C Rothschild

Centre Hospitalier Universitaire de Dijon, Dijon, Bourgogne, France

Are you C Rothschild?

Claim your profile

Publications (60)223.33 Total impact

  • J Mingo-Robinet · T Odent · C Elie · M-F Torchet · C Glorion · J-P Padovani · C Rothschild ·
    [Show abstract] [Hide abstract]
    ABSTRACT: In haemophiliacs, recurrent hemarthrosis and chronic synovitis lead to chronic arthropathy. Synovectomy is indicated when medical treatment fails. Few studies report the results of open synovectomy of the ankle in haemophiliacs with a small number of procedures and also a limited follow-up. The aim of this paper is to report the long-term results of open surgical synovectomy of the tibio-talar joint. Thirty-two open synovectomies were performed in 21 young haemophiliacs in the same haemophilia center using an antero-lateral and postero-medial approaches. The median follow-up was 15.4 years. Clinical (Petrini scores) and radiological evaluations (Pettersson scores) were made preoperatively and at each multidisciplinary follow-up visit. Wilcoxon and Spearman's tests were used for the statistical analysis. Preoperative median Petrini score was 6 (range 3-12), and improved at 2 and 5 years follow-up (P = 0.0003 and P = 0.0001 respectively). At 10 and 15 years follow-ups, median score remained below preoperative score (median 3.5, range 0-11). Ten ankles had a follow-up of more than 20 years. Preoperative median Petterson score presented a slight but continuous worsening in the first 2 and 5 years of follow-ups (P = 0.02, P = 0.003), but not correlation between clinical and radiological results was observed. Our long-term results support that clinical scores are improved even if radiological scores progress. Open synovectomy retards the progression of the arthropathy, but not stops it. Bleeding and pain are controlled and even if recurrence of bleedings is frequent, it is less severe, less painful and requiring less factors replacement. © 2015 John Wiley & Sons Ltd.
    Haemophilia 07/2015; 21(4):e306-11. DOI:10.1111/hae.12704 · 2.60 Impact Factor
  • Thierry Calvez · Hervé Chambost · Patrick Lutz · Chantal Rothschild · Jenny Goudemand ·

    Blood 06/2015; 125(24):3817-3819. DOI:10.1182/blood-2015-02-622167 · 10.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: EQOFIX is a medicoeconomic study that analyzed the health-related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma-derived Factor IX (pdFIX) or recombinant FIX (rFIX). The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX. In this observational study we included and followed for 1 year severe and moderate hemophilia B patients without inhibitor. HRQoL was evaluated through generic and disease-specific questionnaires. Information on the health resources consumed was collected every 3 months. The EQOFIX cohort was composed of 155 patients, including 51 children and 104 adults, with 114 having severe disease and 41 having moderate disease. The regimens were prophylactic for 61 and on demand for 94. Altogether, 78 were treated with rFIX and 77 with pdFIX. There was no difference in the QoL between the pdFIX and rFIX treatments. The extra cost of prophylaxis was €22,605 per bleeding event prevented. The consumption of FIX was 1.4-fold higher for the patients treated with rFIX than for the patients treated with pdFIX. Our findings in a cohort composed of 25% of the French population of moderate and severe hemophilia B patients show, with similar clinical and HRQoL results, that treatment with rFIX is more expensive than treatment with pdFIX. © 2015 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.
    Transfusion 02/2015; 55(7). DOI:10.1111/trf.13016 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study reports on 15 years of experience, in a single haemophilia care centre in France, with central venous access devices (VADs) in children with haemophilia. Following the insertion of a central VAD, patients were requested to return to the hospital on a quarterly basis for a multidisciplinary appointment which included clinical examination, chest X-ray, cardiac and major vessels ultrasound and preventive fibrinolysis. The family was urged to return to the Haemophilia Care Centre if complications or problems occurred. The follow-up comprised 50 patients. Data were collected prospectively. The total number of days with a VAD was 86 461 days and the total number of times the VAD was used was 41 192 (approximately every other day). Mean duration of VAD placement was 1269 days (range 113–2794 days). There were 25 complications, of which 9 haematomas and 5 systemic infections. Two VADs, infected with Staphylococcus aureus, had to be replaced. The infection rate was calculated as 0.0578 infections/1000 catheter days. There were no cases of thrombosis. This study concluded that most VAD infections in children can be avoided, even in patients requiring intense, prolonged treatment. The very low infection rate was achieved through the efforts of a multidisciplinary team, combined with extensive training for all individuals involved, adherence to written protocols and specific monitoring measures.
    Haemophilia 01/2015; 21(4). DOI:10.1111/hae.12638 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Haemophilia A (HA) is a congenital bleeding disorder resulting from factor VIII (FVIII) deficiency. The most serious complication of HA management is the appearance of inhibitory antibodies (Abs) against injected FVIII concentrates. To eradicate inhibitors, immune tolerance induction (ITI) is usually attempted, but it fails in up to 30% of cases. Currently, no undisputed predictive marker of ITI outcome is available to facilitate the clinical decision. This study aimed at identifying predictive markers of ITI efficacy. The isotypic and epitopic repertoires of inhibitory Abs were analysed in plasma samples collected before ITI start from 15 children with severe HA and high-titre inhibitors and their level compared in the two outcome groups ("ITI success": n=7, and "ITI failure": n=8). The predictive value of these candidate biomarkers and of the currently used indicators (inhibitor titre and age at ITI start, highest inhibitor titre before ITI and interval between inhibitor diagnosis and ITI start) was then compared by statistical analysis (Wilcoxon test and ROC analysis). While current indicators seemed to fail discriminating patients in the two outcome groups (ITI success or failure), anti-A1 and -A2 Abs levels before ITI start appeared to be good potential predictive markers of ITI outcome (p < 0.018). ROC analysis showed that anti-A1 and -A2 Abs were the best at discriminating between outcome groups (AUC > 0.875). Anti-A1 and -A2 Abs could represent new promising tools for the development of ITI outcome predictive tests for children with severe HA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 01/2015; 13(4). DOI:10.1111/jth.12846 · 5.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The choice of plasma-derived products (PdP) vs. recombinant products (RP) for treating haemophilia is influenced by the infectious and perceived safety of the products. Batch recall of PdP due to the risk of variant Creutzfeldt-Jakob disease (vCJD) may have unfavourable psychological impacts on haemophilia patients and influence their product preferences. This study aimed to assess the psychological impact of batch recalls of PdP in six haemophilia patients and their therapeutic demands, and to discuss the ethical problems in physicians’ management of this event. A survey was conducted using a new interview form and an existing anxiety and depression questionnaire. Batch recalls produce recurrent negative emotional outcomes in haemophiliacs and their families. The quality, understanding and efficiency of the batch recall announcements were unsatisfactory in some respects. Only one patient still had some of the vials in question, and only three patients understood the real reason for the batch recall. Four patients asked to change their PdP for RP; a fifth patient was considering doing so. Here, topics for discussion include the delivery of an unclear message to patients about a very uncertain risk of a frightening disease, the reasons to maintain PdP when RP are largely available, except in specific cases, and the related discomfort for caregivers. The ethical questions revealed by batch recalls and the high psychological impact of vCJD risk on patients can no longer be ignored, and require surveys assessing the rationales and choices of the healthcare authorities, manufacturers, prescribers and users.
    Haemophilia 01/2015; 21(1). DOI:10.1111/hae.12515 · 2.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In January 2013 the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a so-called second-generation full-length rFVIII (Product "D") in previously untreated patients (PUPs) with severe hemophilia A (HA). A prospective cohort was established by French public health authorities in 1994 to monitor hemophilia treatment safety. A PUP subgroup was specifically designed to investigate risk factors for inhibitor development. We analyzed our cohort dataset in view of the RODIN findings. After excluding 50 patients who also participated in the RODIN study, the primary analysis focused on 303 severe HA boys first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D versus the most widely used rFVIII product (adjusted-HR 1.55, 95%CI 0.97-2.49). Similar results were found for high-titer inhibitors and in ten sensitivity analyses. No heterogeneity was observed between RODIN and FranceCoag results. Combined aHRs were 1.58 (95%CI 1.17-2.14) for all inhibitors and 1.70 (95%CI 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D versus other rFVIII products in PUPs with severe HA.
    Blood 09/2014; 124(23). DOI:10.1182/blood-2014-07-586347 · 10.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Induction of heme oxygenase-1 (HO-1), a stress inducible enzyme with anti-inflammatory activity, reduces the immunogenicity of therapeutic factor VIII in experimental hemophilia A. In human, HO-1 expression is modulated by polymorphisms in the promoter of the HO-1-encoding gene (HMOX1). We investigated the relationship between polymorphisms in the HMOX1 promoter and factor VIII inhibitor development in severe hemophilia A. We performed a case-control study on 99 inhibitor-positive patients and 263 patients who did not develop inhibitor within the first 150 cumulative days of exposure to therapeutic factor VIII. Direct sequencing and DNA fragment analysis were used to study (GT)n polymorphism and single nucleotide polymorphisms located at 1135 and 413 in the promoter of HMOX1. We assessed associations between the individual allele frequencies or genotypes, and inhibitor development. Our results demonstrate a higher frequency in inhibitor-positive patients of alleles with large (GT)n repeats (L: n≥30), that are associated with a lesser HO-1 expression [odds ratio (OR) 2.31; 95% CI 1.46-3.66, p<0.001]. Six genotypes (L/L, L/M, L/S, M/M, M/S and S/S) of (GT)n repeats were identified (S: n<21; M: 21≤n<30). The genotype group including L alleles (L/L, L/M and L/S) was statistically more frequent among inhibitor-positive than inhibitor-negative patients, as compared to the other genotypes (33.3% versus 17.1%) [OR 2.21, 95% CI 1.30-3.76, p<0.01]. To our knowledge, this is the first association between HMOX1 promoter polymorphism and development of anti-drug antibodies. Our study paves the way towards modulation of the endogenous anti-inflammatory machinery of hemophilia patients to reduce the risk of inhibitor development.
    Haematologica 05/2013; 98(10). DOI:10.3324/haematol.2013.084665 · 5.81 Impact Factor
  • G E Rivard · C Rothschild · T Toll · K Achilles ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Immune tolerance induction (ITI) can overcome inhibitory factor VIII (FVIII) antibodies in haemophilia A patients receiving FVIII replacement therapy. The objective was to valuate the use of sucrose-formulated, full-length recombinant FVIII (rFVIII-FS) for ITI therapy. Patients (<8 years at ITI start) with severe haemophilia A and a peak inhibitor titre >5 Bethesda units (BU) who underwent ITI with any rFVIII-FS dose for ≥9 months (or until success) were eligible for this retrospective study. Efficacy analyses included descriptions of ITI treatment regimens and outcomes; ITI success was determined solely at the discretion of the investigator. Safety analyses included assessment of adverse events. Of 51 enrolled patients, 32 [high dose (≥85 IU kg(-1) day(-1) ), n = 21; low dose, n = 11] were eligible for analysis. ITI was successful in 69% (22/32) of patients (high dose, 66.7%; low dose, 72.7%) after a median of 1.4 years (range, 0.1-3.6 years). Influencing factors for ITI success were start of ITI <1 year after inhibitor detection and an inhibitor titre <10 BU at ITI start. All patients successfully tolerized with ITI continued to receive rFVIII-FS prophylaxis as maintenance therapy, with no inhibitor recurrence from the end of ITI until study enrolment. Use of rFVIII-FS for ITI was effective and well tolerated; success rates were similar to those in published studies.
    Haemophilia 03/2013; 19(3). DOI:10.1111/hae.12102 · 2.60 Impact Factor
  • Source

    Value in Health 11/2012; 15(7):A515-A516. DOI:10.1016/j.jval.2012.08.1763 · 3.28 Impact Factor
  • C Rothschild · R D'oiron · A Borel-Derlon · Y Gruel · R Navarro · C Negrier ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Immune tolerance induction (ITI) can eliminate factor VIII (FVIII) inhibitory antibodies that appear during FVIII replacement therapy. If first-line ITI fails, switching to a different FVIII concentrate, especially one containing von Willebrand factor (VWF), has been advocated. The objective of the study was to assess the efficacy and safety of Haemate(®) P, a plasma-derived FVIII concentrate containing high levels of VWF, as ITI in severe haemophilia A patients who had failed at least one prior ITI attempt with a different FVIII concentrate. In this multicentre, observational study, Haemate(®) P was administered at a starting dose of 83-308 IU kg(-1) day(-1) (1500-6000 IU day(-1) ). Efficacy was assessed by standard criteria (e.g. Bethesda titre, FVIII recovery and half-life), and bleeding characteristics. Nine patients from six haemophilia centres were treated with Haemate(®) P after failing one (n = 2), two (n = 5) or three (n = 2) prior ITI courses. The median time from inhibitor detection to Haemate(®) P treatment was 5.4 years. The median Haemate(®) P dose was 134 IU kg(-1) , and the median treatment duration 32 months. During median of 47 months of follow-up, complete response, partial response and treatment failure were observed in one, three and five patients respectively. Five patients experienced seven adverse events (AEs), including two serious AEs (sepsis). Haemate(®) P was discontinued due to an AE in one patient with a partial response. Haemate(®) P salvage ITI resulted in complete or partial tolerization in four of nine patients (44%) who had failed previous ITI attempts using different FVIII concentrates.
    Haemophilia 10/2012; 19(2). DOI:10.1111/hae.12018 · 2.60 Impact Factor
  • Source
    A Aouba · S Breton · A Harroche · D Sy-Bah · M-F Torchet · L Frenzel · D Lasne · J-P Padovani · T Odent · C Rothschild ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Obturator muscles haematoma are rarely reported. The most often reported cases are primary pyomyositis or posttraumatic haematomas occurring during pelvic fractures. We firstly report herein two cases of spontaneous obturator internus haematoma (OIH) in two haemophiliacs with inhibitor. Clinical data and imaging of two patients treated in our clinic are reported here according to previously defined criteria of OIH in posttraumatic situation. Both patients were children suffering from severe and moderate haemophilia A, respectively, with an inhibitor at the time of the event. The clinical feature was marked by an iliopelvic pain letting discussing hip haemarthrosis, appendicitis or iliopsoas haematoma. For both patients ultrasonography (US) failed to provide the diagnosis. Careful and repeated clinical examinations eventually lead to suspect obturator haematoma which was confirmed by abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI). Respectively, high dose of FVIII or rFVIIa regimen allowed a rapid control of the muscular bleeding in the low and high responder inhibitor patients. Spontaneous OIH may be added to the differential diagnosis of iliopelvic pain in severe forms of haemophilia. US still often performed at first in such case remains unhelpful; abdominopelvic CT or MRI should be performed to discriminate among different diagnoses, including OIH which stays probably undiagnosed.
    Haemophilia 08/2012; 19(1). DOI:10.1111/j.1365-2516.2012.02929.x · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD.
    Haemophilia 09/2011; 18(3):e158-63. DOI:10.1111/j.1365-2516.2011.02662.x · 2.60 Impact Factor
  • A Aouba · G Rey · G Pavillon · E Jougla · C Rothschild · M-F Torchet · L Guillevin · O Hermine ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Deaths occurring in the context of acquired haemophilia (AH) may be related to inter-connected causes and mechanisms including bleeding, specific or older patient co-morbidities or iatrogenic complications. However, their magnitude remains unknown. This study aimed to determine the respective weight and frequency of the various causes of death in AH. Multiple-cause analysis based on death certificates data is used in this purpose. Over a 10-year period (2000-2009), 121 deaths with AH as a cause were registered in France. All the deaths were of adults (extremes: 47 and 99 years; mean age: 80.7 years). The average number of causes per death certificate was 4.7. AH was the underlying cause of death (UCD) in 69.4% of the cases, and was more frequent in the older subjects. In contrast, before age of 75 years, AH was more often a contributing cause of death. No postpartum or obvious thromboembolism-related deaths were registered. Haemorrhagic shock was the most frequent direct cause of death (DCD), followed by infectious events, cardiac dysfunction, metabolic and nutritional disorders with muscle wasting and decubitus complications, and cancers (52.9%, 26.4%, 7.5%, 5.8% and 4.1%, respectively). However, when AH was not reported as an UCD, infections become the first DCD (32.4%) followed by bleeding events (16.2%). Best prophylactic and curative strategies for infections are particularly required to improve the prognosis in AH. Moreover, as several of its DCD correspond also to steroids side effects, best tolerated immunosuppressant regimen with steroid-sparing agents adjoining are particularly awaited in AH population.
    Haemophilia 09/2011; 18(3):339-44. DOI:10.1111/j.1365-2516.2011.02647.x · 2.60 Impact Factor
  • A. Aouba · G. Pavillon · E. Jougla · C. Rothschild · M.F. Torchet · L. Guillevin · O. Hermine ·

    La Revue de Médecine Interne 06/2011; 32:S51. DOI:10.1016/j.revmed.2011.03.032 · 1.07 Impact Factor
  • Source
    Virginie Rampal · T Odent · M F Torchet · C Rothschild · C Elie · C Glorion · J P Padovani ·
    [Show abstract] [Hide abstract]
    ABSTRACT: In haemophiliacs, synovectomy is indicated for recurrent joint bleedings, despite medical treatment. We report a series of 23 surgical synovectomies of the knee with a median follow-up of 8.8 years. The median age of patients at surgery was 13.5 years. Clinical and radiological evaluations were made according to the Petrini and the Pettersson scores, at 1 and 5 years after surgery, and at the last follow-up. Wilcoxon and Spearman's tests were used for the statistical analysis. The Petrini score improved at 1 and 5 years (P < 0.001). Nine patients have 20 years of follow-up and a stable result. In more than half of the knees, no episode of recurrent bleeding occurred. The effect of surgery on the range of motion (ROM) was moderate and mobilisation under anaesthesia did not improve it significantly. There was a progressive worsening of the radiological score, but no correlation between clinical and radiological score was noticed (ρ = 0.08, P = 0.77). Complete synovectomy gives good long-term results in term of bleeding recurrence and overall function.
    Journal of Children s Orthopaedics 02/2010; 4(1):33-7. DOI:10.1007/s11832-009-0229-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: During the last decades, long-term prophylaxis has become the gold standard for the treatment of children with severe haemophilia A or B. Prophylactic replacement regimens modify the natural history of the disease by aiming at the prevention of haemarthrosis, target joints and arthropathy. This treatment represents a constraint and an enhanced exposure to anti-haemophilic concentrates, which means potential increase of related risks and significant additional cost. The context of crisis of confidence due to the blood borne infections in the 1980s, may have delayed prophylaxis as an universal gold standard.In the early 2000s, the French group CoMETH proposed recommendations based on the review of the international experience. At first, specific guidelines of long-term prophylaxis were dedicated to children with severe haemophilia A or B, aged 3 years or less, with no history of target joint or arthropathy. The main concerns of this regimen consist in the early start and the escalating intensification of the treatment. In the French haemophilia care centres, the diffusion of these guidelines has apparently induced a significant turning point in therapeutic practices for haemophilia children. In 2006, more comprehensive recommendations were diffused to take into account all the children with severe haemophilia, whatever the bleeding history and joint status. The analysis of their impact, jointly with the National cohort "France Coag Network", will first assess the widespread implementation of the recommendations and the observance of the prophylactic regimen and identify factors associated to the compliance.
    Archives de Pédiatrie 12/2009; 16(12):1571-8. DOI:10.1016/j.arcped.2009.08.010 · 0.41 Impact Factor
  • A Aouba · E Dezamis · A Sermet · C Rothschild · O Hermine · D Lasne · M-F Torchet ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of inhibitors following factor VIII replacement therapy is a serious complication in severe inherited haemophilia. Whereas significant experience, notably in orthopaedic surgery, is now obtained with the use of bypassing agents in haemophilia with high-titre inhibitor, new surgical challenges might occur due to patients' increasing life expectancy. A 56-year-old severe haemophilia A patient with a high-titre inhibitor was diagnosed for probable right temporoparietal malignant glioneuronal tumour on cerebral magnetic resonance imaging (MRI) (4 cm x 3 cm cerebromeningeal tumour with perilesional oedema and transfalcial herniation) requiring total resection. Then recombinant activated FVII (rFVIIa) was chosen as the haemostatic agent: bolus of 270 microg kg(-1) every 2 h during the first 24 h, 180 microg kg(-1) every 3, 4 and 6 h, respectively, at days 2-3, from days 4-10 and finally from days 11-15. Tranexamic acid was associated. Pre- and postoperative courses were uneventful, the surgical procedure being assessed at optimal haemostatic condition without any unusual haemorrhage on MRI controls, diffuse intravascular coagulation criteria or thromboembolic event. Intensive rFVIIa therapy has shown to be safe and effective in this first reported neurosurgery about a malignant tumour exhibiting to a high-bleeding risk notably in haemophilia with high-titre inhibitor. The use of lower doses of rFVIIa might have been possible; however, in the absence of accurate test for monitoring rFVIIa therapy, the potentially life-threatening complications of this procedure required maximum haemostasis with high rFVIIa doses.
    Haemophilia 09/2009; 16(1):54-60. DOI:10.1111/j.1365-2516.2009.02089.x · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The development of anti-factor VIII (FVIII) antibodies (Abs), also called inhibitors, is currently one of the most serious complications arising during the treatment of hemophilia A patients. Improved prevention and eradication of these Abs remain a challenge both for clinicians and scientists. Numerous studies in the literature have reported on their epitope specificity, on their mechanism of FVIII inactivation, as well as on the methods used for their detection. In this review, we summarize the current knowledge on the nature (isotypes, kinetic properties), epitope properties, and mechanisms of action of anti-FVIII Abs. Furthermore, we present methods for detection and epitope characterization of anti-FVIII Abs with emphasis on the Luminex technique susceptible to facilitate the monitoring of changes in the epitope specificity of these Abs.
    Clinical Reviews in Allergy & Immunology 02/2009; 37(2):67-79. DOI:10.1007/s12016-009-8119-0 · 5.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inherited afibrinogenemia is a rare autosomal recessive disorder characterized by the absence or trace amounts of plasma fibrinogen inducing varying bleeding tendencies. Little is known about the pharmacokinetics of plasma-derived fibrinogen concentrates used in the treatment of afibrinogenemic patients. This open, prospective, multicenter study assessed the pharmacokinetic and pharmacodynamic profiles of FIBRINOGENE T1 (FGT1; LFB, Les Ulis, France), a human fibrinogen concentrate treated with three specific biological safety steps. Patients/methods: Five adult patients with congenital afibrinogenemia received a single infusion of 0.06 g kg(-1) of FGT1. Plasma samples drawn up to day 14 were assayed for fibrinogen antigen and activity and for coagulation parameters in a central laboratory. Fibrinogen antigen and activity were similar and highly correlated, with very low between-patient variability for pharmacokinetic parameters. Fibrinogen levels increased rapidly and significantly, with a mean plasma concentration of 1.39 g L(-1) being achieved 1 h after the end of the infusion, leading to almost complete in vivo recovery (94%). The mean half-life was 3.4 days, with slow linear elimination, and the distribution was mainly restricted to the vascular compartment. Coagulation parameters were normalized after the infusion and during the following 6-10 days. FGT1 was well tolerated overall. FGT1 behaves like natural functional fibrinogen, and its pharmacokinetic properties are in line with those expected from a fibrinogen concentrate. Our findings suggest that FGT1 can restore efficient hemostasis in afibrinogenemic patients, and predict good clinical efficacy.
    Journal of Thrombosis and Haemostasis 09/2008; 6(9):1494-9. DOI:10.1111/j.1538-7836.2008.03076.x · 5.72 Impact Factor

Publication Stats

1k Citations
223.33 Total Impact Points


  • 2015
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2014-2015
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2009-2011
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France
  • 2007
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      Lutetia Parisorum, Île-de-France, France