Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation

Schlüter, Julian; Cunningham, Sarah; Zimmermann, Robert A.; Achenbach, Susanne; Kramer, Rafaela; Erdmann, Michael; Beckmann, M.; Heinzerling, Lucie; Hackstein, Holger

doi:10.1016/j.imbio.2022.152311

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…The platelet concept has shifted from unique hemostatic and pro-coagulant roles to a broader function including defense against pathogens, immune regulation, and finally, participation in malignant diseases. Platelets have been recognized as important participants in inflammation, innate immunity, growth and development, vascular integrity and angiogenesis, wound healing, and finally, cancer [1] . These anuclear blood cells function as reporters and transporters within the tumor microenvironment (TME) [2] .…”

Section: Introductionmentioning

confidence: 99%

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Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development

Trivanović,

Mojsilović,

Bogosavljević

et al. 2024

Translational Oncology

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Section: Introductionmentioning

confidence: 99%

“…In cancer patients, plasma thrombotic markers are dysregulated with activation of blood coagulation and fibrinolysis following the cancer development and progression. Moreover, TF within the stromal compartment of the TME pointed out the importance of the hemostasis and cancer interaction [ 1 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development

Trivanović,

Mojsilović,

Bogosavljević

et al. 2024

Translational Oncology

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Revelation of benzo(a)pyrene-induced latent toxicity mechanism to intestinal histomorphology and oxidative status for common carp (Cyprinus carpio) through transcriptional and single-cell sequencing

Hao,

Chen,

Fan

et al. 2024

Aquaculture

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Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma

Patalakh,

Wandersee,

Schlüter

et al. 2024

Transfus Med Hemother

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Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized classical treatment approaches of various cancer entities, but are also associated with a number of side effects. One of these may be life-threatening clotting disorders with the risk of thrombotic or hemorrhagic complications, the mechanisms of which are still poorly understood. In the present study, we analyzed the direct effects of pembrolizumab, nivolumab, and ipilimumab on platelet aggregation as well as plasma coagulation followed by fibrinolysis in an ex vivo model. Methods: Microplate spectrometry was used to analyze aggregation, coagulation, and fibrinolysis in platelet-free (PFP) and platelet-rich (PRP) healthy donor plasma samples treated with pembrolizumab, nivolumab, ipilimumab, and appropriate isotype controls. Aggregation was induced by TRAP-6. Clotting of PFP and PRP followed by lysis was initiated with a tissue factor in a mixture of phosphatidylserine:phosphatidylcholine and the addition of t-PA. Among other parameters, the area under the curve (AUC) was used to compare the effect of ICIs on aggregation, coagulation, and fibrinolysis. Results: Upon direct contact with platelets, pembrolizumab stimulated platelet aggregation in PRP, while nivolumab and ipilimumab promoted disaggregation with corresponding changes in the AUC. Pembrolizumab and nivolumab, both PD-1 receptor inhibitors, had no effect on the plasma coagulation cascade. Ipilimumab, a CTLA-4 receptor inhibitor, significantly increased the rate of PRP clotting. When clotting was followed by lysis, all ICIs were found to prolong the growth of the PRP-derived fibrin clot and delay its elimination. This was manifested by an increase in AUC relative to control PRP. Conclusion: This study characterizes the potential impact of pembrolizumab, nivolumab, and ipilimumab on hemostasis. Nivolumab and ipilimumab are able to reduce aggregation and increase the procoagulant properties of platelets, which can cause side effects associated with hemostatic imbalance leading to thrombosis or bleeding. The observed ICI-specific effects may contribute to our understanding of the mechanisms by which ICI affects platelets and suggest how, in a clinical setting, to reduce coagulation disorders during ICI treatment in the future.

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Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation

Cited by 3 publications

References 51 publications

Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development

Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development

Revelation of benzo(a)pyrene-induced latent toxicity mechanism to intestinal histomorphology and oxidative status for common carp (Cyprinus carpio) through transcriptional and single-cell sequencing

Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma

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