ArticleBlood2022
Deletion of platelet CLEC-2 decreases GPIbα-mediated integrin αIIbβ3 activation and decreases thrombosis in TTP.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05568147 (A Prospective Multicenter Clinical Study of Aspirin for Prophylaxis in Patients With Hereditary or Acquired Thrombotic Thrombocytopenic Purpura), which is not on this map. Cited by 14 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Prospective Multicenter Clinical Study of Aspirin for Prophylaxis in Patients With Hereditary or Acquired Thrombotic Thrombocytopenic Purpura
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Platelet CLEC-2 activation leads to GPIb⍺ shedding: Implications for doxorubicin chemotherapy and thrombosis.The Journal of biological chemistry · 2026Article
- Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation.The Journal of clinical investigation · 2025Article
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- New insights of glycoprotein Ib-IX-V complex organization and glycoprotein Ibα in platelet biogenesis.Current opinion in hematology · 2024Review
- Hereditary Thrombotic Thrombocytopenic Purpura.Genes · 2023Review
- Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as a therapeutic target in COVID-19.Blood advances · 2023Article
- Antibody-mediated depletion of human CLEC-2 in a novel humanized mouse model.Blood advances · 2023Article
- Identification of thrombotic biomarkers in orthopedic surgery patients by plasma proteomics.Journal of orthopaedic surgery and research · 2023Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- CLEC-2 Supports Platelet Aggregation in Mouse but not Human Blood at Arterial Shear.Thrombosis and haemostasis · 2022Article
- Hereditary thrombotic thrombocytopenic purpura: The risk for death at birth.Research and practice in thrombosis and haemostasis · 2022Article
- Aspirin prophylaxis for hereditary and acquired thrombotic thrombocytopenic purpura?American journal of hematology · 2022Article
- Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Microvascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP) is initiated by GPIbα-mediated platelet binding to von Willebrand factor (VWF). Binding of VWF to GPIbα causes activation of the platelet surface integrin αIIbβ3. However, the mechanism of GPIbα-initiated activation of αIIbβ3 and its clinical importance for microvascular thrombosis remain elusive. Deletion of platelet C-type lectin-like receptor 2 (CLEC-2) did not prevent VWF binding to platelets but specifically inhibited platelet aggregation induced by VWF binding in mice. Deletion of platelet CLEC-2 also inhibited αIIbβ3 activation induced by the binding of VWF to GPIbα. Using a mouse model of TTP, which was created by infusion of anti-mouse ADAMTS13 monoclonal antibodies followed by infusion of VWF, we found that deletion of platelet CLEC-2 decreased pulmonary arterial thrombosis and the severity of thrombocytopenia. Importantly, prophylactic oral administration of aspirin, an inhibitor of platelet activation, and therapeutic treatment of the TTP mice with eptifibatide, an integrin αIIbβ3 antagonist, reduced pulmonary arterial thrombosis in the TTP mouse model. Our observations demonstrate that GPIbα-mediated activation of integrin αIIbβ3 plays an important role in the formation of thrombosis in TTP. These observations suggest that prevention of platelet activation with aspirin may reduce the risk for thrombosis in patients with TTP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.