title: Surveillance of megakaryocytic function by measurement of CD61-exposing microparticles in allogeneic hematopoietic stem cell recipients.
abstract: Increasing evidence suggests that circulating microparticles (MP) exposing CD61 originate predominantly from megakaryocytes. Dramatic changes in megakaryocytic homeostasis are regularly observed following allogeneic hematopoietic stem cell transplantation (HSCT) and associated with transplantation-associated complications. We studied MP plasma levels prospectively in healthy subjects (n = 10) and allogeneic HSCT recipients (n = 19) twice weekly from the start of conditioning therapy up to day 30. A total of 224 measurement points were evaluated. MP were isolated, double-stained with annexin V and anti-CD61, and analyzed by flow cytometry. In uncomplicated HSCT, we found a correlation between platelet and CD61-exposing MP count, which resulted in a constant ratio of MP per platelet. The ratio was increased in patients with active hematological malignancies before transplantation and normalized during conditioning therapy. After take, the MP ratio increased, whereas infections and microangiopathic hemolytic anemia did not affect the ratio. In patients with GvHD, a decreased MP ratio was observed depending on the grade of GvHD, possibly indicating megakaryocytic damage. The MP ratio was able to discriminate between toxic, septic, and GvHD-induced hyperbilirubinemia. We first describe CD61+ MP levels during allogeneic HSCT and postulate that the MP ratio might be a useful biomarker for the surveillance of megakaryocytes during HSCT.
authors.affiliation: Medizinische Klinik III - Großhadern, Klinikum der Ludwig Maximilians-Universität München, München, Germany. andreas.rank@med.uni-muenchen.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Rank
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
authors.forename: Ruth
authors.initials: R
authors.lastname: Delker
authors.forename: Verena
authors.initials: V
authors.lastname: Pihusch
authors.forename: Ralf
authors.initials: R
authors.lastname: Wilkowski
authors.forename: Bettina
authors.initials: B
authors.lastname: Toth
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Rudolf
authors.initials: R
authors.lastname: Pihusch
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult