Joost C M Meijers

Academic Medical Center (AMC), Amsterdamo, North Holland, Netherlands

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Publications (352)1912.67 Total impact

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    ABSTRACT: Rationale: Autosomal dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels and increased risk for coronary artery disease (CAD). ADH is caused by mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin 9 (PCSK9). However, in a proportion of ADH cases mutations in these genes are not found. Objective: To identify a fourth locus associated with ADH. Methods and Results: Parametric linkage analysis combined with exome sequencing in a FH4 family resulted in the identification of the variant p.Glu97Asp in STAP1, encoding signal transducing adaptor family member 1. Sanger sequencing of STAP1 in 400 additional unrelated FH4 probands, in which mutations in the established LDL-associated genes were ruled out, identified a second p.Glu97Asp carrier and three additional missense variants, p.Leu69Ser, p.Ile71Thr, and p.Asp207Asn. STAP1 carriers (N=40) showed significantly higher plasma total cholesterol and LDL-c levels compared to non-affected relatives (N=91). Conclusions: We mapped a novel ADH locus at 4p13, and identified four variants in STAP1 that associate with ADH.
    Circulation Research 07/2014; · 11.86 Impact Factor
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    ABSTRACT: Coagulation factor deficiencies are thought to interfere with the detection of the phospholipid-dependent coagulation inhibitor known as lupus anticoagulant (LA). Treatment with vitamin K antagonists (VKA) in particular, is thought to preclude accurate LA assessment. For this reason, the procedure to detect LA includes a mixing test, in which coagulation factor deficiencies are corrected by mixing samples with an equal volume of normal plasma. Despite these mixing tests, interpretation of LA test results is considered difficult in patients receiving high intensity VKA treatment. As a result, VKA treatment is often temporarily discontinued to allow LA assessment. However, whether coagulation factor deficiencies influence LA test results is unclear. We found that neither deficiency of a single coagulation factor, nor a functional coagulation factor deficiency due to high intensity VKA treatment, resulted in false positive dRVVT- or APTT-based (silica clotting time; SCT) LA test results. LA was readily detected in unmixed samples from VKA-treated LA-positive patients with both dRVVT and SCT reagents. VKA treatment caused an underestimation of the strength of the LA with SCT reagents, but did not lead to misclassification of LA status. Although mixing with normal plasma during both screen and confirm tests allowed more accurate assessment of the strength of the LA with SCT reagents in samples with an international normalised >2.5, the mixing procedure itself lead to misclassification of LA in weakly positive samples from patients not treated with VKA. Based on these findings, we conclude that mixing studies are not necessary during LA-assessment.
    Thrombosis and haemostasis. 07/2014; 112(4).
  • T. Plug, G. Kramer, J. C.M. Meijers
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    ABSTRACT: BackgroundTAFI is a proenzyme that links coagulation and fibrinolysis. TAFI can be activated by thrombin, the thrombin/thrombomodulin (IIa/TM) complex and plasmin by cleaving off the first 92 amino acids from the enzyme. In silico analysis of the TAFI sequence revealed a potential thrombin cleavage site at Arg12. The aim of this study was to determine whether TAFI can be cleaved at Arg12 and if this cleavage plays a role in TAFI activation.MethodsA peptide based on the first 18 amino acids of TAFI was used to determine whether thrombin was able to cleave at Arg12. Mass spectrometry was performed to determine if the Arg12 cleaved peptide was released from full-length TAFI. Furthermore, a TAFI mutant in which Arg12 was replaced by a glutamine (TAFI-R12Q) was constructed and characterized with respect to its activation kinetics.ResultsThe peptide and mass spectrometry data showed that thrombin was able to cleave TAFI at Arg12, but with low efficiency in full-length TAFI. Characterisation of the TAFI-R12Q mutant showed no difference in thrombin-mediated activation compared to wild-type TAFI. However, there was a ~60-fold impairment in TAFI activation of TAFI-R12Q by the IIa/TM complex.Conclusions Arg12 of TAFI plays an important role in thrombomodulin-mediated TAFI activation by thrombin. Thrombin is able to cleave TAFI at Arg12, but it remains to be determined if Arg12 is part of an exosite for thrombomodulin or that cleavage at Arg12 accelerates thrombomodulin-mediated TAFI activation.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 07/2014; · 6.08 Impact Factor
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    ABSTRACT: Coagulation factor XI is proposed as therapeutic target for anticoagulation. However, it is still unclear whether the antithrombotic properties of factor XI inhibitors influence atherosclerotic disease and atherothrombosis. Our aim is to investigate whether factor XI antisense oligonucleotides could prevent thrombus formation on acutely ruptured atherosclerotic plaques.
    Arteriosclerosis Thrombosis and Vascular Biology 06/2014; · 6.34 Impact Factor
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    ABSTRACT: Atherothrombosis is the main cause of myocardial infarction and ischemic stroke. Although the extrinsic (tissue factor-factor VIIa [FVIIa]) pathway is considered as a major trigger of coagulation in atherothrombosis, the role of the intrinsic coagulation pathway via coagulation FXII herein is unknown. Here, we studied the roles of the extrinsic and intrinsic coagulation pathways in thrombus formation on atherosclerotic plaques both in vivo and ex vivo.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; · 6.34 Impact Factor
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    ABSTRACT: Recombinant factor VIIa (rFVIIa) is registered for treatment of inhibitor-complicated haemophilia, and a once-daily prophylactic administration of rFVIIa is successful in reducing the number of bleeding events. This suggests that a single rFVIIa dose has a pro-haemostatic effect up to 24 hours (h), which is difficult to explain given its half-life of 2 h. In this study, six pigs received a 90 µg/kg rFVIIa bolus. Plasma was collected and platelets were isolated at various time points up to 48 h, and analysed for FVIIa levels and associated haemostatic activity. Elevated plasma FVIIa levels were detected up to 24 h post-administration (36 (32-56) mU/ml [median (interquartile range [IQR]), 24 h] vs 2 (2-14) mU/ml [baseline]). Corresponding prothrombin time (PT) values remained shortened compared to baseline until 24 h post-administration (9.4 (9.3-9.9) seconds (s) [24 h] vs 10.5 (10.2-11.0) s [baseline], p ≤0.01). The lag time in thrombin generation testing as well as clotting times in plasma-based assays were shortened up to 12 or 24 h post-administration, respectively (lag times 1.8 (1.7-2.1) minutes (min) [12 h] vs 2.3 (2.3-2.6) min [baseline], p ≤0.01 and clotting times 3.8 (3.2-3.9) min [24 h] vs 5.2 (4.6-5.5) min [baseline], p ≤0.001). Platelet FVIIa levels were elevated up to 48 h (7.7 (3.4-9.0) ng VIIa/mg actin [48 h] vs 2.5 (0.7-4.8) ng VIIa/mg actin [baseline]). In conclusion, elevated and haemostatically active plasma and platelet FVIIa levels are detectable up to 24-48 h following rFVIIa administration in pigs. This prolonged pro-haemostatic effect of FVIIa may explain the prophylactic efficacy of a once-daily rFVIIa treatment.
    Thrombosis and Haemostasis 04/2014; 112(2). · 5.76 Impact Factor
  • Joost C M Meijers
    Blood 03/2014; 123(11):1629. · 9.78 Impact Factor
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    ABSTRACT: BackgroundA common complication after aneurysmal subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI), which is associated with vasospasm and other mechanisms such as microthrombosis. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity plays a role in the prevention of thrombus formation in the cerebral microvasculature. Previously, we observed that patients with DCI have lower levels of ADAMTS13.Objectives To examine if recombinant human ADAMTS13 (rADAMTS13) reduces cerebral microthrombi formation and brain injury in an experimental mouse model of SAH including wildtype and ADAMTS13 -/- mice.Methods Experimental SAH was induced using the prechiasmatic blood injection model. The following experimental groups were investigated: 1) C57BL/6J mice (n=10); 2) C57BL/6J mice (n=10) treated with rADAMTS13 20 minutes after SAH; 3) ADAMTS13 -/- mice (n=10); and 4) ADAMTS13 -/- mice (n=10) treated with rADAMTS13 20 minutes after SAH. Mice were sacrificed at 48 hours. Results are presented as the mean with standard errors of the mean.ResultsInfusion with rADAMTS13 reduced the extent of microthrombosis with approximately 50% both in wildtype mice (mean fibrinogen area: 0.28±0.09% versus 0.15±0.04%; p=0.20) and ADAMTS13 -/- mice (mean fibrinogen area: 0.32±0.05% versus 0.16±0.03%; p=0.016). In addition, rADAMTS13 reduced brain injury with more than 60% both in wildtype mice (mean microglia area: 0.65±0.18% versus 0.18±0.04%; p=0.013) and ADAMTS13 -/- mice (mean microglia area: 1.24±0.36% versus 0.42±0.13%; p=0.077).Conclusions Our results support the further study of rADAMTS13 as a treatment option for the prevention of microthrombosis and brain injury after SAH.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 03/2014; · 6.08 Impact Factor
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    ABSTRACT: Pneumococcal pneumonia is a frequent cause of gram-positive sepsis and has a high mortality. The endothelial protein C receptor (EPCR) has been implicated in both the activation of protein C (PC) and the anti-inflammatory actions of activated (A)PC. The aim of this study was to determine the role of the EPCR in murine pneumococcal pneumonia and sepsis. Wild-type (WT), EPCR knockout (KO) and Tie2-EPCR mice, which overexpress EPCR on the endothelium, were infected intranasally (pneumonia) or intravenously (sepsis) with viable Streptococcus pneumoniae and euthanised at 24 or 48 hours after initiation of the infection for analyses. Pneumonia did not alter constitutive EPCR expression on pulmonary endothelium but was associated with an influx of EPCR positive neutrophils into lung tissue. In pneumococcal pneumonia EPCR KO mice demonstrated diminished bacterial growth in the lungs and dissemination to spleen and liver, reduced neutrophil recruitment to the lungs and a mitigated inflammatory response. Moreover, EPCR KO mice displayed enhanced activation of coagulation in the early phase of disease. Correspondingly, in pneumococcal sepsis EPCR KO mice showed reduced bacterial growth in lung and liver and attenuated cytokine release. Conversely, EPCR-overexpressing mice displayed higher bacterial outgrowth in lung, blood, spleen and liver in pneumococcal sepsis. In conclusion, EPCR impairs antibacterial defense in both pneumococcal pneumonia and sepsis, which is associated with an enhanced pro-inflammatory response.
    Thrombosis and Haemostasis 01/2014; 111(5). · 5.76 Impact Factor
  • Niraj Mishra, Joost C.M. Meijers, Paul J. Declerck, Ann Gils
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known. We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis. Thirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs. Addition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001). The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma. The anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis.
    PLoS ONE 01/2014; 9(2):e88390. · 3.53 Impact Factor
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    ABSTRACT: To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.
    PLoS ONE 01/2014; 9(6):e99890. · 3.53 Impact Factor
  • M G M Kok, J C M Meijers, S-J Pinto-Sietsma
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    ABSTRACT: The relation between coagulation and atherosclerosis has been extensively described, pointing towards a hypercoagulable state in patients with atherosclerosis, especially in young individuals. However, not all studies were conclusive. It is known that the metabolic syndrome (MetS), a risk factor for coronary artery disease (CAD), is related to a higher incidence of thrombo-embolic events. We hypothesised that individuals with CAD at a young age and MetS have an increased prothrombotic potential. It was the study objective to analyse the endogenous thrombin potential (ETP) and related thrombin generation parameters in patients with CAD before the age of 51 in men and 56 in women with and without MetS features and their healthy first-degree relatives. In this case-control study we included 118 CAD patients and 50 first-degree relatives (controls). Parameters of thrombin generation were obtained with calibrated automated thrombinography. An adjusted general linear model (GLM) showed a positive association between the peak thrombin levels and the presence of CAD at a young age. Based on the NCEP criteria we divided our patient group in CAD patients with and without MetS, and compared them to the controls without MetS. We showed that CAD patients with MetS have increased ETP levels, both in comparison with healthy first-degree relatives and with CAD patients without MetS. There were no differences in ETP between patients without MetS and healthy controls. In conclusion, this study shows that individuals with CAD at a young age and MetS features have an increased prothrombotic potential, compared to CAD patients without MetS.
    Thrombosis and Haemostasis 12/2013; 111(3). · 5.76 Impact Factor
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    ABSTRACT: Cerebrovascular complications are common in pneumococcal meningitis and are a main determinant of unfavourable outcome and death. We hypothesized that plasminogen activator inhibitor-1 (PAI-1) is a major contributor to cerebrovascular complications and death in pneumococcal meningitis. In a nationwide prospective cohort study we evaluated the effect of the 4G/5G polymorphism (rs1799889) in SERPINE1 (coding for PAI-1) on cerebrovascular complications and outcome in adults with pneumococcal meningitis proven by cerebrospinal fluid (CSF) culture. From 2006 to 2011, a total of 991 adult patients with community-acquired bacterial meningitis were included in the cohort and 712 had pneumococcal meningitis. The rs1799889 5G/5G genotype was associated with an increased risk of unfavourable outcome [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.03-2.78] and mortality (OR 2.20, 95 % CI 1.02-4.86) in white adults with pneumococcal meningitis. rs1799889 was associated with CSF PAI-1 concentrations (P = 0.048), and white patients homozygous for the low PAI-1 producing genotype (5G/5G) had a significantly higher risk for cerebral infarctions (P = 0.015) and haemorrhages (P = 0.005). Subsequently, we assessed the functionality of PAI-1 in a pneumococcal meningitis mouse model, using Serpine1 knockout mice. Consistent with the human data, Serpine1-deficient mice had increased mortality and cerebral haemorrhages compared to wild-type mice. We conclude PAI-1 is protective for death in humans and mice with pneumococcal meningitis by reducing cerebrovascular complications.
    Acta Neuropathologica 11/2013; · 9.73 Impact Factor
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    ABSTRACT: Cerebrovascular complications are common in pneumococcal meningitis and are a main determinant of unfavourable outcome and death. We hypothesized that plasminogen activator inhibitor-1 (PAI-1) is a major contributor to cerebrovascular complications and death in pneumococcal meningitis. In a nationwide prospective cohort study we evaluated the effect of the 4G/5G polymorphism (rs1799889) in SERPINE1 (coding for PAI-1) on cerebrovascular complications and outcome in adults with pneumococcal meningitis proven by cerebrospinal fluid (CSF) culture. From 2006 to 2011, a total of 991 adult patients with community-acquired bacterial meningitis were included in the cohort and 712 had pneumococcal meningitis. The rs1799889 5G/5G genotype was associated with an increased risk of unfavourable outcome [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.03-2.78] and mortality (OR 2.20, 95 % CI 1.02-4.86) in white adults with pneumococcal meningitis. rs1799889 was associated with CSF PAI-1 concentrations (P = 0.048), and white patients homozygous for the low PAI-1 producing genotype (5G/5G) had a significantly higher risk for cerebral infarctions (P = 0.015) and haemorrhages (P = 0.005). Subsequently, we assessed the functionality of PAI-1 in a pneumococcal meningitis mouse model, using Serpine1 knockout mice. Consistent with the human data, Serpine1-deficient mice had increased mortality and cerebral haemorrhages compared to wild-type mice. We conclude PAI-1 is protective for death in humans and mice with pneumococcal meningitis by reducing cerebrovascular complications.
    Acta Neuropathologica 11/2013; · 9.73 Impact Factor
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    ABSTRACT: The aggregation of amyloid β (Aβ) peptide is important in Alzheimer’s disease. Shorter Aβ fragments may reduce Aβ’s cytotoxicity and are used in diagnostics. The aggregation of Aβ16 is controversial; Liu et al. (J. Neurosci. Res. 75:162–171, 2004) and Liao et al. (FEBS Lett. 581:1161–1165, 2007) find that Aβ16 does not aggregate and reduces Aβ’s cytotoxicity, Du et al. (J. Alzheimer’s Dis. 27:401–413, 2011) reports that Aβ16 aggregates and that Aβ16 oligomers are toxic to cells. Here the aggregation potential of two shorter fragments, Aβ15 and Aβ16, and their influence on Aβ40 is measured by electron paramagnetic resonance (EPR) spectroscopy and the ThioT fluorescence assay (ThioT). Continuous-wave, 9 GHz EPR measurements and ThioT results reveal that neither Aβ15 nor Aβ16 aggregate by themselves and that they do not affect Aβ40 aggregation.
    Applied Magnetic Resonance 11/2013; · 0.83 Impact Factor
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    ABSTRACT: Numerous case reports have been published on acquired von Willebrand syndrome (aVWS) in patients with hypothyroidism, but no prospective studies have been published. The aim of this study was to investigate laboratory and clinical characteristics of aVWS in patients with newly diagnosed overt hypothyroidism. An observational cohort study was performed between May 2007 and February 2012. Consecutive hypothyroid patients before or within the first 48 h of replacement therapy were enrolled. At inclusion, blood was sampled for coagulation tests and bleeding history was documented by means of a standardized bleeding questionnaire. Repeat samples were obtained after restoration of euthyroidism. The prevalence of aVWS, defined as von Willebrand factor antigen (VWF:Ag) ≤50% and/or VWF ristocetin activity (VWF:RCo) ≤50%, was calculated. Patients with aVWS were subsequently divided into severe (VWF:Ag and/or VWF:RCo ≤10%), moderate (VWF:Ag and/or VWF:RCo between 10 and 30%) or mild (VWF:Ag and/or VWF:RCo between 30 and 50%). A total of 90 patients were included among whom a prevalence of aVWS of 33% was found. There were no patients with severe aVWS. Eight patients (9%) had moderate aVWS and 21 (23%) had mild aVWS. Bleeding score was negatively correlated with both VWF:Ag (β -0.32, P = 0.03) and VWF:RCo (β -0.32, P = 0.02). After restoration of euthyroidism, VWF:Ag had significantly increased by 44%, VWF:RCo by 36%, factor VIII by 39%, and endogenous thrombin potential by 10%. aVWS has a high prevalence in hypothyroid patients. Highest bleeding scores in patients with lower VWF levels suggest clinical relevance.
    Haemophilia 10/2013; · 3.17 Impact Factor
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    ABSTRACT: Carvedilol, a nonselective β-blocker, may be more effective than the selective β-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either β-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability. In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the β2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis. (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% ± 3.9% vs. 22.1% ± 2.8%, respectively, P = 0.003), irrespective of β2-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% ± 13% vs. 157% ± 13%, respectively, P = 0.01), irrespective of β2-adrenergic receptor haplotype. Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of β2-receptor haplotype status.
    Journal of Nuclear Medicine 08/2013; · 5.77 Impact Factor
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    ABSTRACT: Coagulation factor XI (FXI) is a promising target for anticoagulation, because of its major role in thrombosis and relatively minor role in haemostasis. This implies that inhibition of FXI can prevent thrombosis without causing bleeding. It was our aim to investigate the antithrombotic properties of two novel inhibitory anti-human FXI antibodies (αFXI-175 and αFXI-203). The in vitro properties of both antibodies were analysed using standard clotting assays and calibrated automated thrombography. For the in vivo model we used FXI knockout mice, in which FXI plasma levels were restored with purified human FXI. Thrombosis was induced by applying ferric chloride to the vena cava inferior, after which time to occlusion was analysed. A tail bleeding assay was used to investigate the safety of both antibodies. Using calibrated automated thrombography, both antibodies inhibited thrombin generation initiated via the intrinsic pathway. In contrast, upon tissue factor (TF)-initiated thrombin generation, αFXI-203 did not inhibit thrombin generation, while αFXI-175 inhibited thrombin generation only at low concentrations of TF. In the murine thrombosis model, the vena cava inferior remained patent for 25 minutes (min) in mice treated with αFXI-175 and for 12.5 min in αFXI-203 treated animals, which was significantly longer than in placebo-treated animals (5 min, p<0.05). Neither antibody caused severe blood loss in a tail bleeding assay. In conclusion, the two inhibitory antibodies against FXI prevented cessation of blood flow in a murine thrombosis model without inducing a bleeding tendency.
    Thrombosis and Haemostasis 08/2013; 110(4). · 5.76 Impact Factor
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    ABSTRACT: Renal transplant recipients are at increased risk of venous thromboembolic events, which is in part caused by their treatment with maintenance immunosuppressive drugs. Because we observed an increased incidence of venous thromboembolic events in renal transplant recipients treated with the mTOR inhibitor (mTORi) everolimus, we aimed to identify prothrombotic mechanisms of this immunosuppressive drug. In a single center study, nested in a multi-center randomized controlled trial, we measured parameters of coagulation, anti-coagulation and fibrinolysis in renal transplant recipients, receiving the mTORi everolimus (n=16, mTOR group) and compared them to a similar patient group, receiving a calcineurin inhibitor and/or mycophenolate sodium (n=20, non-mTOR group). All patients were at least 6months following transplantation with a stable transplant function. The use of an mTORi was associated with significantly higher levels of von Willebrand factor, prothrombin fragment 1+2, thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 as compared to a non-mTORi based immunosuppressive regimen. Treatment with an mTORi leads to increased endothelial activation, thrombin formation and impaired fibrinolysis in renal transplant recipients. This suggests an increased risk of thrombotic events in renal transplant recipients treated with mTOR inhibitors. A prospective study to establish the precise risk of thrombotic events in these patients is urgently needed.
    Thrombosis Research 07/2013; · 3.13 Impact Factor

Publication Stats

7k Citations
1,912.67 Total Impact Points

Institutions

  • 2006–2014
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2002–2014
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2000–2014
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Center for Infection and Immunity Amsterdam
      • • Department of Vascular Medicine
      • • Academic Medical Center
      • • Department of Cardiology and Cardio-thoracic Surgery
      Amsterdamo, North Holland, Netherlands
  • 2013
    • Universitair Medisch Centrum Groningen
      • Department of Surgery
      Groningen, Province of Groningen, Netherlands
    • University of Groningen
      • Department of Surgery
      Groningen, Province of Groningen, Netherlands
  • 1987–2011
    • University Medical Center Utrecht
      • • Department of Clinical Chemistry and Haematology
      • • Department of Hematology
      Utrecht, Utrecht, Netherlands
  • 2007–2009
    • Lund University
      • Department of Clinical Sciences
      Lund, Skane, Sweden
  • 2005–2009
    • Leiden University Medical Centre
      • • Department of Clinical Epidemiology
      • • Department of Hematology
      Leiden, South Holland, Netherlands
  • 2008
    • KU Leuven
      • Faculty of Pharmaceutical Sciences
      Leuven, VLG, Belgium
  • 1990–2006
    • University of Washington Seattle
      • • Department of Epidemiology
      • • Department of Biochemistry
      Seattle, WA, United States
  • 2004
    • Slotervaartziekenhuis
      Amsterdamo, North Holland, Netherlands
  • 1987–2002
    • Utrecht University
      • • Institute of Biomembranes
      • • Department of Hematology
      Utrecht, Utrecht, Netherlands
  • 2001
    • Slotervaart Ziekenhuis Amsterdam
      Amsterdamo, North Holland, Netherlands