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  1. Article ; Online: Preeclampsia: Platelet procoagulant membrane dynamics and critical biomarkers.

    Agbani, Ejaife O / Skeith, Leslie / Lee, Adrienne

    Research and practice in thrombosis and haemostasis

    2023  Volume 7, Issue 2, Page(s) 100075

    Abstract: A state-of-the-art lecture titled "Preeclampsia and Platelet Procoagulant Membrane Dynamics" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. Platelet activation is involved in the pathophysiology of ... ...

    Abstract A state-of-the-art lecture titled "Preeclampsia and Platelet Procoagulant Membrane Dynamics" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. Platelet activation is involved in the pathophysiology of preeclampsia and contributes to the prothrombotic state of the disorder. Still, it remains unclear what mechanisms initiate and sustain platelet activation in preeclampsia and how platelets drive the thrombo-hemorrhagic abnormalities in preeclampsia. Here, we highlight our findings that platelets in preeclampsia are preactivated possibly by plasma procoagulant agonist(s) and overexpress facilitative glucose transporter-3 (GLUT3) in addition to GLUT1. Preeclampsia platelets are also partially degranulated, procoagulant, and proaggregatory and can circulate as microaggregates/microthrombi. However, in response to exposed subendothelial collagen, such as in injured vessels during cesarean sections, preeclampsia platelets are unable to mount a full procoagulant response, contributing to blood loss perioperatively. The overexpression of GLUT3 or GLUT1 may be monitored alone or in combination (GLUT1/GLUT3 ratio) as a biomarker for preeclampsia onset, phenotype, and progression. Studies to further understand the mediators of the platelet activation and procoagulant membrane dynamics in preeclampsia can reveal novel drug targets and suitable alternatives to aspirin for the management of prothrombotic tendencies in preeclampsia. Finally, we summarize relevant new data on this topic presented during the 2022 ISTH Congress.
    Language English
    Publishing date 2023-02-08
    Publishing country United States
    Document type Journal Article
    ISSN 2475-0379
    ISSN (online) 2475-0379
    DOI 10.1016/j.rpth.2023.100075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Platelet procoagulant membrane dynamics: a key distinction between thrombosis and hemostasis?

    Agbani, Ejaife O / Hers, Ingeborg / Poole, Alastair W

    Blood advances

    2022  Volume 7, Issue 8, Page(s) 1615–1619

    MeSH term(s) Humans ; Blood Platelets ; Hemostasis ; Thrombosis/diagnosis ; Thrombosis/etiology
    Language English
    Publishing date 2022-12-29
    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.2022008122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Aquaporins in platelet function.

    Agbani, Ejaife O / Poole, Alastair W

    Platelets

    2021  Volume 32, Issue 7, Page(s) 895–901

    Abstract: Structurally, aquaporins (AQPs) are small channel proteins with monomers of ~ 30 kDa that are assembled as tetramers to form pores on cell membranes. Aquaporins mediate the conduction of water but at times also small solutes including glycerol across ... ...

    Abstract Structurally, aquaporins (AQPs) are small channel proteins with monomers of ~ 30 kDa that are assembled as tetramers to form pores on cell membranes. Aquaporins mediate the conduction of water but at times also small solutes including glycerol across cell membranes and along osmotic gradients. Thirteen isoforms of AQPs have been reported in mammalian cells, and several of these are likely expressed in platelets. Osmotic swelling mediated by AQP1 sustains the calcium entry required for platelet phosphatidylserine exposure and microvesiculation, through calcium permeable stretch-activated or mechanosensitive cation channels. Notably, deletion of AQP1 diminishes platelet procoagulant membrane dynamics
    MeSH term(s) Aquaporins/metabolism ; Blood Platelets/metabolism ; Humans ; Models, Molecular ; Platelet Function Tests/methods
    Chemical Substances Aquaporins
    Language English
    Publishing date 2021-04-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2021.1904133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Activated Platelets Harbor SARS-CoV-2 during Severe COVID-19.

    Agbani, Ejaife O / Schneider, Prism / McDonald, Braedon / Skeith, Leslie / Poon, Man-Chiu / Lee, Adrienne

    Thrombosis and haemostasis

    2021  Volume 122, Issue 2, Page(s) 308–309

    Language English
    Publishing date 2021-12-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/a-1683-8455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Letter by Agbani et al Regarding Article, "Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface".

    Agbani, Ejaife O / Hers, Ingeborg / Poole, Alastair W

    Arteriosclerosis, thrombosis, and vascular biology

    2019  Volume 39, Issue 12, Page(s) e287–e289

    MeSH term(s) Blood Platelets ; Humans ; Platelet Activation ; Thrombosis
    Language English
    Publishing date 2019-11-26
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.119.313468
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Membrane procoagulation and N‑terminomics/TAILS profiling in Montreal platelet syndrome kindred with VWF p.V1316M mutation.

    Agbani, Ejaife O / Young, Daniel / Chen, Si An / Smith, Sophie / Lee, Adrienne / Poole, Alastair W / Dufour, Antoine / Poon, Man-Chiu

    Communications medicine

    2023  Volume 3, Issue 1, Page(s) 125

    Abstract: Background: The Montreal platelet syndrome kindred (MPS) with VWF p.V1316M mutation (2B-VWDMPS) is an extremely rare disorder. It has been associated with macrothrombocytopenia, spontaneous platelet clumping, mucocutaneous, and other bleeding, which can ...

    Abstract Background: The Montreal platelet syndrome kindred (MPS) with VWF p.V1316M mutation (2B-VWDMPS) is an extremely rare disorder. It has been associated with macrothrombocytopenia, spontaneous platelet clumping, mucocutaneous, and other bleeding, which can be largely prevented by von Willebrand factor (VWF) concentrate infusion. However, supplemental platelet transfusion has been required on occasion, particularly for severe gastrointestinal bleeds. This raised the question of whether a previously uncharacterized platelet dysfunction contributes to bleeding diathesis in 2B-VWDMPS patients. We have previously shown that membrane ballooning, a principal part of the platelet procoagulant membrane dynamics (PMD) after collagen stimulation, is driven by the influx of Na
    Methods: We study two members (mother and daughter) of the MPS kindred with severe bleeding phenotype and address this question by coupling quantitative platelet shotgun proteomics and validating biochemical assays, with the systematic analysis of platelet procoagulant membrane dynamics (PMD). Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compare changes in proteolysis between healthy and 2B-VWDMPS platelets.
    Results: Here, we report in 2B-VWDMPS platelets, the loss of the transmembrane chloride channel-1 (CLIC1), and reduced chloride ion influx after collagen stimulation. This was associated with diminished membrane ballooning, phosphatidylserine externalization, and membrane thrombin formation, as well as a distinct phenotypic composition of platelets over fibrillar collagen. We also identify processing differences of VWF, fibronectin (FN1), and Crk-like protein (CRKL). 2B-VWDMPS platelets are shown to be basally activated, partially degranulated, and have marked loss of regulatory, cytoskeletal, and contractile proteins.
    Conclusions: This may account for structural disorganization, giant platelet formation, and a weakened hemostatic response.
    Language English
    Publishing date 2023-09-21
    Publishing country England
    Document type Journal Article
    ISSN 2730-664X
    ISSN (online) 2730-664X
    DOI 10.1038/s43856-023-00354-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Platelets and neutrophils co-drive procoagulant potential in secondary antiphospholipid syndrome during pregnancy.

    Agbani, Ejaife O / Mahe, Etienne / Chaturvedi, Shruti / Yamaura, Lisa / Schneider, Prism / Barber, Megan R W / Choi, May / Lee, Adrienne / Skeith, Leslie

    Thrombosis research

    2022  Volume 220, Page(s) 141–144

    MeSH term(s) Humans ; Female ; Pregnancy ; Blood Platelets ; Neutrophils ; Antiphospholipid Syndrome/complications
    Language English
    Publishing date 2022-11-03
    Publishing country United States
    Document type Letter
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2022.10.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Low α-Thrombin/GPIbα Interaction Is a Potential Contributor to Platelet Hyper-reactivity in COVID-19 Patients.

    Zaid, Younes / Khalki, Loubna / Jalali, Farid / Tijani, Youssef / Zaid, Nabil / Naya, Abdallah / Oudghiri, Mounia / Akarid, Khadija / Agbani, Ejaife O / Guessous, Fadila

    Thrombosis and haemostasis

    2023  Volume 123, Issue 8, Page(s) 804–807

    MeSH term(s) Humans ; Thrombin/metabolism ; COVID-19 ; Blood Platelets/metabolism ; Platelet Aggregation ; Platelet Glycoprotein GPIb-IX Complex/metabolism ; Protein Binding
    Chemical Substances Thrombin (EC 3.4.21.5) ; Platelet Glycoprotein GPIb-IX Complex
    Language English
    Publishing date 2023-04-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/a-2072-0366
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Membrane procoagulation and N‑terminomics/TAILS profiling in Montreal platelet syndrome kindred with VWF p.V1316M mutation

    Ejaife O. Agbani / Daniel Young / Si An Chen / Sophie Smith / Adrienne Lee / Alastair W. Poole / Antoine Dufour / Man-Chiu Poon

    Communications Medicine, Vol 3, Iss 1, Pp 1-

    2023  Volume 9

    Abstract: Abstract Background The Montreal platelet syndrome kindred (MPS) with VWF p.V1316M mutation (2B-VWDMPS) is an extremely rare disorder. It has been associated with macrothrombocytopenia, spontaneous platelet clumping, mucocutaneous, and other bleeding, ... ...

    Abstract Abstract Background The Montreal platelet syndrome kindred (MPS) with VWF p.V1316M mutation (2B-VWDMPS) is an extremely rare disorder. It has been associated with macrothrombocytopenia, spontaneous platelet clumping, mucocutaneous, and other bleeding, which can be largely prevented by von Willebrand factor (VWF) concentrate infusion. However, supplemental platelet transfusion has been required on occasion, particularly for severe gastrointestinal bleeds. This raised the question of whether a previously uncharacterized platelet dysfunction contributes to bleeding diathesis in 2B-VWDMPS patients. We have previously shown that membrane ballooning, a principal part of the platelet procoagulant membrane dynamics (PMD) after collagen stimulation, is driven by the influx of Na+ and Cl-, followed by the entry of water. Methods We study two members (mother and daughter) of the MPS kindred with severe bleeding phenotype and address this question by coupling quantitative platelet shotgun proteomics and validating biochemical assays, with the systematic analysis of platelet procoagulant membrane dynamics (PMD). Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compare changes in proteolysis between healthy and 2B-VWDMPS platelets. Results Here, we report in 2B-VWDMPS platelets, the loss of the transmembrane chloride channel-1 (CLIC1), and reduced chloride ion influx after collagen stimulation. This was associated with diminished membrane ballooning, phosphatidylserine externalization, and membrane thrombin formation, as well as a distinct phenotypic composition of platelets over fibrillar collagen. We also identify processing differences of VWF, fibronectin (FN1), and Crk-like protein (CRKL). 2B-VWDMPS platelets are shown to be basally activated, partially degranulated, and have marked loss of regulatory, cytoskeletal, and contractile proteins. Conclusions This may account for structural disorganization, giant platelet formation, and a weakened hemostatic response.
    Keywords Medicine ; R
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis.

    Agbani, Ejaife O / Poole, Alastair W

    Blood

    2017  Volume 130, Issue 20, Page(s) 2171–2179

    Abstract: Current understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range ... ...

    Abstract Current understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range of descriptive titles and attributes. We identify striking overlaps in the reported characteristics of these platelets, which imply a single subpopulation of versatile platelets and thus suggest that their commonality requires unification of their description. We therefore propose the term procoagulant platelet as the unifying terminology. We discuss the agonist requirements and molecular drivers for the dramatic morphological transformation platelets undergo when becoming procoagulant. Finally, we provide perspectives on the biomarker potential of procoagulant platelets for thrombotic events as well as on the possible clinical benefits of inhibitors of carbonic anhydrase enzymes and the water channel Aquaporin-1 for targeting this subpopulation of platelets as antiprocoagulant antithrombotics.
    MeSH term(s) Animals ; Blood Coagulation/drug effects ; Blood Coagulation/physiology ; Blood Platelets/drug effects ; Blood Platelets/physiology ; Humans ; Molecular Targeted Therapy/methods ; Thrombosis/blood ; Thrombosis/drug therapy
    Language English
    Publishing date 2017-09-27
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2017-05-787259
    Database MEDical Literature Analysis and Retrieval System OnLINE

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