Platelet function beyond hemostasis and thrombosis

Abstract

Purpose of review The platelet paradigm that is well established in hemostasis and thrombosis can be extended to other disease states. A consideration for some major health issues, such as inflammation, cancer, infection, and neuroscience and how platelet function impacts the pathophysiology of each clinical situation is provided. Recent findings Decades of research and knowledge of platelet function exists and the same is true for inflammation and cancer. The literature is full of platelet biology overlapping into other, non-thrombotic, disease states. However, major gaps exist that prevent a complete mechanistic understanding of platelet function in these other diseases. While much of the overlap provides antidotal relationships, future studies will likely uncover novel pathophysiological pathways that are highly relevant to human diseases. Summary Recent findings in four major disease areas, inflammation, cancer, infection and neuroscience are described with current literature linking the disease to platelet function. The availability of anti-platelet therapies, such as aspirin, exist and future consideration can be given as to whether anti-platelet therapy is potentially beneficial or harmful as mechanisms of platelet involvement are better defined.

RASA3 is a critical inhibitor of RAP1-dependent platelet activation

“…Mammalian platelets are small anucleated blood cells specialized to continuously monitor and preserve the integrity of the cardiovascular system (hemostasis) (1)(2)(3). Once released from megakaryocytes, they circulate for 10 days in human blood and 5 days in mouse blood.…”

The platelet P2 receptors in inflammation

“…Conclusion: These data strongly suggest that P2Y 12 may represent an important pharmacological target for the treatment of patients with allergic bronchial asthma. Platelets play a well established role in haemostasis and thrombosis, but also have inflammatory functions, influence innate and adaptive immune responses, play a role in tumorigenesis, cancer growth and dissemination (1)(2)(3)(4)(5).…”

“…Platelets express toll-like receptors, which initiate the innate immune response. Moreover, they interact with activated endothelium, undergo chemotaxis,"prime" leukocytes for efficient tissue recruitment, activate other inflammatory cells, exert phagocytosis, release biologically active substances, including adhesive proteins, vasoactive and proinflammatory mediators (1)(2)(3)(4)(5). Major platelet-derived chemokines and cytokines include PF4/CXCL4, pro-platelet basic protein (ppbp), RANTES, inorganic polyphosphate and IL-1β, among a large number of inflammatory molecules (6)(7)(8).…”

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

“…However, during the last decade, other functions beyond aggregation have been proposed [41,42]. Although anucleate, platelets contain mRNAs and are capable of de novo protein synthesis [43].…”

“…However, it is unknown whether these mediators recruit specific leukocyte subtypes. Moreover, recent studies indicate that platelets may also recognize microbial pathogens through TLRs, thus actively participating to the immune response [41,42,49].…”