title: Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients.
abstract: The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial-derived microparticles detected by high-sensitivity flow cytometry was investigated in 37 β-thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle-dependent tissue factor activity were evaluated. A high level of circulating erythrocyte- and platelet-microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non-splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid-dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra-microparticle labelling with anti-HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β-thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi-transfused β-thalassaemia major patients.
authors.affiliation: Centre de Référence Maladies Rares Thalassémies, Marseille-Lyon, Service d'Hémato-Oncologie Pédiatrique, Hôpital de la Timone, APHM, Marseille, France.
authors.forename: Imane
authors.initials: I
authors.lastname: Agouti
authors.affiliation: VRCM, INSERM UMR-S1076, UFR de Pharmacie, Université Aix Marseille, Marseille, France.|Service d'Hématologie et de Biologie Vasculaire, Hôpital de La Conception, AP-HM, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cointe
authors.affiliation: VRCM, INSERM UMR-S1076, UFR de Pharmacie, Université Aix Marseille, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Robert
authors.affiliation: RetT departement, Biocytex, Marseille, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Judicone
authors.affiliation: Unité d'Aide Méthodologique à la Recherche Clinique, AP-HM, Marseille, France.
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Département de Biochimie, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Fathi
authors.initials: F
authors.lastname: Driss
authors.affiliation: UMR-CBMN, University of Bordeaux-CNRS-IPB, Pessac, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Brisson
authors.affiliation: Service d'Hémato-Oncologie Pédiatrique, Hôpital d'Enfants, CHU de Nancy, Nancy, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Steschenko
authors.affiliation: Department d'Hématologie, Hôpital Saint Vincent de Paul, Lille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
authors.affiliation: Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarré
authors.affiliation: Service de Médecine Interne, Hôpital de la conception, AP-HM, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bernit
authors.affiliation: Centre de Référence Maladies Rares Thalassémies, Marseille-Lyon, Service d'Hémato-Oncologie Pédiatrique, Hôpital de la Timone, APHM, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: VRCM, INSERM UMR-S1076, UFR de Pharmacie, Université Aix Marseille, Marseille, France.|Service d'Hématologie et de Biologie Vasculaire, Hôpital de La Conception, AP-HM, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.affiliation: VRCM, INSERM UMR-S1076, UFR de Pharmacie, Université Aix Marseille, Marseille, France.|Service d'Hématologie et de Biologie Vasculaire, Hôpital de La Conception, AP-HM, Marseille, France.
authors.forename: Romaric
authors.initials: R
authors.lastname: Lacroix
authors.affiliation: Centre de Référence Maladies Rares Thalassémies, Marseille-Lyon, Service d'Hémato-Oncologie Pédiatrique, Hôpital de la Timone, APHM, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thuret
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D001803:Blood Transfusion; D055252:Cell-Derived Microparticles / Q000145:classification / Q000502:physiology*; D003131:Combined Modality Therapy; D003920:Diabetes Mellitus / Q000209:etiology; D004910:Erythrocyte Membrane / Q000648:ultrastructure; D005260:Female; D005319:Fetal Hemoglobin / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007006:Hypogonadism / Q000209:etiology; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000097:blood / Q000209:etiology; D008297:Male; D008563:Membrane Lipids / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000097:blood; D012306:Risk; D013156:Splenectomy; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology; D065227:Transfusion Reaction; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000150:complications / Q000601:surgery / Q000628:therapy
chemical_list: D001323:Autoantibodies; D008563:Membrane Lipids; D010718:Phosphatidylserines; D005319:Fetal Hemoglobin; D007501:Iron
keywords: erythrocytes derived-microparticles; platelets-derived microparticles; splenectomy; β-thalassaemia major