Patalakh I, Wandersee A, Schlüter J, Erdmann M, Hackstein H, Cunningham S (2024)
Publication Type: Journal article, Original article
Publication year: 2024
DOI: 10.1159/000535926
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.
APA:
Patalakh, I., Wandersee, A., Schlüter, J., Erdmann, M., Hackstein, H., & Cunningham, S. (2024). Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma. Transfusion Medicine and Hemotherapy. https://doi.org/10.1159/000535926
MLA:
Patalakh, Iryna, et al. "Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma." Transfusion Medicine and Hemotherapy (2024).
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