Publications (37) View all
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Article: Identification of a novel factor XI gene mutational event in a Dutch Caucasian family with inherited factor XI deficiency.
Thrombosis and Haemostasis 03/2013; 109(6). · 5.04 Impact Factor -
Article: Decreased free protein S levels and venous thrombosis in the acute setting, a case-control study.
Thrombosis Research 07/2011; 128(5):501-2. · 2.44 Impact Factor -
Article: Associations between high factor VIII and low free protein S levels with traditional arterial thrombotic risk factors and their risk on arterial thrombosis: results from a retrospective family cohort study.
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ABSTRACT: Whether high factor (F)VIII and low free protein S levels are risk factors for arterial thrombosis is unclarified. In a post-hoc analysis of a single-centre retrospective family cohort, we determined if these two proteins could increase the risk of arterial thrombosis. In total, 1399 relatives were analysed. Annual incidence in relatives with high FVIII levels was 0.29% (95%CI, 0.22-0.38) compared to 0.13% (95%CI, 0.09-0.19) in relatives with normal FVIII levels. In relatives with low free protein S levels, this risk was 0.26% (95%CI, 0.16-0.40), compared to 0.14% (95%CI, 0.10-0.20) in relatives with normal free protein S levels. Mean FVIII levels adjusted for age and sex were 11 IU/dL, 18 IU/dL, and 21 IU/dL higher in relatives with hypertension, diabetes mellitus, and obesity as compared to relatives without these arterial thrombotic risk factors. Moreover, a dose response relation between increasing FVIII and body mass index was found. None of these associations were shown for free protein S. High FVIII and low free protein S levels seemed to be mild risk factors for arterial thrombosis. High FVIII levels were particularly observed in relatives with traditional arterial thrombotic risk factors. Free protein S levels were not influenced by these thrombotic risk factors. This assumes that low free protein S levels were genetically determined.Thrombosis Research 10/2010; 126(4):e249-54. · 2.44 Impact Factor -
Article: Low cut-off values increase diagnostic performance of protein S assays.
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ABSTRACT: Conflicting data have been reported on the accuracy of protein S (PS) assays for detection of hereditary PS deficiency. In this study we assessed the diagnostic performance of two total PS antigen assays, four free PS assays and three PS activity assays in a group of 28 heterozygous carriers of mutations in PROS1 and 165 control subjects. Several control groups were formed, one of healthy volunteers and - because PS levels are influenced by oral contraception and pregnancy, and assays measuring PS activity may be influenced by the presence of the factor V Leiden mutation -, we also investigated the influences of these factors. All nine PS assays detected significantly reduced PS levels in subjects with a PROS1 mutation. Eight out of nine PS assays showed a 100% sensitivity and 100% specificity to detect heterozygous carriers of mutations in PROS1 with values far below the lower limit of the reference values obtained from healthy volunteers. Low specificities were found in subjects with a factor V Leiden mutation and in pregnant women. At lower cut-off levels, equal to the highest PS value found in heterozygous carriers of mutations in PROS1, the specificity considerably increased in these subjects. When using low cut-off levels equal to the highest PS value found in heterozygous carriers of mutations in PROS1, ensuring 100% sensitivity, the specificity in all study groups increases considerably, by which misclassification can be maximally avoided.Thrombosis and Haemostasis 09/2010; 104(3):618-25. · 5.04 Impact Factor -
Article: Thrombocytopenia affects plasmatic coagulation as measured by thrombelastography.
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ABSTRACT: Thrombelastography (TEG) is used as a point-of-care test of hemostasis. Different components of the test tracing are considered to reflect various parts of the hemostatic system and to distinguish low platelet count, platelet dysfunction or both from lack of plasmatic coagulation factors. To analyze the influence of one single element of the coagulation system, namely the platelet count, we used TEG serially in patients with well documented transient thrombocytopenia. A total of 189 TEG analyses were performed from 16 patients with a hematological malignancy in remission, receiving consolidation courses of chemotherapy. TEG outcomes using unmanipulated and citrated blood samples at a median of 11 times (range 1-17) in the same patients during the decrease of platelet count in response to chemotherapy were compared with outcomes in 120 healthy adults from various age categories. We found a correlation (r = 0.7, P < 0.001) between TEG clot strength (maximum amplitude) and platelet count. Moreover, platelet count was correlated respectively with the initial rate of clot formation (reaction time and clotting time), the rate of clot growth (alpha angle), and also with maximum thrombus generation, time to maximum thrombus generation and total thrombus generation. We conclude that platelet count not only affects the strength of clot formation, as was expected, but also all other phases of plasmatic coagulation. Citration of the blood sample, aiming at easy storage of the material, masked some of the important biological parameters of coagulation.Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 07/2010; 21(5):389-97. · 1.25 Impact Factor
