Abstract
Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro, in vivo, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.
Highlights
Circulating anucleate cytoplasmic fragments of megakaryocytes, platelets play critical and well-characterized roles in wound healing and maintenance of vascular integrity by adhering, activating, and aggregating at sites of vascular injury to form blood clots and stop bleeding [1]
The mechanisms underlying associations between paraneoplastic thrombocytosis and cancer progression have yet to be fully elucidated, there is strong evidence for reciprocal interactions between tumor growth and platelet production and activation; accumulating data suggest that platelets are a biomarker of disease burden, with increased levels at diagnosis falling after primary treatment and again rising at recurrence, and actively contribute to disease progression [19,20]
In a study of 179 women in Korea with advanced stage (III and IV) disease, thrombocytosis based on measurements from up to 7 days prior to diagnosis was associated with approximately three-fold worse overall survival (OS), even after adjustment for tumor histology, platelet count following chemotherapy, and CA-125 following primary chemotherapy [33]
Summary
Circulating anucleate cytoplasmic fragments of megakaryocytes, platelets play critical and well-characterized roles in wound healing and maintenance of vascular integrity by adhering, activating, and aggregating at sites of vascular injury to form blood clots and stop bleeding [1]. Thrombocytosis has been demonstrated to be a prognostic factor for multiple outcomes in numerous studies (Table 1) with significant associations from both univariate and multivariate analyses, suggesting independent associations with disease outcomes. The mechanisms behind these associations are under investigation; therapeutics with anti-platelet activity, such as non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, have been associated with better prognosis in epidemiologic studies, and anti-platelet therapies are being investigated in the ovarian cancer clinical setting [40,41,42,43].
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