Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab
Related Experiment Video
Updated: Feb 13, 2026
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Maudy Walraven1,2, Marjolein Y V Homs3, Astrid A M van der Veldt1,3
1Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan, 1117, 1081 HV, Amsterdam, The Netherlands.
Introduction:
At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings.
Materials And Methods:
In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet-EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC-MS/MS and ELISA.
Results:
In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 μM sunitinib: 71.3%, p < 0.001; 25 μM sorafenib: 55.8%, p = 0.042). Sorafenib and sunitinib significantly inhibited P-selectin expression on platelets. Exposure to both TKIs resulted in a reduced tyrosine phosphorylation of c-Src. Ex vivo, within 24 h sunitinib impaired platelet aggregation (83.0%, p = 0.001, N = 8). Plasma concentrations of sunitinib, VEGF, and platelet/EC activation markers were not correlated with disturbed aggregation. In contrast, bevacizumab only significantly impaired platelet aggregation in vitro at high concentrations, but not ex vivo.
Conclusion:
Sunitinib significantly inhibits platelet aggregation in patients already after 24 h of first administration, whereas bevacizumab had no effect on aggregation. These findings may explain the clinically observed bleedings during treatment with antiangiogenic TKIs.
Insights
Sunitinib, a tyrosine kinase inhibitor (TKI), significantly impairs platelet aggregation within 24 hours, potentially explaining bleeding risks. Bevacizumab did not affect platelet aggregation in patients.
Area of Science:
- Oncology
- Pharmacology
- Hematology
Background:
- Antiangiogenic agents, initially expected to have minimal toxicity, have revealed serious side effects.
- The mechanisms underlying toxicities, particularly bleeding, associated with these agents are largely unknown.
- Platelet dysfunction is a potential contributor to treatment-related bleeding events.
Purpose of the Study:
- To investigate the impact of sunitinib, sorafenib, and bevacizumab on platelet function.
- To determine if impaired platelet function by these antiangiogenic drugs explains observed bleeding complications.
Main Methods:
- In vitro studies assessed platelet aggregation, P-selectin expression, and c-Src phosphorylation using optical aggregation, flow cytometry, and western blotting.
- Ex vivo analysis evaluated platelet aggregation in patients treated with sunitinib or bevacizumab.
- Concentrations of sunitinib, VEGF, and activation markers were quantified.
Main Results:
- Sunitinib and sorafenib significantly inhibited platelet aggregation and P-selectin expression in vitro.
- Both TKIs reduced tyrosine phosphorylation of c-Src.
- Ex vivo, sunitinib markedly impaired platelet aggregation within 24 hours of administration.
- Bevacizumab showed minimal impact on platelet aggregation in vitro and no significant effect ex vivo.
Conclusions:
- Sunitinib significantly inhibits platelet aggregation in patients shortly after administration.
- Bevacizumab does not appear to impair platelet aggregation in patients.
- These findings provide a mechanistic explanation for bleeding complications observed with antiangiogenic TKIs like sunitinib.
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