The Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis

Widely viewed as an enigmatic disease, adenomyosis is a common gynecological disease with bewildering pathogenesis and pathophysiology. One defining hallmark of adenomyotic lesions is cyclic bleeding as in eutopic endometrium, yet bleeding is a quintessential trademark of tissue injury, which is invariably followed by tissue repair. Consequently, adenomyotic lesions resemble wounds. Following each bleeding episode, adenomyotic lesions undergo tissue repair, and, as such, platelets are the first responder that heralds the subsequent tissue repair. This repeated tissue injury and repair (ReTIAR) would elicit several key molecular events crucial for lesional progression, eventually leading to lesional fibrosis. Platelets interact with adenomyotic cells and actively participate in these events, promoting the lesional progression and fibrogenesis. Lesional fibrosis may also be propagated into their neighboring endometrial-myometrial interface and then to eutopic endometrium, impairing endometrial repair and causing heavy menstrual bleeding. Moreover, lesional progression may result in hyperinnervation and an enlarged uterus. In this review, the role of platelets in the pathogenesis, progression, and pathophysiology is reviewed, along with the therapeutic implication. In addition, I shall demonstrate how the notion of ReTIAR provides a much needed framework to tether to and piece together many seemingly unrelated findings and how it helps to make useful predictions.