Platelets are one of the most important components for homeostasis and health, even if they rarely receive the recognition they deserve.
“Platelets are the primary cellular mediators of hemostasis and this function firmly acquaints them with a variety of inflammatory processes,” Maouia and colleagues wrote in Transfusion Medicine Reviews.
The primary purpose of platelets is to respond to vascular damage and to signal to leucocytes to arrive at sites of injury. This primary function of platelets is the reason that platelet count is routinely included in blood analysis.
Interestingly, recent research has revealed that platelets have a number of important functions in protecting the body against foreign bodies. For example, platelets have been discovered to be capable of binding to pathogens directly via the expression of pathogen-associated molecular pattern (PAMP).
In addition, platelets play a significant role in the innate immunity by expressing a range of functional immune receptors; these receptors interact with immune cells at the vascular endothelium. The unique properties of platelets allow them to form platelet-leukocyte aggregates that are capable of immobilizing pathogens.
“How platelets possess all their different immune functions is unknown,” Maouia and colleagues wrote. “One theory suggests an evolutionary link between platelets and invertebrate hemocytes, which not only protect arthropods from pathogens but also clot hemolymph at sites of exoskeletal breach; perhaps a divergence occurred during platelet evolution where they retained some of the immune properties of the hemocyte.”
Scientific research has firmly established that platelets are in constant, close interaction with infectious agents, as well as in native and adaptive immune system cells. Platelets are able to achieve this because they contain a wide range of pro- and anti-inflammatory molecules. It is for this reason that scientists are increasingly advocating for platelets to be recognized as critical components of the immune system.
Platelet Activation in Idiopathic Thrombocytopenic Purpura
Idiopathic thrombocytopenic purpura (ITP) is characterized as an isolated thrombocytopenic autoimmune disorder of unknown etiology. It is mainly characterized by marked low platelet count, less than 100 x 109 L.
The common presentation of patients with this disease is a reduced quality of life, driven by excessive feelings of fatigue. Patients may also present with bruise-like rashes or mild mucocutaneous bleeds, and around 5% of patients experience severe bleeds. Nevertheless, a subsection of individuals remain asymptomatic and do not experience bleeding episodes.
Read more about idiopathic thrombocytopenic purpura etiology
Due to the low platelet count in patients with ITP, the risk of venous thromboembolism is ever-present, with some studies suggesting that patients with ITP are twice as likely to experience these episodes compared to the general population.
One of the hallmarks of ITP is the production of autoantibodies, especially antibodies belonging to the class of immunoglobulin G. The detection of immunoglobulin G is widely considered a pathogenic indication of ITP.
It should be noted that the failure to detect these autoantibodies does not rule out ITP. Rather, a number of other mechanisms have been known to also contribute to ITP pathophysiology. These include megakaryocyte inhibition, cytotoxic T-cell mediated platelet destruction, as well the formation of microthrombus as a result of platelet activation by auto-antibodies.
The reduction of platelets in ITP can be due to one of two (or a combination of both) factors: either platelet production is low, or platelets are being removed from the peripheral circulation at abnormally high rates. Crucially, antiplatelet antibodies are detected in around half of the patients with ITP.
It has been observed that antiplatelet autoantibodies can trigger the classical complement pathway in some patients with ITP. Studies suggest that antibody-mediated complement fixtures can result in platelets shedding from extracellular vesicles. A combination of complement activation by antibody-coated platelets and the formation of vesicles is thought to drive thrombosis in ITP.
Understanding the Central Role of Platelets
“Platelets, the main players of hemostasis and thrombosis, have multiple regulating properties linking immune, complement, and coagulation systems,” Sun and colleagues wrote in Cells.
Let’s delve a little deeper into the role that platelets play in regulating homeostasis. Studies indicate that active platelets play a significant role in modulating the function of the innate and adaptive immune systems; they do this by releasing a number of pro-inflammatory and immune mediators that directly interact with immune cells.
Read more about idiopathic thrombocytopenic purpura treatment
In other words, platelets play a major role in immune function; continued research on these properties may yet yield data that can transform the care of individuals with platelet pathology. This invites the entire medical community to consider the role that platelets play beyond stopping hemorrhage, and consider the role they may play in strengthening immune processes.
“On the other hand, the roles of platelets and of platelet activation processes in these autoimmune diseases are still only partly understood,” Sun et al wrote. “The interactions between platelets with other immune cells such as B and T cells, macrophages and leukocytes require further clarification. We foresee that better understanding of the role of platelets will reveal new therapeutic options in the future.”
References
Maouia A, Rebetz J, Kapur R, Semple JW. The immune nature of platelets revisited. Transfus Med Rev. Published online December 9, 2020. doi:10.1016/j.tmrv.2020.09.005
Sun S, Urbanus RT, Ten Cate H, et al. Platelet activation mechanisms and consequences of immune thrombocytopenia. Cells. Published online December 1, 2021. doi:10.3390/cells10123386
