ArticleBlood advances2017
Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib.
Article in Blood advances, 2017. 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 68 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Cardiac safety profiles of first-generation vs second-generation BTK inhibitors: a meta-analysis.The oncologist · 2026Pooled it
- Trial
- Phase II study of acalabrutinib in ibrutinib-intolerant patients with relapsed/refractory chronic lymphocytic leukemia.Haematologica · 2021Trial
- Itraconazole Increases Ibrutinib Exposure 10-Fold and Reduces Interindividual Variation-A Potentially Beneficial Drug-Drug Interaction.Clinical and translational science · 2020Trial
- A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia.Blood · 2018Trial
- 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
- Cardiovascular Toxicity of BTKi in Chronic B-Cell Malignancies.Reviews in cardiovascular medicine · 2026Review
- Stent thrombosis associated with non-response to clopidogrel despite co-administration of aspirin and ibrutinib.European heart journal. Case reports · 2026Article
- Can drug-induced platelet dysfunction be reversed?Research and practice in thrombosis and haemostasis · 2026Review
- Delayed Cutaneous Ecchymosis with Bruton's Tyrosine Kinase Inhibitors and Breast Radiation: A Case Report.Advances in radiation oncology · 2025Article
- BTK inhibitors potently impair platelet aggregation as a class effect independent of BTK specificity or dose in CLL and MCL.Journal of clinical and experimental hematopathology : JCEH · 2025Article
- Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation.Thrombosis and haemostasis · 2025Article
- Bruton's Tyrosine Kinase: A Potential Novel Target for Neurological Disorders.Physiological research · 2025Review
- Btk inhibition: the importance of being selective.Blood advances · 2024Article
- Article
- Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia.Current hematologic malignancy reports · 2024Review
- Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents.Cancers · 2024Review
- Optimal use of BTK inhibitors in Waldenström's macroglobulinemia: combination or single drug approach?Therapeutic advances in hematology · 2024Review
- QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Preclinical evidence for the effective use of TL-895, a highly selective and potent second-generation BTK inhibitor, for the treatment of B-cell malignancies.Scientific reports · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide, and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, whereas size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited Src family kinases, which have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of von Willebrand factor (VWF) and factor VIII (FVIII) ex vivo by addition of intermediate purity FVIII (Haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma VWF and FVIII.
Identifiers
What OpenQuestion holds
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.