Publications by authors named "Birgit Frotscher"

12 Publications

  • Page 1 of 1

Outbreak of SARS-CoV-2: challenge for diagnosis and medical management in patients with left ventricular assist device: a case series.

Eur Heart J Case Rep 2021 Mar 7;5(3):ytaa447. Epub 2021 Mar 7.

Department of Cardiovascular Surgery and Transplantation, Regional Central Hospital of Lorraine University, Rue de Morvan, 54500 Nancy, France.

Background: The outbreak of coronavirus disease 2019 (COVID-19) exposes vulnerable patients to high risk of mortality. Patients with left ventricular assist device (LVAD) usually have symptoms such as cough, fever, and shortness of breath because of their cardiac condition and comorbidity, therefore these related symptoms challenge the correct diagnosis in time within the COVID-19 pandemic.

Case Summary: We report two case studies of patients with LVAD in whom COVID-19 related symptoms were overlapped by their cardiac status and comorbidities. In the first case, the patient was admitted for suspicion of COVID-19 due to cough and shortness of breath for 1 month. The blood test evocated a high index of suspicion of COVID-19. The nasopharyngeal test for COVID-19 performed on admission and at Day 2 was inconclusive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the test obtained on Day 3 of admission was positive, whereas computed tomography confirmed the diagnosis of COVID-19. This patient developed acute respiratory distress syndrome (ARDS) and nasal epistaxis within 48 h during hospitalization. The ARDS was treated by non-invasive ventilation and probabilistic antibiotics for 3 days and resulted significant improvement. The nasal epistaxis due to international normalized ratio increase was treated by nasal packing and vitamin K antagonist was switched to parenteral heparin infusion. The patient was kept hospitalized for 1 month for further supportive treatment. In the second case, the patient was admitted for recurrent anaemia due to melaena, the patient was tested for COVID-19 because of new-onset symptoms of cough and rhinorrhoea. The first nasopharyngeal test was positive, and sudden increase of anticoagulation status was noted in the setting of gastrointestinal bleeding. The anticoagulation status was controlled by parenteral heparin infusion, and the melaena was disappeared at Day 3. The moderate dyspnoea of the patient was quickly improved with nasal oxygen delivery for 4 days. The patient was discharged at Day 5.

Discussion: COVID-19 specific symptoms are challenging to distinguish in patients with LVADs, although radiological evidence can be beneficial in the COVID-19 diagnosis. We also observed the need for precise anticoagulation control to avoid bleeding or thrombotic events in these patients.
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http://dx.doi.org/10.1093/ehjcr/ytaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946800PMC
March 2021

The Hemarthrosis-Simulating Knee Model: A Useful Tool for Individualized Education in Patients with Hemophilia (GEFACET Study).

J Blood Med 2021 9;12:133-138. Epub 2021 Mar 9.

Haemophilia Treatment Centre, Hôpital Mignot, Versailles, France.

Background: Hemophilic arthropathy is a major complication in patients with severe hemophilia. A plastic knee model has been developed for the therapeutic education of patients to promote improved care management and self-treatment skills. The objective of this study was to evaluate the impact of this hemarthrosis-simulating artificial knee (HSAK) on patients' knowledge of their disease and its treatment.

Methods: In this observational study, the impact of HSAK was assessed during individualized education in patients with severe/moderately severe hemophilia A or B at seven hemophilia treatment centers in France. Participants provided written informed consent and completed questionnaires to assess knowledge of their disease (score range: 0-7) and knowledge of their treatment (score range: 0-4). Questionnaires were completed before, immediately after and 6 months after HSAK use. The scores obtained before and after the use of the HSAK were compared.

Results: The participants comprised 32 children, 29 teenagers, and 31 adults. The mean (SD) disease knowledge score increased significantly in all age groups of patients from 4.5 (2.0) to 5.9 (1.5; p<0.001) immediately after the training and remained unchanged at 6 months. Mean (SD) treatment knowledge scores were unchanged, but Wilcoxon signed rank testing showed a significant increase after the training course that was maintained at 6 months in children and teenagers.

Conclusion: These findings suggest that an individualized training course can enhance the understanding of hemophilia in patients of all ages, especially in children and teenagers, and that the HSAK may assist in improving patients' management of their disease.
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http://dx.doi.org/10.2147/JBM.S280032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955736PMC
March 2021

Effectiveness and safety of hFVIII/VWF concentrate (Voncento) in patients with inherited von Willebrand disease requiring surgical procedures: the OPALE multicentre observational study.

Blood Transfus 2021 Mar 27;19(2):152-157. Epub 2020 Nov 27.

Centre de Traitement de l'Hémophilie, CHU Hôtel-Dieu Nantes, Nantes, France.

Background: In patients with moderate to severe qualitative and quantitative von Willebrand disease (VWD), even minor surgical procedures can be associated with a risk of life-threatening bleeding. Treatment strategies vary according to the levels of von Willebrand factor (VWF) and Factor VIII (FVIII). The aim of this study was to evaluate the effectiveness and the safety of Voncento (CSL Behring, Marburg, Germany), a plasma-derived FVIII/VWF concentrate (ratio 1:2.4), during surgeries performed in patients with inherited VWD.

Materials And Methods: The OPALE study, a French multicentre observational study, was carried out from May 2016 to May 2019. It evaluated and analysed patients with inherited VWD (any type) requiring treatment with Voncento who underwent surgery.

Results: In total, 92 patients were enrolled, and 66 patients underwent 100 surgical procedures: 69 minor and 31 major surgeries conducted in 30 patients with type 1, 50 patients with type 2, and 20 patients with type 3 VWD. During minor surgeries, the median number of infusions was one (range: 1-9), the pre-operative loading dose was 41 IU VWF:RCo kg (range: 18-147), and the total dose was 63 (range: 18-594). During major surgeries, the number of infusions was 4 (range: 1-23), the pre-operative loading dose was 43 (range: 25-66) IU VWF: RCo kg, and the total dose was 155 (range: 40-575). The median FVIII:C levels ranged from 78 to 165 IU dL during 5 days after minor surgeries and from 86 and 167 IU dL during 11 days after major surgeries. VW:RCo levels ranged between 35 and 65 IU dL and between 34 and 76 IU dL after minor and major surgeries, respectively. The overall clinical effectiveness was qualified as "excellent" or "good" in 99% of patients. No thrombotic events related to Voncento were recorded.

Discussion: The present study suggests that Voncento is an effective and well-tolerated therapy for the peri-operative management of patients with all VWD types.
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http://dx.doi.org/10.2450/2020.0246-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925218PMC
March 2021

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

Pharmaceutics 2020 Apr 21;12(4). Epub 2020 Apr 21.

Department of Medical Pharmacology, University Hospital of Reims, EA3801, SFR Cap-Santé, University of Reims, 51100 Reims, France.

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.
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http://dx.doi.org/10.3390/pharmaceutics12040380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238177PMC
April 2020

FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders.

Eur J Epidemiol 2019 May 5;34(5):521-532. Epub 2018 Dec 5.

Haemophilia Treatment Centre, APHM, Children Hospital La Timone, Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.

FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3.8%) were reported by clinicians to have died and 159 (1.6%) to be lost to follow-up. Among the remaining 9504 patients still being followed up, 5748 (60.5%) had haemophilia A, 1300 (13.7%) haemophilia B, 1980 (20.8%) von Willebrand Disease while 476 (5.0%) had another clotting factor deficiency (Factor I, II, V, combined V and VIII, VII, X, XI and XIII). The median age of the population was 32 years (Inter-quartile range (IQR) 18-50 years) at data extraction on December 30th, 2016. The subgroup of children (i.e., < 18 years old) with severe haemophilia and comprehensive information available since the first exposure to treatment was identified as the PUPs (Previously Untreated Patients) cohort. Data for the 643 children included in the PUPs' cohort had been collected since their birth. Follow-up data were collected by the clinicians in haemophilia treatment centres (HTC) every 12.9 months on median (IQR 11.4-21.3). In the PUPS cohort, data were updated every 6.2 months on median (IQR 3.7-11.7). A unique patient number assigned at study inclusion was kept at individual HTC by participating clinicians. The data collected included demographic, clinical, therapeutic and biological items on standard electronic forms. As of December 30th 2016, a plasma and serum samples was available for 2581 patients (27.1%).
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http://dx.doi.org/10.1007/s10654-018-0468-7DOI Listing
May 2019

Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study.

BMJ Open 2018 07 25;8(7):e022409. Epub 2018 Jul 25.

Haemophilia Treatment Centre, Hospital Edouard Herriot, University Hospital of Lyon, Lyon, France.

Introduction: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.

Methods And Analysis: We present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14-17 years) with those from a group of young adults (aged 20-29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants' views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.

Ethics And Dissemination: The study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.

Trial Registration Number: NCT02866526; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-022409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067371PMC
July 2018

Usefulness of Flow Cytometric Mepacrine Uptake/Release Combined with CD63 Assay in Diagnosis of Patients with Suspected Platelet Dense Granule Disorder.

Semin Thromb Hemost 2016 Apr 12;42(3):282-91. Epub 2016 Feb 12.

Service d'Hématologie Biologique, CHRU Nancy, Nancy, France.

Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled. The flow cytometric assays were systematically performed to further investigate dense granule functionality. Among the 26 included patients, 18 cases showed impaired mepacrine uptake/release and reduced CD63 expression on activated platelets, consistent with δ-storage pool deficiency (SPD). Another seven patients showed decrease in mepacrine release and CD63 expression but mepacrine uptake was normal, indicating secretion defect rather than δ-SPD. Unfortunately, ATP secretion could not be measured in 7 out of the 26 patients due to insufficient sample and/or severe thrombocytopenia. This test combination provides a rapid and effective method to detect the heterogeneous abnormalities of platelet dense granule by distinguishing between storage and release defects. This combination is particularly advantageous for severely thrombocytopenic patients and pediatric patients in which only minimal sample is required.
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http://dx.doi.org/10.1055/s-0035-1564836DOI Listing
April 2016

Transfusion medicine illustrated. Blast cell fragments mimic platelets in acute monoblastic leukemia.

Transfusion 2015 Jun;55(6):1154

Plateforme de Cytométrie, University Hospital, Nancy, France.

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http://dx.doi.org/10.1111/trf.12889DOI Listing
June 2015

Report of a recurrent cerebral venous thrombosis in a young athlete.

BMC Neurol 2014 Sep 22;14:182. Epub 2014 Sep 22.

Department of Neurology, University Hospital of Nancy, Hopital Central, 29 avenue du Marechal de Lattre de Tassigny-CO n, Nancy Cedex, 34 54035, France.

Background: Reports of occurrence of deep vein thrombosis during intensive sport are scarce. While a few cases have been described in the cerebral territory, these are only in the context of traumatism or anabolic agent consumption. Thus, causality with exercise remains uncertain and the mechanisms hypothetic. We present the case of a young athlete who experienced two episodes of severe cerebral venous thromboses (CVT), both during intensive training, in the absence of any other known thrombogenic factor.

Case Presentation: A healthy 26-year-old man presented a thrombosis of the superior sagittal sinus during recent intensive training for a triathlon. Investigation at the time found no drug or anabolic steroid consumption, or any hematologic or coagulation disturbance. Anticoagulation therapy was initiated for 10 months with good outcome. One year later, soon after returning to intensive exercise, mainly running, the patient presented a thrombosis of the straight sinus complicated by bithalamic hyperintensities observed on T2 magnetic resonance imaging sequences. Anticoagulation treatment was reinitiated and led to repermeabilization of the cerebral vein and reversibility of thalamic abnormalities. Four months later, the patient was free of headache and had no cognitive impairment. He continues to practice intensive sport with vitamin K antagonist as preventive treatment.

Conclusion: This is the first case report of recurrent CVT in a context of intensive sport, without any other thrombogenic features, suggesting a causal link. Intensive exercise should be considered as a potential promoting factor of CVT and investigated during routine examination.
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http://dx.doi.org/10.1186/s12883-014-0182-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177419PMC
September 2014

Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStar and Innovance.

Thromb Haemost 2014 Oct 7;112(4):825-30. Epub 2014 Aug 7.

Dr. Marc Trossaërt, Centre Régional de Traitement de l'Hémophilie, 1 Place Alexis RICORDEAU, Centre Hospitalier Universitaire, 44093 Nantes Cedex 1, France, Tel.: +33 2 40 08 74 68, Fax: +33 2 40 08 42 59, E-mail:

The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
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http://dx.doi.org/10.1160/TH14-02-0108DOI Listing
October 2014

Multiple myeloma with unusual inclusions.

Br J Haematol 2009 Jan 18;144(1). Epub 2008 Oct 18.

Department of Haematobiology, CHU Nancy, Vandoeuvre-lès-Nancy, France.

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http://dx.doi.org/10.1111/j.1365-2141.2008.07291.xDOI Listing
January 2009

Inhibition of IgE production by the imidazoquinoline resiquimod in nonallergic and allergic donors.

J Invest Dermatol 2002 Nov;119(5):1059-64

Department of Dermatology and Allergy, Charité, Campus Virchow Klinikum, Humboldt Universität zu Berlin, Germany.

The aim of this study was to examine whether the immune modulator resiquimod, which belongs like imiquimod to the imidazoquinolines, is capable of influencing IgE synthesis. Peripheral blood mono-nuclear cells from normal donors and patients with atopic dermatitis and with seasonal allergic rhinitis were analyzed in the presence of resiquimod, anti-CD40+interleukin-4 stimulation for induction of IgE, and anti-CD40+interleukin-4 in the presence of resiquimod, respectively. Our data show that spontaneous IgE production was inhibited in the presence of resiquimod, which was strongest at 10 ng per ml in both groups of allergic patients. Inhibition of IgE production after anti-CD40+interleukin-4 stimulation in the presence of resiquimod (10 ng per ml) was comparable between all the groups. In normal donors median inhibition of IgE synthesis was 93%, in seasonal allergic rhinitis patients 77%, and in patients with atopic dermatitis 72%. In order to rule out antiproliferative effects of resiquimod, which might influence IgE production, we also studied proliferation of peripheral blood mononuclear cells from normal donors, which remained unchanged in the presence of resiquimod at 0.1-10 ng per ml but was inhibited at 100 or 1000 ng per ml. In search of possible mechanisms responsible for the observed inhibition of IgE production, we analyzed the expression and production of molecules that are known to modulate IgE production, namely CD23 and interferon-gamma. CD23 expression on B cells was lower in the presence of resiquimod (10 ng per ml) in anti-CD40+interleukin-4 stimulated cells, whereas interferon-gamma was strongly induced (4-6-fold) by resiquimod (10 ng per ml). Furthermore, by using neutralizing interferon-gamma monoclonal antibodies, we show that inhibition of IgE production occurred in an interferon-gamma-dependent manner. Taken together our results show that resiquimod is a potent modulator of IgE production in vitro in normal but also in allergic donors.
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http://dx.doi.org/10.1046/j.1523-1747.2002.19531.xDOI Listing
November 2002