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  1. Article ; Online: Megakaryocyte buds are distinct from microvesicles and likely to represent platelet precursors.

    Ellis, Marc L / Alwis, Imala / Smythe, Rhyll / Yuan, Yuping / Jackson, Shaun P

    Blood advances

    2022  Volume 7, Issue 6, Page(s) 982–986

    MeSH term(s) Megakaryocytes ; Blood Platelets ; Platelet Count
    Language English
    Publishing date 2022-11-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2022008850
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7153: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: GPIbα-filamin A interaction regulates megakaryocyte localization and budding during platelet biogenesis.

    Ellis, Marc L / Terreaux, Antoine / Alwis, Imala / Smythe, Rhyll / Perdomo, Jose / Eckly, Anita / Cranmer, Susan L / Passam, Freda H / Maclean, Jessica / Schoenwaelder, Simone M / Ruggeri, Zaverio M / Lanza, Francois / Taoudi, Samir / Yuan, Yuping / Jackson, Shaun P

    Blood

    2023  Volume 143, Issue 4, Page(s) 342–356

    Abstract: Abstract: Glycoprotein Ibα (GPIbα) is expressed on the surface of platelets and megakaryocytes (MKs) and anchored to the membrane skeleton by filamin A (flnA). Although GPIb and flnA have fundamental roles in platelet biogenesis, the nature of this ... ...

    Abstract Abstract: Glycoprotein Ibα (GPIbα) is expressed on the surface of platelets and megakaryocytes (MKs) and anchored to the membrane skeleton by filamin A (flnA). Although GPIb and flnA have fundamental roles in platelet biogenesis, the nature of this interaction in megakaryocyte biology remains ill-defined. We generated a mouse model expressing either human wild-type (WT) GPIbα (hGPIbαWT) or a flnA-binding mutant (hGPIbαFW) and lacking endogenous mouse GPIbα. Mice expressing the mutant GPIbα transgene exhibited macrothrombocytopenia with preserved GPIb surface expression. Platelet clearance was normal and differentiation of MKs to proplatelets was unimpaired in hGPIbαFW mice. The most striking abnormalities in hGPIbαFW MKs were the defective formation of the demarcation membrane system (DMS) and the redistribution of flnA from the cytoplasm to the peripheral margin of MKs. These abnormalities led to disorganized internal MK membranes and the generation of enlarged megakaryocyte membrane buds. The defective flnA-GPIbα interaction also resulted in misdirected release of buds away from the vasculature into bone marrow interstitium. Restoring the linkage between flnA and GPIbα corrected the flnA redistribution within MKs and DMS ultrastructural defects as well as restored normal bud size and release into sinusoids. These studies define a new mechanism of macrothrombocytopenia resulting from dysregulated MK budding. The link between flnA and GPIbα is not essential for the MK budding process, however, it plays a major role in regulating the structure of the DMS, bud morphogenesis, and the localized release of buds into the circulation.
    MeSH term(s) Animals ; Humans ; Mice ; Blood Platelets/metabolism ; Cytoplasm/metabolism ; Filamins/genetics ; Filamins/metabolism ; Megakaryocytes/metabolism ; Morphogenesis ; Platelet Glycoprotein GPIb-IX Complex/genetics ; Platelet Glycoprotein GPIb-IX Complex/metabolism ; Thrombocytopenia/genetics ; Thrombocytopenia/metabolism
    Chemical Substances Filamins ; Platelet Glycoprotein GPIb-IX Complex
    Language English
    Publishing date 2023-11-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023021292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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  3. Article ; Online: Catheter-related thrombosis incidence and risk factors in adult cancer patients with central venous access devices.

    Ellis, Marc L / Okano, Satomi / McCann, Andrew / McDowall, Angela / Van Kuilenburg, Rosita / McCarthy, Alexandra L / Joubert, Warren / Harper, John / Jones, Mark / Mollee, Peter

    Internal medicine journal

    2020  Volume 50, Issue 12, Page(s) 1475–1482

    Abstract: Background: Central venous access devices (CVAD) are commonly employed in the management of cancer patients. While having several benefits they are associated with significant risks.: Aim: To review the incidence and risk factors for catheter-related ...

    Abstract Background: Central venous access devices (CVAD) are commonly employed in the management of cancer patients. While having several benefits they are associated with significant risks.
    Aim: To review the incidence and risk factors for catheter-related thrombosis (CRT) in cancer patients with a CVAD.
    Methods: We performed a prospective observational cohort study of adult patients with cancer requiring a CVAD between 1 January 2004 and 29 June 2016. The rate of, and risk factors for the development of, symptomatic CRT were evaluated.
    Results: A total of 4920 central lines was inserted into 3130 patients. The incidence of CRT was 3.6%. CRT developed a median of 12 days following line insertion. Peripherally inserted central catheters (PICC) were associated with the highest rates of CRT (hazards ratio (HR) 22.2, 95% confidence interval (CI) 2.9-170.6). Older age groups developed CRT at lower rates (HR 0.57; 95% CI 0.39-0.84 for age 50-61 years, and HR 0.63; 95% CI 0.45-0.89 for age >61 years) compared to age <50 years. Increased CRT was seen in patients with prior CRT (HR 1.81; 95% CI 1.19-2.77). There was a trend to more CRT events with a Khorana tumour score of 1 compared to those with a score of 0 (HR 1.37, 95% CI 1.00-1.88). Hodgkin lymphoma, germ cell and oesophagus cancers had the highest CRT rates. Side of insertion was not associated with thrombosis risk (HR 0.77; 95% CI 0.57-1.05; P = 0.10).
    Conclusions: Age <50 years, PICC lines and prior CRT were associated with highest CRT rate. Cancer subtype and insertion side were not predictive of thrombosis.
    MeSH term(s) Adult ; Aged ; Catheterization, Central Venous/adverse effects ; Humans ; Incidence ; Middle Aged ; Neoplasms/epidemiology ; Neoplasms/therapy ; Prospective Studies ; Risk Factors ; Thrombosis/epidemiology ; Thrombosis/etiology
    Language English
    Publishing date 2020-01-28
    Publishing country Australia
    Document type Journal Article ; Observational Study
    ZDB-ID 2045436-3
    ISSN 1445-5994 ; 1444-0903
    ISSN (online) 1445-5994
    ISSN 1444-0903
    DOI 10.1111/imj.14780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 792: Show issues Location:
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    Zs.MO 424: Show issues

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