title: Defective platelet beta-N-acetyl hexosaminidase content and release in chronic myeloproliferative disorders.
abstract: OBJECTIVE
  Abnormalities of platelet function or structure are a hallmark of chronic myeloproliferative disorders (MPD). In vivo platelet activation with the release of alpha- and delta-granules in the circulation is one of the most frequently described alterations in MPD. Platelets contain and release upon activation also lysosomes, and in particular beta-N-acetylhexosaminidase (Hex). We have assessed whether the content and in vivo release of Hex of platelets from MPD patients is altered.
  
  
  METHODS
  Twenty-three MPD patients were compared with 19 age- and sex-matched healthy controls. The activity of platelet beta-N-acetylhexosaminidase was measured in plasma, serum and in the capillary blood emerging from the skin wound inflicted for the measurement of the bleeding time. Lysosome integral membrane protein (LIMP or CD63), lysosome-associated membrane protein (LAMP-2 or CD107b) and P-selectin were evaluated by flow cytometry. Platelet aggregation in vitro and the release of beta-N-acetylhexosaminidase, ATP and beta-thromboglobulin were performed to study platelet reactivity.
  
  
  RESULTS
  Hex levels in plasma were significantly higher in MPD than in controls while the release of Hex in the bleeding time blood, i.e. at a localized site of in vivo platelet plug formation, was lower in MPD and the platelet content of Hex was reduced. These changes were accompanied by in vivo platelet activation. Finally, the isoenzymatic pattern of Hex was altered in platelets of MPD patients, with a reduced amount of the Hex A isoform as compared with controls.b
  
  
  CONCLUSIONS
  MPD patients present an altered platelet Hex content and release; prospective studies to assess whether altered platelet Hex is related to thrombotic/hemorrhagic complications and/or tissue fibrosis in MPD are warranted.
authors.affiliation: Department of Biochemical Sciences and Molecular Biotechnologies, University of Perugia, Perugia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciferri
authors.forename: Simona
authors.initials: S
authors.lastname: Mencarelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mezzasoma
authors.forename: Stefania
authors.initials: S
authors.lastname: Momi
authors.forename: Aldo
authors.initials: A
authors.lastname: Orlacchio
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000201:enzymology* / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D054818:Hexosaminidase A; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000201:enzymology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010976:Platelet Count; D010979:Platelet Function Tests; D012016:Reference Values; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases