Abstract Number: PB1686
Meeting: ISTH 2020 Congress
Background: Sunitinib is a multi-target tyrosine kinase inhibitor (TKI) used for treatment of patients with solid tumors, and is associated with an increased bleeding risk. We previously showed that platelets sequester sunitinib, which affects activation responses. Cardiovascular disease is a common co-morbidity in cancer patients, resulting in additional anti-platelet treatment. The additive effect of anti-platelet drugs on top of sunitinib treatment is unclear.
Aims: Investigating consequences of the antiplatelet drug aspirin in combination with sunitinib treatment on platelet activation properties and secondary coagulation.
Methods: Whole blood or isolated platelets from healthy volunteers were incubated with sunitinib and/or aspirin or vehicle. In addition, blood was used from aspirin-treated healthy volunteers. Platelet activation by flow cytometry, changes in [Ca2+]i, light transmission aggregometry and whole blood perfusion over collagen alone or co-coated with tissue factor (TF) were measured.
Results: Sunitinib dose-dependently suppressed glycoprotein (GP)VI-induced platelet procoagulant activity and rises in [Ca2+]i in washed platelets. Reduced exposure of phosphatidylserine (PS) was also observed in thrombi after perfusion of sunitinib-treated whole blood over collagen at high shear rate; this was paralleled by decreased thrombus formation. In the presence of TF triggered coagulation through PS exposure, we found that sunitinib delayed and decreased fibrin formation.
Next, we tested the effects platelet inhibition by aspirin in combination with sunitinib. This resulted in a further reduction (±75%) of GPVI-dependent platelet aggregation, when compared to sunitinib alone. Moreover, addition of sunitinib to blood from aspirin-treated healthy volunteers further reduced thrombus formation and PS exposure (by 30% and 50% respectively) on collagen under flow both in the presence and absence of coagulation.
Conclusions: Sunitinib treatment suppresses GPVI-induced platelet procoagulant activity and ensuing fibrin formation. This effect is enhanced by additional treatment with aspirin. These results ask for awareness among clinicians for the combined antiplatelet effects of TKIs together with aspirin.
To cite this abstract in AMA style:Tullemans BME, Fernández DI, Veninga A, Aarts MJB, van der Meijden PEJ, Heemskerk JWM, Kuijpers MJE. Tyrosine Kinase Inhibitor Sunitinib Delays Platelet-induced Coagulation: Additive Effects of Aspirin [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/tyrosine-kinase-inhibitor-sunitinib-delays-platelet-induced-coagulation-additive-effects-of-aspirin/. Accessed October 1, 2023.
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