Jean-Pierre Cazenave

• MD, PhD
• Professor at University of Strasbourg

Background Auto‐immune thrombotic thrombocytopenic purpura (TTP) is a morbid multi‐organ disorder. Cardiac involvement not recognized in initial disease descriptions is a major cause of morbidity. Therapeutic plasma exchange (TPE) requires exposure to multiple plasma donors with risk of transfusion‐transmitted infection (TTI). Pathogen inactivation...

Introduction Des procédés pour inactivation des pathogènes dans les concentrés de globules rouges (CGR) tel qu’Intercept™ Blood System (IBS), ou dans le sang total générant ensuite un CGR tel que Mirasol™ sont en développement. Dans le cadre d’études in vitro et d’études cliniques, des CGR traités ont ainsi été produits. À L’EFS Grand-Est, la techn...

Background: The INTERCEPT Blood System (IBS) using amotosalen-HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma prot...

Aims: this study aimed to: – Analyze the HIV residual risk of transfusion at the cNts of Lomé from January 2008 to December 2012 – Indicate future directions to strengthen blood safety. Methods: the residual risk of HIV transmission by blood transfusion has been estimated by the indirect method proposed by scHrEIbEr. this method estimates the risk...

Objectifs Les objectifs sont : – d’analyser le risque résiduel transfusionnel du VIH au CNTS de Lomé (Togo) ; – de proposer les orientations futures pour renforcer la sécurité transfusionnelle. Méthodologie Le risque résiduel a été estimé chez des donneurs de sang total, bénévoles et réguliers par la méthode indirecte de SCHREIBER qui estimait le...

Liver transplant may require large-volume plasma transfusion with increased risk of transfusion-transmitted infection (TTI). Pathogen inactivation of plasma with amotosalen-UVA offers the potential to mitigate TTI risk. A retrospective cohort design was used to compare the therapeutic efficacy and key safety outcomes for liver transplants supported...

Platelets (PLTs) are currently stored at room temperature (RT) for 5 to 7 days. So far, there exists no validated method for the preparation and long-term storage of dehydrated PLTs suitable for transfusion after rehydration. In this study, a desiccation process, zeodration, was applied to PLTs. A complete procedure of dehydration at RT by zeodrati...

The present invention relates to a new method for the preservation of blood platelets. In particular, the present invention provides a method which includes submitting the platelets to zeodration carried out at temperatures between 18° C. and 24° C. The dried platelets thus obtained can be preserved at room temperature for long period of time. The...

This paper brings together the abstracts and proceedings of a seminar held on the topic of "ethics and transfusion", October 15, 2013 at the National Institute of Blood Transfusion, Paris. Copyright © 2014. Published by Elsevier SAS.

R. N. I. Pietersz, H. W. Reesink, S. Panzer, S. Oknaian, S. Kuperman, C. Gabriel, A. Rapaille, M. Lambermont, V. Deneys,D. Sondag, S. Ramirez-Arcos, M. Goldman, G. Delage, F. Bernier, M. Germain, T. Vuk, J. Georgsen, P. Morel, C. Naegelen,L. Bardiaux, J.-P. Cazenave, J. Dreier, T. Vollmer, C. Knabbe, E. Seifried, K. Hourfar, C. K. Lin, M. Spreafico,...

Pathogen inactivation (PI) of platelet concentrates (PCs) reduces the proliferation/replication of a large range of bacteria, viruses, and parasites as well as residual leucocytes. Pathogen-inactivated PCs were evaluated in various clinical trials showing their efficacy and safety. Today, there is some debate over the hemostatic activity of treated...

This paper brings together the abstracts and proceedings of a seminar held on the topic of “ethics and transfusion”, October 15, 2013 at the National Institute of Blood Transfusion, Paris.

Background Acquired auto-immune TTP due to ADAMTS13 deficiency is a rare microangiopathy (∼ 4 /106 persons/yr). Untreated, mortality is > 90%, but with therapeutic plasma exchange (TPE) remission rates are ∼ 80%, and mortality is < 20%. TPE requires large volumes of fresh frozen plasma (FFP) with risk of transfusion-transmitted infection (TTI). Pat...

Differentiation and maturation of megakaryocytes occur in close association with cellular and extracellular components in the bone marrow. Thus, direct examination of these processes in the native environment provides important information regarding the development of megakaryocytes. In this chapter, we present methods applied to mouse bone marrow...

Background: Platelet concentrate (PC) functionality decreases during storage. This is referred to as the storage lesion. Pathogen inactivation may accelerate or induce lesions, potentially accounting for reduced viability. Our aim was to characterize functional and biochemical properties of platelets (PLTs) from photochemically treated buffy-coat...

Phospholipid (PL) compositions and fatty acid (FA) patterns of PL were determined in the erythrocytes and blood thrombocytes of a seabird, the king penguin, living in the subantarctic area and feeding on prey rich in n−3 polyunsaturated FA. Results were compared between birds in three different physiological states (breeding and molting adults, chi...

The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly pol...

The transfusion of platelet concentrates is increasing in oncohematology patients due to chemotherapy and hematopoietic stem cell grafts. The transmission of pathogenic agents, viruses, parasites and especially bacteria with platelet concentrates stored at room temperature (20–24°C) is associated with a septic risk, partly prevented by bacterial de...

The transfusion of platelet concentrates is increasing in oncohematology patients due to chemotherapy and hematopoietic stem cell grafts. The transmission of pathogenic agents, viruses, parasites and especially bacteria with platelet concentrates stored at room temperature (20-24°C) is associated with a septic risk, partly prevented by bacterial de...

Atherosclerosis is an inflammatory disease, and extracellular nucleotides are one of the factors possibly involved in vascular inflammation. The P2Y(1) receptor for adenosine 5'-diphosphate has been shown to be involved in the development of atherosclerosis in apolipoprotein E--deficient mice. Our aim is to determine whether the endothelial P2Y(1)...

EP224283 combines in a single molecule idraparinux and tirofiban, which allows obtaining a predictable and sustained antiplatelet effect through the transfer of the pharmacokinetics properties of idraparinux to the anti-αIIbβ3 antagonist. The activity can be instantaneously neutralized by injection of avidin, a specific antidote. We have tested the...

The plasma membrane proteins CD1a, CD1b and CD1c are expressed by human dendritic cells, the professional antigen-presenting cells of the immune system, and present lipid antigens to T lymphocytes. CD1e belongs to the same family of molecules, but accumulates as a membrane-associated form in the Golgi compartments of immature dendritic cells and as...

The transfusion of labile blood products is vital and essential for patients in absence of alternative treatment. Patients and doctors have always feared transfusion-transmitted infections by blood, blood components and blood-derived drugs. Photochemical inactivation of platelet concentrates and plasma, using a technique associating amotosalen and...

The FeCl(3)-induced vascular injury model is widely used to study thrombogenesis in vivo, but the processes leading to vascular injury and thrombosis are poorly defined. The aim of our study was to better characterize the mechanisms of FeCl(3)-induced vascular injury and thrombus formation, in order to evaluate the pathophysiological relevance of t...

The transfusion of labile blood products is vital and essential for patients in absence of alternative treatment. Patients and doctors have always feared transfusion-transmitted infections by blood, blood components and blood-derived drugs. Photochemical inactivation of platelet concentrates and plasma, using a technique associating amotosalen and...

The Etablissement Français du Sang Alsace (EFS Alsace) successively implemented universal use of platelet additive solutions (PASs) and pathogen inactivation (PI) for platelet components (PCs). To assess the impact of these changes, EFS Alsace evaluated PC use, red blood cell (RBC) component use, and transfusion-related adverse events after impleme...

Transfusion of labile blood products (red cell concentrates, platelet concentrates and plasma) is vital in the absence of alternatives. Patients and doctors have always feared infections transmitted by blood, blood components and blood-derived drugs. It is potentially dangerous to delay implementation of pathogen inactivation in labile blood produc...

BACKGROUND: Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI1hour) as the primary outcome. STUDY DE...

Immature dendritic cells (DCs) patrol the circulation, where they can uptake antigens. It has been reported that mature monocyte-derived DCs have the ability to interact with an activated platelet monolayer under high shear conditions (1500s(-1) ). In this study, we investigated whether platelets can recruit immature myeloid DCs (CD1c(+) ) directly...

 Inactivation of the mouse Myh9 gene (Myh9Δ) or its mutation in MYH9-related diseases leads to macrothrombocytopenia. Paradoxically, previous studies using in vitro differentiated megakaryocytes showed an increased capacity for proplatelet formation when myosin was absent or inhibited.  To explore the origin of the thrombocytopenia induced by myosi...

A 56 year-old, multiparous woman suffering from a myeloproliferative syndrome, who had received multiple red blood cell and platelet transfusions, was the recipient of an allograft of peripheral blood stem cells derived from her HLA-A, B, DR, DQ and DP and ABO identical sister, following myeloablative conditioning. The persistence of severe, isolat...

Photochemical pathogen inactivation treatment (PCT) of plasma components with amotosalen and UVA has been implemented in Europe. To establish a postapproval safety database, an active hemovigilance (HV) program utilizing an electronic data capture system (EDCS) was initiated. The response to transfusion was documented after each PCT-plasma transfus...

It is likely that transmission of variant Creutzfeldt-Jakob disease (vCJD) occurs by transfusion and that the candidate infectious agent (PrP(TSE)) is present in small concentrations in the blood of infected donors in the asymptomatic phase of the disease. A new blood screening assay has been developed to detect PrP(TSE) in citrated plasma samples....

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blo...

The CYP2C19*2 genetic variant is known to contribute to low responsiveness to clopidogrel treatment, leading to a higher rate of cardiovascular events. Systematic identification of the 2C19*2 carriers to predict the individual patient's response to clopidogrel is a matter of debate. Data of the VASP-02 study comparing patients’ responsiveness to 75...

Targeting platelet activating components preferentially expressed in atherosclerotic plaques could represent an attractive anti-thrombotic strategy. Tenascin-C (TN-C) is an interesting candidate due to its high level of expression in atherosclerotic plaques while it is absent from healthy vessels. The aim of our study was to evaluate the capacity o...

Arterial thrombosis results from combined platelet activation and coagulation at sites of vascular injury. In acute ischemic events, the cornerstone of treatment is the association of antiplatelet drugs with anticoagulants. Here we investigated the effects of EP224283, a molecule combining antithrombin-dependent factor Xa (FXa) and GPIIb-IIIa inhib...

We previously described a model of laser-induced thrombosis in mesenteric arterioles with superficial and deep levels of injury producing a transient thrombus resolving within 2 min and a larger almost occlusive thrombus, respectively. Both types of lesion were sensitive to platelet GPIIb-IIIa and P2Y(12) inhibition, whereas only deep injuries were...

Circulating platelets are initially recruited at the site of vessel injury by von Willebrand factor (VWF) immobilized on collagen fibers. This process, mediated by the GPIb-V-IX complex, is accompanied by specific intracellular signaling leading to reorganization of the platelet actin cytoskeleton and extension of filopodia. To evaluate the GPIbalp...

Human Fcγ receptor type II (FcγRII/CD32) can be produced in a soluble form, termed FcγRIIa2, which contains the extra- and intracellular regions of the receptor, due to an alternative splicing of the transmembrane domain-encoding exon. We show that human sera contain two forms of FcγRIIa2. A full-length secreted protein, which has a 32 kDa backbone...

We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insuli...

The techniques for inactivation of pathogens in labile blood products (LBP) would appear to be the new strategy which will permit us to increase transfusion safety in the face of the risks of transmission of pathogenic agents by LBP. Various methods are in the course of development or already validated and used in France. The latter only apply howe...

Giant platelets and thrombocytopenia are invariable defects in the Bernard-Soulier syndrome caused by deficiency of the GPIb-V-IX complex, a receptor for von Willebrand factor supporting platelet adhesion to the damaged arterial wall. Various properties of this receptor may be considered potential determinants of the macrothrombocytopenia. To explo...

The techniques for inactivation of pathogens in labile blood products (LBP) would appear to be the new strategy which will permit us to increase transfusion safety in the face of the risks of transmission of pathogenic agents by LBP. Various methods are in the course of development or already validated and used in France. The latter only apply howe...

The monoclonal antibodies (mAbs) ALMA.17 and ALMA.7 recognize human platelet membrane proteins. ALMA.17 is directed against alpha(IIb)beta(3) integrin, but the target of ALMA.7 was unknown previously. Tandem Biacore micropurification and mass spectrometry (MS) analysis of a platelet membrane lysate was used to identify the target of ALMA.7. Deterge...

CD1e displays unique features in comparison with other CD1 proteins. CD1e accumulates in Golgi compartments of immature dendritic cells and is transported directly to lysosomes, where it is cleaved into a soluble form. In these latter compartments, CD1e participates in the processing of glycolipid antigens. In the present study, we show that the N-...

During the Chikungunya virus (CHIKV) epidemic on Ile de La Réunion, France, more than 30% of 750,000 inhabitants were infected. Local blood donation was suspended to prevent transfusion-transmitted infection (TT-CHIKV). To sustain the availability of platelet (PLT) components, the Etablissement Français du Sang implemented universal pathogen inacti...

Plasmatic soluble GPV (sGPV) is a novel bivalent activation marker with a potential to monitor platelet activation by thrombin in arterial and venous thrombosis. sGPV was found to be increased in several arterial thrombotic diseases including stroke and myocardial infarction. In a first study we tested its utility to grade acute coronary syndrome (...

Mutations in the MYH9 gene encoding nonmuscle myosin IIA lead to macrothrombocytopenia as observed in MYH9-related disorders. We used mice with megakaryocyte-restricted MYH9 inactivation to explore the role of myosin in thrombopoiesis. In situ, bone marrow MYH9Delta megakaryocytes were irregularly shaped, appearing leaky with poorly defined limits....

We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day. Patients show interindividual variability in their platelet response to clopidogrel. Low respo...

Background: Photochemical treatment (PCT) using amotosalen HCl and UVA light (3 J/cm2: 320 – 400 nm) inactivates pathogens and leukocytes in therapeutic single donor apheresis plasma prepared within 8 hr of collection (INTERCEPTTM [I-FFP], Cerus Europe, Amersfoort, Netherlands). Clinical trials demonstrated efficacy and safety supporting a Class II...

Blood transfusion is a critical supportive therapy for health care. The demand for platelet components (PCs), either derived from apheresis or from whole blood buffy coats, has continually increased as health care technology and life expectancy have increased. The public and the medical community expect that PCs for transfusion will be safe and ava...

The P2Y(1) receptor plays a key role in arterial thrombosis and is widely expressed in many cell types involved in atherosclerosis. The aim of this study was to evaluate its potential involvement in the development of atherosclerotic lesions. Apolipoprotein E-deficient (ApoE(-/-)) and P2Y(1)(-/-)/ApoE(-/-) mice were maintained on regular chow for 1...