ArticleBlood advances2019
Oral Bruton tyrosine kinase inhibitors block activation of the platelet Fc receptor CD32a (FcγRIIA): a new option in HIT?
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Monoclonal Gammopathy of Thrombotic Significance.American journal of hematology · 2026Review
- Monovalent Anti-FcγRIIA Antibody Blocks Immune-Mediated Thrombocytopenia and Thrombosis With Minimal Adverse Side Effects in Mice.Arteriosclerosis, thrombosis, and vascular biology · 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
- Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.Clinical and experimental medicine · 2026Review
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Simulation of perioperative Ibrutinib withdrawal using a population pharmacokinetic model and sparse clinical concentration data.Cancer chemotherapy and pharmacology · 2025Article
- Comprehensive Characterization of Bruton's Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures.ACS pharmacology & translational science · 2025Review
- Anti-Platelet factor 4 immunothrombosis-not just heparin and vaccine triggers.Research and practice in thrombosis and haemostasis · 2025Review
- COVID-19 vaccine-induced immune thrombotic thrombocytopenia: pathophysiology and diagnosis.Annals of hematology · 2025Review
- Advances in our understanding of anti-PF4 related immunothrombosis.Frontiers in immunology · 2025Review
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents.Cancers · 2024Review
- Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis.Combinatorial chemistry & high throughput screening · 2024Article
- Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies.Experimental hematology & oncology · 2023Review
- Current concepts and novel targets for antiplatelet therapy.Nature reviews. Cardiology · 2023Review
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- Platelet-neutrophil interaction in COVID-19 and vaccine-induced thrombotic thrombocytopenia.Frontiers in immunology · 2023Review
- Mechanism Research of Platelet Core Marker Prediction and Molecular Recognition in Cardiovascular Events.Combinatorial chemistry & high throughput screening · 2023Article
- Chemokines, molecular drivers of thromboinflammation and immunothrombosis.Frontiers in immunology · 2023Review
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the platelet Fc-receptor CD32a (FcγRIIA) is an early and crucial step in the pathogenesis of heparin-induced thrombocytopenia type II (HIT) that has not been therapeutically targeted. Downstream FcγRIIA Bruton tyrosine kinase (BTK) is activated; however, its role in Fc receptor-induced platelet activation is unknown. We explored the potential to prevent FcγRIIA-induced platelet activation by BTK inhibitors (BTKi's) approved (ibrutinib, acalabrutinib) or in clinical trials (zanubrutinib [BGB-3111] and tirabrutinib [ONO/GS-4059]) for B-cell malignancies, or in trials for autoimmune diseases (evobrutinib, fenebrutinib [GDC-0853]). We found that all BTKi's blocked platelet activation in blood after FcγRIIA stimulation by antibody-mediated cross-linking (inducing platelet aggregation and secretion) or anti-CD9 antibody (inducing platelet aggregation only). The concentrations that inhibit 50% (IC50) of FcγRIIA cross-linking-induced platelet aggregation were for the irreversible BTKi's ibrutinib 0.08 µM, zanubrutinib 0.11 µM, acalabrutinib 0.38 µM, tirabrutinib 0.42 µM, evobrutinib 1.13 µM, and for the reversible BTKi fenebrutinib 0.011 µM. IC50 values for ibrutinib and acalabrutinib were four- to fivefold lower than the drug plasma concentrations in patients treated for B-cell malignancies. The BTKi's also suppressed adenosine triphosphate secretion, P-selectin expression, and platelet-neutrophil complex formation after FcγRIIA cross-linking. Moreover, platelet aggregation in donor blood stimulated by sera from HIT patients was blocked by BTKi's. A single oral intake of ibrutinib (280 mg) was sufficient for a rapid and sustained suppression of platelet FcγRIIA activation. Platelet aggregation by adenosine 5'-diphosphate, arachidonic acid, or thrombin receptor-activating peptide was not inhibited. Thus, irreversible and reversible BTKi's potently inhibit platelet activation by FcγRIIA in blood. This new rationale deserves testing in patients with HIT.
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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.