title: Addition of in-vitro generated endothelial microparticles to von-Willebrand plasma improves primary and secondary hemostasis.
abstract: Increased endothelial microparticles (EMP) as markers for endothelial activation have been associated with worse outcomes in clinical prothrombotic situations. The procoagulant properties of EMP can be attributed to the expression of phospholipids, tissue factor and von-Willebrand factor on their surface. We therefore investigated whether addition of in-vitro generated EMP modifies hemostasis in plasma from patients with severe von-Willebrand disease (VWD). A large EMP pool was obtained from stimulated endothelial cell lines and EMP concentration was quantified by flow cytometry. The influence of EMP on primary and secondary hemostasis in VWD plasma was assessed using ristocetin-induced platelet aggregation (RIPA) and thrombin generation in a calibrated automated thrombogram (CAT), respectively. After addition of EMP, there was a significant increase in the maximal aggregation level in RIPA as well as a significant shortening of lag time and time-to-peak in CAT in comparison to control buffer. In summary, in vitro-generated EMP have the potential to improve hemostasis in severe VWD plasma and these results warrant further clinical reseach regarding their contribution to the clinical bleeding phenotype as well as their potential to improve replacement therapy.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. Electronic address: trummer.arne@mh-hannover.de.
authors.forename: Arne
authors.initials: A
authors.lastname: Trummer
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Werwitzke
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wermes
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Birschmann
authors.affiliation: Asklepios Clinic Altona, Medilys Central Laboratory Coagulation, Hamburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tiede
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D012310:Ristocetin / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood* / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D014841:von Willebrand Factor; D012310:Ristocetin; D013917:Thrombin
keywords: Microparticles; Ristocetin-induced platelet aggregation; Thrombin generation; Von-Willebrand disease