Defective platelet β-N-acetyl hexosaminidase content and release in chronic myeloproliferative disorders

• Published in: Platelets (Edinburgh) 2006-02, Vol.17 (1), p.20-29
• Main Authors: Emiliani, Carla, Ciferri, Silvia, Mencarelli, Simona, Mezzasoma, Anna Maria, Momi, Stefania, Orlacchio, Aldo, Gresele, Paolo
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; beta-N-Acetylhexosaminidases - deficiency; beta-N-Acetylhexosaminidases - metabolism; Bleeding time; Blood Coagulation Tests; Blood Platelets - enzymology; Blood Platelets - physiology; Chronic Disease; Female; flow-cytometry; Hexosaminidase A; Humans; In Vitro Techniques; Isoenzymes - deficiency; Isoenzymes - metabolism; lysosomes; Lysosomes - metabolism; Male; Middle Aged; Myeloproliferative Disorders - diagnosis; Myeloproliferative Disorders - enzymology; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Platelet Count; Platelet Function Tests; platelet secretion; Reference Values; β-hexosaminidase
• ISSN: 0953-7104; 1369-1635
• DOI: 10.1080/09537100500235958

Background and objectives: Abnormalities of platelet function or structure are a hallmark of chronic myeloproliferative disorders (MPD). In vivo platelet activation with the release of α- and δ-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 β-N-acetylhexosaminidase (Hex). We have assessed whether the content and in vivo release of Hex of platelets from MPD patients is altered. Design and methods: Twenty-three MPD patients were compared with 19 age- and sex-matched healthy controls. The activity of platelet β-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 β-N-acetylhexosaminidase, ATP and β-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. Interpretations and 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.