Abstract Number: LPB0121
Meeting: ISTH 2021 Congress
Background: Tyrosine kinase inhibitors (TKIs), such as sunitinib, are used for cancer treatment, but may also affect platelet count and function with possible hemostatic consequences.
Aims: We investigated how patient treatment with the TKI sunitinib affected quantitative and qualitative platelet traits as a function of the sunitinib level and the occurrence of bleeding.
Methods: The study was approved by the medical ethical committee of Maastricht University Medical Center+ (MUMC+) and full informed consent was obtained from all participants. Blood was collected from 20 metastatic renal cell carcinoma (mRCC) patients before treatment, and at 2 weeks, 4 weeks and 3 months after sunitinib administration. We measured blood cell counts, platelet aggregation, and the concentrations of sunitinib, as well as its N-desethyl metabolite, in plasma, serum and isolated platelets. Progression of disease (PD) and bleeding were monitored after 3 months.
Results: In sunitinib-treated mRCC patients, concentrations of (N-desethyl)sunitinib in plasma and serum were highly correlated. In the patients’ platelets the active metabolite levels was relatively increased as compared to sunitinib. On average, a continued reduction in platelet count was observed on-treatment, which was significantly related to the inhibitor levels in plasma/serum. Principal component and correlational analysis showed that the (N-desethyl)sunitinib levels in plasma/serum were linked to a reduction in both platelet count and collagen-induced platelet aggregation. The reduced aggregation was in part associated with reported bleeding, but did not correlate to PD.
Conclusions: The sunitinib-induced reduction in quantitative and qualitative platelet traits may reflect the effective sunitinib levels in the patient. These results may serve as a proof-of-principle for other TKI-related drugs, where both platelet count and functions are affected, which could be used for dose adjustments.
This work was funded by Pfizer as an Investigator-Initiated Research grant to M.J.E.K. (Tracking Number WI209458).
To cite this abstract in AMA style:Tullemans BM, Brouns SL, Swieringa F, Sabrkhany S, van den Berkmortel FW, Peters NA, de Bruijn P, Koolen SL, Heemskerk JW, Aarts MJ, Kuijpers MJ. Quantitative and Qualitative Changes in Platelet Traits of Sunitinib-treated Patients with Renal Cell Carcinoma in Relation to Circulating Sunitinib Levels: A Proof-of-Concept Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/quantitative-and-qualitative-changes-in-platelet-traits-of-sunitinib-treated-patients-with-renal-cell-carcinoma-in-relation-to-circulating-sunitinib-levels-a-proof-of-concept-study/. Accessed November 27, 2021.
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