Thrombocytosis in cancer patients: when more is not better-in fact, the opposite.

Abstract

Platelets are key elements of hemostasis which play an important role in pathological processes, especially in the context of cancer. They are small, disc-shaped structures equipped with a rich network of organelles and a cytoskeleton. In healthy individuals, the range of the platelet count is 150-350*103/uL. They contain numerous receptors that are responsible for diverse cellular responses triggered by physiological and pathological signals. The process of their production, known as thrombopoiesis, is regulated by many factors, which allows stem cells to transform into megakaryocytes and facilitates further platelet production. In the context of cancer, platelets play a special role in thrombosis, which is a common complication in cancer patients. Moreover, through the cytokines and adhesion molecules they secrete, cancers affect platelets, increasing their prothrombotic potential. Chemotherapy and radiotherapy can also damage blood vessels, promoting thrombosis. Platelets also support the process of cancer metastasis, affecting different stages of its evolution. By forming aggregates with cancer cells and leukocytes, they protect cancer cells from mechanical forces in the bloodstream and from recognition by the immune system. In addition, platelets secrete growth factors such as PDGF and TGF-β, which support cancer cell proliferation and angiogenesis, which in turn stimulates further tumor development. Leukocytes, enter into cooperation with platelets, supporting the adhesion of cancer cells to the vascular endothelium and facilitating their migration to distant tissues. A high platelet count is an unfavorable prognostic factor in many cancers, associated with poorer survival rates, a greater tendency to form metastases, and lower efficacy of anticancer treatment. Thrombocytosis is also associated with an increased risk of thrombotic complications in cancer patients, which requires intensive monitoring and antithrombotic prophylaxis. Platelets can also increase the resistance of cancer cells to chemotherapy and radiotherapy by supporting DNA repair in damaged cancer cells and protecting them from cytotoxic drugs. Surface receptors such as P-selectin and GP IIb/IIIa, facilitate platelets in forming aggregates with CTCs, which enhances their survival and promotes the formation of metastases. Intensive research is underway concerning the possibility of using antiplatelet therapy, such as the use of aspirin or P2Y12 receptor inhibitors, as potential methods for treating cancer patients. Some studies have shown that aspirin can prevent the formation of pre-metastatic niches, and P2Y12 inhibitors, such as clopidogrel, reduce the incidence of metastases in animal models. In addition, platelet apheresis is gaining importance as a therapeutic method in cancer, particularly in the case of thrombocytosis. In summary, platelets play an important role not only in hemostasis, but also in the development and progression of cancer, which makes them an important target in the context of both antithrombotic and anticancer therapy. Their activity and number affect the course of the disease, the response to treatment and the risk of thrombotic complications, which emphasizes the need for further research on their role in oncology.