ArticleHaematologica2021
Low-dose Btk inhibitors selectively block platelet activation by CLEC-2.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Activation of Platelet Caspase-1 and P-Selectin Over-Expression in Sickle Cell Disease Patients: An Involvement of NLRP3 Inflammasome?Journal of cellular and molecular medicine · 2026Article
- Comparison of variably specific Bruton tyrosine kinase inhibitors on platelet aggregation mediated by Fcγ receptor (FcγR) IIa, glycoprotein VI, and platelet endothelial aggregation receptor (PEAR) 1: implications for Bruton tyrosine kinase inhibitors as antithrombotic therapy.Research and practice in thrombosis and haemostasis · 2026Article
- Inflammatory cytokines, inflammasomes, and neutrophil extracellular traps in primary immune thrombocytopenia pathogenesis.Blood vessels, thrombosis & hemostasis · 2026Review
- Platelet activation, aspirin, and cancer: From basic science to clinical trials.Pharmacological reviews · 2026Review
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice.Blood advances · 2024Article
- C-type lectin-like receptor 2: roles and drug target.Thrombosis journal · 2024Review
- The role of platelets in sepsis: A review.Biomolecules & biomedicine · 2024Review
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- Chemical degradation of BTK/TEC as a novel approach to inhibit platelet function.Blood advances · 2023Article
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
- Bruton's tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome.Frontiers in immunology · 2023Article
- CLEC-2 Supports Platelet Aggregation in Mouse but not Human Blood at Arterial Shear.Thrombosis and haemostasis · 2022Article
- The Btk inhibitor AB-95-LH34 potently inhibits atherosclerotic plaque-induced thrombus formation and platelet procoagulant activity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Novel Antithrombotic Agents in Ischemic Cardiovascular Disease: Progress in the Search for the Optimal Treatment.Journal of cardiovascular development and disease · 2022Review
- Anti-GPVI nanobody blocks collagen- and atherosclerotic plaque-induced GPVI clustering, signaling, and thrombus formation.Journal of thrombosis and haemostasis : JTH · 2022Article
- Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib.Research and practice in thrombosis and haemostasis · 2022Article
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
- Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs.International journal of molecular sciences · 2022Article
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20 authors at 6 institutions in 3 countries.
Funding
Abstract
Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease.
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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.