL6, IL1beta and TNF-alpha, CRP), and on haemostasis and endothelial proteins with an acute phase behaviour (fibrinogen, vWF, PAI-1, FVIIa and u-PA). Secondly, to study the relationship between plasma levels of antioxidants (alpha-tocopherol, beta-carotene and vitamin C) and these acute-phase, cardiovascular risk indicators. DESIGN: Randomized study. SUBJECTS: Sixty-four smoking healthy volunteers were recruited by newspaper advertisements; there were five dropouts. INTERVENTION: Four-week administration of black tea, green tea, green tea polyphenol isolate and mineral water ( 13-16 per group). MEASURES: Plasma levels of the inflammatory markers IL6, IL1beta, TNF-alpha, CRP, fibrinogen, vWF, PAI-1, FVIIa and u-PA and of the antioxidants alpha-tocopherol, beta-carotene and vitamin C. RESULTS: Different dosages of tea polyphenols had no effect on inflammation, haemostasis and endothelial markers. There was a significant negative correlation between the levels of the antioxidant beta-carotene and the inflammation markers IL6 and fibrinogen (r = -0.35 and r = -0.37, respectively, P<0.01) in this group of smokers. Remarkably, there was a significant positive correlation between the levels of the antioxidant alpha-tocopherol and the inflammation marker IL6 (r = 0.28, P<0.05). CONCLUSIONS: Tea drinking had no effect on the levels of the inflammation, haemostasis and endothelial cardiovascular risk factors measured. We did observe a relationship between the antioxidant variables alpha-tocopherol and beta-carotene and inflammation markers in this group of healthy smoking subjects.

Acute-Phase Reaction↗
PubMed2000

Fibrin clot formation and lysis: basic mechanisms.

The hemostatic balance, introduced more than 40 years ago, addresses the components and reactions involved in fibrin turnover. Fibrin is placed in the core of this delicate balance. Defects in the mechanisms responsible for fibrin turnover might lead to thrombosis or bleeding, and fibrin consequently is an important substrate in the physiology of hemostasis. This review describes the components and processes involved in fibrin formation and fibrin degradation. Particular emphasis is put on the reactions involved in the conversion of fibrinogen to fibrin, the polymerization of fibrin molecules induced by coagulation factor XIII (FXIII), and the degradation of fibrinogen and fibrin mediated by plasmin and elastase. Furthermore, factors influencing fibrin structure and fibrin breakdown are addressed; in particular polymorphisms in the genes coding for fibrinogen and FXIII, but also the physical and biochemical conditions in which fibrin is formed. The past decades have produced a bulk of biochemical publications reviewing fibrin turnover and fibrin structure, and it has been shown that alterations in fibrin structure are important for the development of various disease conditions, whereas, the architecture of fibrin can be modified by certain drugs and chemical compounds. However, these topics deserve increased attention in clinical settings. Of particular importance might be more detailed clinical studies that review the influence of polymorphisms in the genes coding for the key factors involved in fibrin metabolism on the development of hemostatic diseases, but also the role of elastase-induced fibrin degradation deserves increased attention.

Antithrombins↗
PubMed2000

Performance of semiquantitative and quantitative D-dimer assays in the ECAT external quality assessment program.

D-dimer levels are used in clinical practice as markers for the presence or exclusion of venous thrombosis. Therefore, it is important that the performance of the D-dimer tests is well controlled. One of the components of a laboratory quality program is external quality assessment (EQA). The main aim of EQA is to identify the degree of agreement among laboratories. In addition to identifying the individual laboratory performance, it also identifies the characteristics of the different reagents and methods that are used in different laboratories. Recently, the D-dimer test was included in the ECAT External Quality Assessment program. Eighty-one laboratories in four rounds applied semiquantitative and quantitative D-dimer assays to three samples (concentrations normal, slightly elevated, and elevated). Although the reported values varied widely, the classification of the samples was mostly correct for the normal and the elevated samples. The slightly elevated sample was classified as normal by all laboratories using semiquantitative methods and by 60% of the laboratories using quantitative methods, and this varied between 45% and 86% for the different methods. In conclusion, D-dimer methods show a large variation, and the quality of the D-dimer assessment could be improved by standardization and by using cut-off ranges.

Antifibrinolytic Agents↗
PubMed2000

Effects on haemostasis variables by second and third generation combined oral contraceptives: a review of directly comparative studies.

Previous reports and reviews indicate differences in effects of second and third generation combined oral contraceptives (COCs) on haemostasis variables. This review analyses directly comparative studies on such effects. From the literature, 17 longitudinal comparative studies with parallel groups were retrieved, containing data on comparisons between COCs containing levonorgestrel (second generation COCs) and COCs containing desogestrel, gestodene or norgestimate (third generation COCs) with 30-35 ug ethinylestradiol. Six or more comparisons were available only for fibrinogen, platelet count, antithrombin III, factor VII, factor VIII and factor X. The comparisons reveal a consistently larger increase in factor VII with the third generation COCs compared to the second generation COCs. The effects on factor VII do not coincide in these comparative studies with effects on factor X and prothrombin, rendering a specific sensitivity of the vitamin K-dependent mechanisms for progestogens unlikely. Fibrinogen effects tend to be different for the different progestogens, suggesting a progestogen-specific dependence. Trends in antithrombin III are towards more reduction for the third generation COCs, but the effects are very minor. The effects on factor V suggest a possible progestogen specificity, which may be relevant to explain the difference in APC-resistance between second and third generation of COCs. In general, direct comparisons of effects of different types of COCs on haemostatic variables are available for only a very few factors, which hampers the drawing of general conclusions with respect to haemostatic consequences.

Animals↗
PubMed1999

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Activated Protein C Resistance↗
PubMed1999

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis.

It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in those with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore act as a predictor, not only of disease progression, but also of response to therapy and risk of restenosis.

Anticholesteremic Agents↗