P de Moerloose

University of Geneva, Genève, Geneva, Switzerland

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Publications (346)1563.55 Total impact

  • A Casini · M Neerman-Arbez · R A Ariëns · P de Moerloose
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    ABSTRACT: Congenital dysfibrinogenemia is a qualitative congenital fibrinogen disorder characterized by normal antigen levels of a dysfunctional fibrinogen. Diagnosis is usually based on discrepancy between fibrinogen activity and antigen levels but could require more specialized techniques for the assessment of fibrinogen function due to some limitations in routine assays. Molecular abnormalities, frequently heterozygous missense mutations localized in exon 2 of FGA and exon 8 of FGG, lead to defects in one or more phases of fibrinogen to fibrin conversion, fibrin network formation and other important functions of fibrinogen. The clinical phenotype is highly heterogeneous, from no manifestations to bleeding and/or thrombotic events. Asymptomatic propositi and relatives with the predisposing genotype are at risk to develop adverse outcomes during the natural course of the disease. Correlations between genotype and phenotype have not yet been clearly established, with the exception of some abnormal fibrinogens that severely increase the risk of thrombosis. Functional analysis of polymerisation and fibrinolysis, structural studies of the fibrin network and viscoelastic properties of fibrin clot could help to predict the phenotype of congenital dysfibrinogenemia but have not yet been evaluated in detail. The management is essentially based on personal and familial history; however, even individuals still asymptomatic and without family history should be carefully assessed and monitored. Particular situations, such as pregnancy, delivery and surgery require a multidisciplinary approach. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 03/2015; 13(6). DOI:10.1111/jth.12916 · 5.55 Impact Factor
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    ABSTRACT: Background Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available.Patients and methodsEighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n=42) or standard care (no rhuFVIIa; n=42). The primary efficacy outcome measure was the reduction of the need of specific second-line therapies, such as interventional hemostatic procedures, of blood loss and of transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the five days following rhuFVIIa infusion.ResultsrhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared to controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference: 41%, range 18%-63%; relative risk RR: 0.56 (0.42-0.76),). The delivery mode (vaginal or caesarean section) did not affect the primary outcome. No death occurred. Blood loss failed to be measured and transfusion needs did not differ. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism.Conclusion This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need of specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 01/2015; 13(4). DOI:10.1111/jth.12844 · 5.55 Impact Factor
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    ABSTRACT: Fibrinogen storage disease (FSD) is characterized by hypofibrinogenemia and hepatic inclusions due to impaired release of mutant fibrinogen which accumulates and aggregates in the hepatocellular endoplasmic reticulum. Liver disease is variable. We studied a new Swiss family with fibrinogen Aguadilla. In order to understand the molecular peculiarity of FSD mutations, fibrinogen Aguadilla and the three other causative mutations, all located in the γD domain, were modelled. The proband is a Swiss girl aged 4 investigated because of fatigue and elevated liver enzymes. Protein structure models were prepared using the Swiss-PdbViewer and POV-Ray software. The proband was found to be heterozygous for fibrinogen Aguadilla: FGG Arg375Trp. Familial screening revealed that her mother and maternal grandmother were also affected and, in addition, respectively heterozygous and homozygous for the hereditary haemochromatosis mutation HFE C282Y. Models of backbone and side-chain interactions for fibrinogen Aguadilla in a 10-angstrom region revealed the loss of five H-bonds and the gain of one H-bond between structurally important amino acids. The structure predicted for fibrinogen Angers showed a novel helical structure in place of hole 'a' on the outer edge of γD likely to have a negative impact on fibrinogen assembly and secretion. The mechanism by which FSD mutations generate hepatic intracellular inclusions is still not clearly established although the promotion of aberrant intermolecular strand insertions is emerging as a likely cause. Reporting new cases is essential in the light of novel opportunities of treatment offered by increasing knowledge of the degradation pathway and autophagy. © 2015 John Wiley & Sons Ltd.
    Haemophilia 12/2014; DOI:10.1111/hae.12719 · 2.47 Impact Factor
  • A Lebreton · A Casini · R Alhayek · K L Kouteich · M Neerman-Arbez · P de Moerloose
    Haemophilia 12/2014; 21(1). DOI:10.1111/hae.12584 · 2.47 Impact Factor
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    ABSTRACT: Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined FVII/FX deficiency) belongs to the group of bleeding disorders in which both factors show reduced plasma activity. It may arise from coincidental inheritance of separate coagulation factor deficiencies or a common cause as large deletions comprising both gene loci. The F7 and F10 genes are located on the long arm of chromosome 13. Here, we describe 10 cases with combined FVII/FX deficiency representing both genetic mechanisms of occurrence. Genetic analyses included direct sequencing of the F7 and F10 genes and MLPA (multiplex ligation-dependent probe amplification) for detection of heterozygous large deletions. In four patients, the combined deficiency was due to a large deletion within the terminal end of chromosome 13. In the remaining six cases the deficiency resulted from coincidental inheritance of different genetic alterations affecting both genes independently. In most cases, the genetic defects were heterozygous, presenting with prolonged PT, normal aPTT and mild or no bleeding symptoms. Only in one case compound heterozygous mutations were detected in the F10, resulting in prolonged aPTT and a more severe bleeding phenotype. To avoid a misdiagnosis of combined FVII/FX deficiency, analyses of single factor activities have to be performed in all cases with prolonged PT even if aPTT is normal. Genetic analyses are substantial for correct prediction of an inheritance pattern and a proper genetic counselling.
    Haemophilia 12/2014; 21(3). DOI:10.1111/hae.12604 · 2.47 Impact Factor
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    ABSTRACT: We conducted a multicentre study of 101 subjects with Congenital Dysfibrinogenemia (CD) to characterize the incidence of hemorrhagic and thrombotic events as well as complications of pregnancy and surgery. At the time of diagnosis, 10.9% and 13.9% had experienced major bleeding and thrombotic events, respectively. During a mean follow-up of 8.8 years after CD diagnosis, the incidence of major bleeding and of thrombotic events was 2.5 and 18.7 per 1000 patient-years respectively, with estimated cumulative incidences at an age of 50 years of 19.2% and 30.1%. We identified 111 pregnancies with an overall incidence of spontaneous abortions and post-partum hemorrhage of 19.8% and 21.4%, respectively. The risk of post-partum hemorrhage was associated with a previously identified bleeding phenotype (OR 5.8; 95%CI 1.2-28.0). Among 137 surgical procedures analyzed, 9 (6.5%) were complicated by abnormal bleeding. Propositi versus relatives, sex, mutation hotspots, fibrinogen levels and activity:antigen ratios were not associated with the risk of thrombotic or bleeding outcomes. In conclusion, the results of our study, the largest in genotyped CD and the first including long term history, indicate that propositi with CD and their relatives carry not only a high risk of major bleeding, including post-partum hemorrhage, but also of thrombotic event.
    Blood 10/2014; 125(3). DOI:10.1182/blood-2014-06-582866 · 10.43 Impact Factor
  • Tess Marchetti · Philippe de Moerloose · Marie Cohen
    Placenta 09/2014; 35(9):A57. DOI:10.1016/j.placenta.2014.06.185 · 3.29 Impact Factor
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    ABSTRACT: Background The HemosIL AcuStar Antiphospholipid assay (Instrumentation Laboratory, Bedford, USA) is a fully automated assay using chemiluminescent technology for the detection of anticardiolipin and anti-β2GPI antibodies. This assay showed excellent agreement between results of different laboratories. The cut-off values to define positivity were calculated in 250 healthy blood bank donors but were associated with large confidence intervals (CI).Objective The objective of this study was to more precisely determine the cut-off values of the HemosIL AcuStar Antiphospholipid assay by increasing the number of healthy blood bank donors through a multicenter study and by applying a normalization procedure of the distribution of each antibody.Methods Five laboratories participated to this study allowing the inclusion of 626 samples. We used a Box-Cox power transformation method to normalize the distribution and calculate the 99th percentile and the corresponding 95%CI for each antibody.ResultsThe revised cut-off values were overall lower than those initially calculated with more stringent CI and yielded a 4.2%-increase of sensitivity with a 2.7% decrease of specificity regarding thrombotic events or obstetrical complications.Conclusions We provide refined cut-off values for the detection of anticardiolipin and anti-β2GPI antibodies with the HemosIL AcuStar Antiphospholipid assay that should be preferred for routine use.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 09/2014; 12(12). DOI:10.1111/jth.12732 · 5.55 Impact Factor
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    ABSTRACT: Introduction Point of care devices (POCT) are used for coagulation evaluation in adults. Reduced blood volumes and the direct use of whole blood allow studies when venous puncture is difficult, such as in newborns. Elimination of sample transport is attractive for use in emergencies and intensive care. Objective To prospectively compare neonatal coagulation parameters measured by the GEM®PCL POCT versus a central laboratory. Materials and Methods Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) were performed on whole cord blood (POCT) and plasma (central laboratory) collected from consecutive newborns at Geneva University Hospital. Agreement was assessed with a Bland & Altman plot and intra-class correlation coefficient (ICC) in 213 newborns cord blood; intra-assay variability (repeatability) was assessed using ICC and coefficient of variation (CV). Results 189 samples were available for the agreement analysis, 24 were excluded for technical problems. The 95% limits of agreements in the Bland & Altman plot ranged from -5.6 to 11.6 and from -39.6 to 11.6 seconds for the PT and aPTT, respectively. The ICC between the two methods was 0.28 (CI 95% 0.06 to 0.47) for PT and 0.20 (CI 95% -0.06 to 0.42) for aPTT. Repeatability (ICC) on the 43 eligible samples was 0.46 (CI 95% 0.19 to 0.67) for PT and 0.52 (CI 95% 0.26 to 0.71) for aPTT. The CV was 10.6% and 12% for PT and aPTT, respectively. Conclusions In newborn cord blood, PT and aPTT measurements with the GEM®PCL POCT had poor agreement with the central laboratory and poor repeatability.
    Thrombosis Research 08/2014; 134(2). DOI:10.1016/j.thromres.2014.05.024 · 2.43 Impact Factor
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    M. Shima · C. Hermans · P. de Moerloose
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    ABSTRACT: The primary major issue in haemophilia treatment remains the development of inhibitors. Recently two novel bypassing products have been developed. First, a humanized bispecific antibody against FIXa and FX, termed hBS23, was produced utilizing these two molecules placed into a spatially appropriate position to mimic FVIIIa, and recently this mimetic activity and the pharmacokinetics of the original antibody were improved by engineering the charge properties of the variable region within the immunoglobulin. Using the new antibody, termed ACE910, a phase 1 study in 64 Japanese and Caucasian healthy adults was performed and data from this trial suggested that the product had medically acceptable safety and tolerability profiles. The other new bypassing agent is named MC710, and consists of a mixture of plasma-derived FVIIa and FX. Preclinical studies using in vitro and in vivo haemophilia B inhibitor monkey models indicated that the haemostatic effects of FVIIa and FX were enhanced by simultaneous administration. Results from phase I and II clinical studies suggested that MC710 had equal or greater pharmacokinetic (PK), pharmacodynamic (PD), efficacy and safety profiles than conventional bypassing agents in the treatment of joint bleeding in haemophilia patients with inhibitors. Another significant current issue in this context is the increased medical cost of conventional treatment due to the higher consumption of concentrates. Biosimilar products may offer advantages in these circumstances and may offer a less expensive alternative. Regulatory issues, however, together with acceptability of biosimilar materials and reimbursement policies as well as supply and demand incentives remain to be considered. Rare bleeding disorders (RBDs) have attracted less attention from the pharmaceutical industry than haemophilia or von Willebrand disease due to the limited number of patients involved. Many cases of this type have been treated, therefore, using fresh frozen plasma (FFP) or prothrombin complex concentrates (PCCs) which carry serious risks of infections, allergic reactions and fluid overload. Several specific plasma-derived or recombinant products including fibrinogen, FVIIa, FXI and FXIII have now become available, however, and a phase III clinical study of recombinant FXIIIa has recently been completed demonstrating safety and efficacy of substances of this nature.
    Haemophilia 05/2014; 20(s4). DOI:10.1111/hae.12413 · 2.47 Impact Factor
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    ABSTRACT: Introduction Causative mutations leading to congenital quantitative fibrinogen are frequently clustered in FGA encoding the fibrinogen Aα-chain. Mutations of FGB encoding the Bβ-chain are less common and of interest since the Bβ chain is considered the rate-limiting factor in the hepatic production of the fibrinogen hexamer. Method Four novel FGB mutations were identified in two afibrinogenemic (one new-born and one 30 years old male) and hypofibrinogenemic (a 49 years old female) patient, with heterogeneous thrombotic and bleeding phenotype. The human fibrinogen beta chain precursor protein sequence (P02675) was obtained from the UniProt database. The resulting models were analysed in SwissPdbViewer 4.1 and POV-Ray 3.7. Results The FGB c.895 T > C p.Y299H (numbering from the initiator Met) and the FGB c.1415G > T p.G472V were predicted to be deleterious by SIFT analysis. The first replaces an uncharged aromatic amino acid side chain by a positively charged side chain modifying the balance in the distribution of hydrophobic and hydrophilic of the 10 Å neighbourhood residues. The second replaces one non-charged aliphatic side chain by another without any changes for the 10 Å surrounding region. The FGB c.352C > T p.Q118X leads to a severe premature termination codon and the FGB intron 4: IVS4-1G > C (c719-1G > C) leads to skipping of exon 5 or usage of a cryptic acceptor site located upstream or downstream of the normal site. Conclusions The continuous characterization of novel molecular defects responsible for fibrinogen deficiency combined with modelling of mutant proteins will continue to provide a better comprehension of the complexity of fibrinogen synthesis and physiology.
    Thrombosis Research 05/2014; 133(5). DOI:10.1016/j.thromres.2014.01.022 · 2.43 Impact Factor
  • P. Bolton‐Maggs · J. Goudemand · C. Hermans · M. Makris · P. de Moerloose
    Haemophilia 05/2014; 20(4). DOI:10.1111/hae.12457 · 2.47 Impact Factor
  • T. Marchetti · A. Ruffatti · C. Wuillemin · P. de Moerloose · M. Cohen
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    ABSTRACT: Background Obstetrical antiphospholipid syndrome (APS) is defined by pregnancy complications associated with antiphospholipid antibodies (aPL). The mechanisms of the pathogenic effects of aPL in pregnancy are poorly understood. Toll-like receptors (TLR) have been implicated previously in APS.Objectives The aims of our study were: 1) to determine aPL effects on trophoblastic cell fusion and differentiation, 2) to identify which TLR is involved in this process and 3) to evaluate the efficacy of hydroxychloroquine (HCQ) to counteract the effects of aPL.Methods BeWo cells are a model for trophoblast fusion and differentiation. Fusion index (FI) was assessed by immunocytochemistry; and biochemical differentiation by ELISA measuring β-human choronic gonadotropin (β-hCG) hormone secretion. We used three types of aPL to study their effect on cell fusion and differentiation: aPL derived from obstetrical APS patients, affinity purified and polyclonal rabbit anti-β2-glycoprotein-1 (anti-β2GP1) antibodies. Experiments on fusion were confirmed on primary cytotrophoblastic cells.ResultsAll types of aPL used decreased fusion index in BeWo and primary trophoblastic cells (respectively 64%, 52%, 41% for BeWo cells and 67%, 62% for primary cells) and anti-β2GP1 antibodies decreased hCG secretion in BeWo cells (41%). To block TLR4 antibodies or to abolish TLR4 cell surface expression restored fusion index in both cell types and hCG excretion in BeWo cells. HCQ treatment induced the same effect and decreased TLR4 mRNA (resp. 40%; 35%) and protein expressions (resp. 62%; 42%) in BeWo cells.Conclusion Anti-β2GP1 antibodies decrease trophoblastic differentiation via TLR4. This effect is restored by HCQ suggesting its therapeutic interest in APS pregnancies.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 03/2014; 12(6). DOI:10.1111/jth.12570 · 5.55 Impact Factor
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    ABSTRACT: The antiphospholipid antibody syndrome (APS) is an auto-immune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). We recently demonstrated that Toll-like receptor 2 (TLR2) and CD14 contribute to monocyte activation aPLA. To study the mechanisms of cell activation by aPLA leading to pro-coagulant and pro-inflammatory responses. For this study, we used purified antibodies from plasmas of ten different patients with APS and from healthy donors. We demonstrate that aPLA but not control IgG, colocalizes with TLR2 and TLR1 or TLR6 on human monocytes. Blocking antibodies to TLR2, TLR1 or TLR6, but not to TLR4 decreased TNF and Tissue Factor (TF) responses to aPLA. Pharmacological and siRNA approaches revealed the importance of the clathrin/dynamin-dependent endocytic pathway in cell activation by aPLA. In addition, soluble aPLA induced NF-kB activation, while bead-immobilized aPLA-beads, which cannot be internalized, were unable to activate NF-kB. Internalization of aPLA in monocytes and NF-kB activation was dependent on the presence of CD14. We show that TLR2 and its co-receptors, TLR1 and TLR6, contribute to the pathogenicity of aPLA, that aPLA are internalized via clathrin- and CD14-dependent endocytosis and that endocytosis is required for NF-kB activation. Our results contribute to a better understanding of the APS and provide a possible therapeutic approach. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 02/2014; DOI:10.1111/jth.12536 · 5.55 Impact Factor
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    ABSTRACT: Congenital dysfibrinogenemias are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional levels compared with the level of fibrinogen antigen. To date a large number of mutations have been identified in patients with dysfibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature alpha-chain) at the amino-terminal end of the fibrinogen alpha chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 12/2013; DOI:10.1097/MBC.0000000000000039 · 1.38 Impact Factor
  • Tess Marchetti · Marie Cohen · Jean-Christophe Gris · Philippe de Moerloose
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    ABSTRACT: Obstetrical antiphospholipid syndrome (APS) is defined by obstetrical complications and the presence of antiphospholipid antibodies (aPL). Although the incidence of APS is still poorly known, this thrombophilia is now recognized as one of the most common acquired causes of recurrent fetal loss. The diagnosis of APS during pregnancy can be challenging because of its various clinical features. Mothers with APS have an increased risk of thrombosis, thrombopenia, and specific pregnancy‑related complications such as preeclampsia, eclampsia, and hemolysis elevated liver enzyme and low‑platelet syndrome. aPL can also lead to recurrent, early miscarriages, stillbirths, and to intrauterine growth restriction. Clinicians should be aware of all these characteristics and a thorough differential diagnosis should be performed. Testing for aPL also requires skill due to the difficulty of standardization and interpretation of tests. To know when testing should be performed and when to repeat tests are still a matter of debate. While general management and first‑line treatment of APS during pregnancy now have clear guidelines, second‑line treatment is still required in 30% of the cases and new strategies are currently in development. In this review, we describe the clinical and biological aspects of obstetrical APS and its current management options. As APS pregnancies can be a real challenge for clinicians, we underline the necessity of multidisciplinary counselling and close follow‑up.
    Polskie archiwum medycyny wewnȩtrznej 12/2013; 123(12):713-20. · 2.05 Impact Factor
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    ABSTRACT: Localization of Toll-like receptors (TLR) in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.
    PLoS ONE 12/2013; 8(12):e80743. DOI:10.1371/journal.pone.0080743 · 3.23 Impact Factor
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    Karim J Brandt · Egbert K O Kruithof · Philippe de Moerloose
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    ABSTRACT: The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effects of aPLA. Members of the TLR family and the platelet receptor apolipoprotein E receptor 2' (apoER2'), a receptor belonging to the low-density lipoprotein receptor (LDL-R) family, as well as GPIbα, were identified as putative candidates for aPLA recognition. CD14, a co-receptor for TLR2 and TLR4, and annexin A2, a ubiquitous Ca2(+)-binding protein that is essential for actin-dependent vesicle transport, could serve as important accessory molecules in mediating the pathogenic effects of aPLA. Finally, complement activation has been reported in association with the pathogenicity of APS. The relative contribution of these different mechanisms in the pathogenesis of APS is controversial. Here, we review the various in vivo and in vitro models that have been used to investigate the pathogenic mechanisms of aPLA in APS.
    Thrombosis Research 08/2013; 132. DOI:10.1016/j.thromres.2013.08.015 · 2.43 Impact Factor
  • C Hermans · P de Moerloose · G Dolan
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    ABSTRACT: Life expectancy for people with haemophilia (PWH) has improved and is now approaching that of the general population. The growing population of elderly PWH will therefore increasingly face the age-related morbidities such as cardiovascular diseases, malignant disease, liver disease, and bone and joint related diseases, as well as the lifestyle and psychosocial factors that accompany many of these conditions. For many PWH, frequent contact with haemophilia specialists within the comprehensive care centres supplants the relationship that individuals in the general population have with their general practitioners. As a result, there is a risk that elderly PWH may miss the chronic disease screening opportunities offered to the general population. This review focuses on the screening tests and examinations recommended for age-related comorbidities in the general population that may be applicable to the growing population of older people with haemophilia.
    Critical reviews in oncology/hematology 08/2013; DOI:10.1016/j.critrevonc.2013.07.005 · 4.05 Impact Factor
  • C Biron-Andreani · P de Moerloose · R D'oiron · H Chambost · J-F Schved · C Hermans
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    ABSTRACT: Lymphomas or hepatocarcinomas related to blood-borne transmitted diseases are well-known malignancies in persons with haemophilia (PWH). However, rising life expectancy has increased the number of PWH suffering from other malignancies. This study aimed to collect cancer occurrence data in PWH followed in five European haemophilia treatment centres (Brussels, Geneva, Marseille, Montpellier and Paris-Bicêtre) over the last 10 years and to analyse some particular features of cancer occurring in PWH. In total, 45 malignancies were diagnosed in 1067 PWH. The most common malignancies were hepatocellular carcinoma (12/45) and urogenital tract tumours (9/45). Bleeding at presentation or changes in bleeding pattern was indicative of cancer in four patients. Three patients with mild haemophilia developed anti-factor VIII inhibitors after intensive substitution therapy prior to surgery or invasive procedures. There was no bleeding associated with chemotherapy or radiotherapy. A few bleeding complications occurred following invasive (3/39) or surgical procedures (2/27) as a result of insufficient hemostatic coverage or in spite of adequate substitution. No bleeding was noted after liver or prostate biopsies. Following cancer diagnosis, five patients were switched from on-demand to prolonged prophylaxis substitution. In the majority of cases, the standard cancer treatment protocol was not modified on account of concomitant haemophilia. Thus, oncological treatments are not contraindicated and should not be withheld in PWH assuming that adequate haemostasis correction is undertaken. As shown by our study results, a change in bleeding pattern in adult PWH should raise suspicion of a malignancy. Intensive substitution must be considered a risk factor for inhibitor development.
    Haemophilia 08/2013; 20(1). DOI:10.1111/hae.12250 · 2.47 Impact Factor

Publication Stats

8k Citations
1,563.55 Total Impact Points

Institutions

  • 1991–2015
    • University of Geneva
      • • Division of Angiology and Hemostasis
      • • Department of Internal Medicine
      • • Division of Radio-oncology
      Genève, Geneva, Switzerland
  • 2000–2013
    • Hôpitaux Universitaires de Genève
      • • Service d'anesthésiologie
      • • Unité d'hémostase
      • • Service d'angiologie et d'hémostase
      Genève, GE, Switzerland
  • 2010
    • Hackensack University Medical Center
      Хакенсак, New Jersey, United States
  • 2005
    • The Ottawa Hospital
      Ottawa, Ontario, Canada
  • 2004
    • Spedali Civili di Brescia
      Brescia, Lombardy, Italy
  • 2002
    • Ospedale Regionale di Mendrisio
      Mendrisio, Ticino, Switzerland
  • 2001
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      Lutetia Parisorum, Île-de-France, France
  • 1990–2000
    • Cantonal Hospital of Schwyz
      Schwyz, Schwyz, Switzerland
  • 1993
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland