Platelets (or thrombocytes) are tiny blood cells that help our body to form clots to stop bleeding! Platelets are pretty important for normal haemostasis (arrest of bleeding), without platelets we’d bleed out from the smallest of injuries [1, 2].
Max Schultze in 1865 first described platelets as “spherules” which he noted were much smaller than RBCs, sometimes clumped and found in fibrin material. Little did he know what these “spherules” were, it wasn’t until 1882 whereby Giulio Bizzozero described platelets as ‘little plates’ which overtime became to be known as ‘platelets’. Bizzozero went on to identify their function in coagulation and has been pivotal in our understanding of platelets through use of the microscope .
Platelet production [2}:
Platelets are produced by very large cells in the bone marrow called megakaryocytes. As megakaryocytes develop into larger cells they undergo fragmentation that results in the release of platelets. Once platelets are made and circulated into our blood stream they live for 8-10 days. Our bodies usually contain a lot of platelets, the normal platelet count ranges from 150,000-450,000 platelets per micro-litre of blood .
Platelet activation [4, 5]:
During vascular injury, blood vessels get damaged which sends out a signal to the platelets. The platelets are then drawn to the site of injury and through a series of tightly regulated cell signalling processes they become active, change shape to form tentacle-like protrusions, spread across the injury surface and aggregate together. In combination with clotting factors, platelets help to form a blood clot that is stable until wound healing has occurred. It’s the cooperation of platelets, cells of the endothelium and clotting factors that prevent us from bleeding out when we injure ourselves. Platelet activation is an extremely important process in haemostasis! [4, 5]In incidences such as cardiovascular disease we get unwanted platelet activation, this is where platelets can become activated without vascular injury, which can be a result of issues in platelet activation and/or platelet inhibition, as well as atherosclerosis and inflammation.
Platelet inhibition [6, 7, 8]:
Under normal circumstances to prevent spontaneous platelet activation, platelets are tightly regulated by inhibitors released from the endothelium. The endothelial cells produce naturally occurring inhibitors such as prostacyclin and nitric oxide to maintain the quiescent (resting) state of platelets in circulation. Prostacyclin and nitric oxide are constantly released by the endothelium in a manner that maintains platelets in an inactive state but while still allowing platelets to activate during vascular injury.
Prostacyclin once bound to it’s IP receptor on the surface of platelets causes the activation of g-protein coupled receptors, which in turn activate adenylyl cyclases. Adenlyl cyclases are transmembrane proteins, once activated they lead to the production of cyclic adenosine monophosphate (cAMP). The intracellular concentration of cAMP increases and this then leads to the activation of protein kinase A (PKA). Kinases phosphorylate proteins, therefore the activation of PKA leads to the phosphorylation of proteins that ultimately lead to platelet inhibition. Nitric oxide works in a very similar fashion. Nitric oxide is cell permeable so doesn’t require a receptor like prostacyclin. Once inside the cell, NO activates guanylyl cyclases (GCs) which leads to the production of cyclic guanosine monophosphate (cGMP). Cyclic GMP, just like cAMP, goes on to activate protein kinases, in the case it activates protein kinase G (PKG). Protein kinase G then phosphorylates proteins that contribute to the inhibition of platelets .
The regulation of platelets in circulation is a strict balance between activation and inhibition. Platelets need to be inhibited enough to prevent spontaneous activation but not so much that they can’t activate during vascular injury. It’s a perfect example of how tightly controlled cell signalling processes in our bodies actually are, without this balance we could be at risk of spontaneous clotting or bleeding out from small injuries.
Platelet disorders :
Thrombocytopenia is a condition where the bone marrow makes too few platelets or the platelets are destroyed. If the platelet count becomes too low, bleeding can occur under the skin and can be seen as bruise or it can happen inside the body as internal bleeding. It can also happen outside the body through an injury that won’t stop bleeding. Thrombocytopenia can be caused by many conditions including several medicines, cancer, liver disease, pregnancy, infection and abnormal immune system.
Essential thrombocythemia is a condition where the bone marrow produces too many platelets. Those with this condition have platelet counts of over 1 million, which is a lot of platelets. Symptoms include the formation of blood clots which can potentially block blood supply to the brain oor heart. It has been said that the cause of this is yet to be determined.
Secondary thrombocytosis is another condition whereby there are too many platelets, however this condition is much more common. In this case, it is caused by another disease or condition which causes the bone marrow to produce more platelets. The causes include, infection, inflammation, certain types of cancer and sometimes reaction to medicines. The symptoms are usually not serious and the platelet count usually returns to normal once the original condition is treated.
Platelet dysfunction is a condition where the platelet count is normal but the platelets do not work as they should. Many rare diseases can be linked to poor platelet function. Medicines such as Aspirin can cause, which is why in some cases such as cardiovascular disease, Aspirin is used to reduce platelet activation. It’s important to know how medicines can affect platelets, as taking certain medications that result in platelet dysfunction can increase the risk of bleeding.
Thanks so much for reading, I hope you enjoyed this post!
Do you use platelets in your research? Let me know in the comments, I’d love to hear from you!
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 Brewer, D.B. (2006), Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. British Journal of Haematology, 133: 251-258. https://doi.org/10.1111/j.1365-2141.2006.06036.x
 Jonathan M. Gibbins. Journal of Cell Science 2004 117: 3415-3425; doi: 10.1242/jcs.01325
 Brass LF. Thrombin and platelet activation. Chest. 2003 Sep;124(3 Suppl):18S-25S. doi: 10.1378/chest.124.3_suppl.18s. PMID: 12970120.
 Moncada S. Prostacyclin and arterial-wall biology. Arteriosclerosis. 1982; 2: 193-207. doi: 10.1161/01.ATV.2.3.193
 Moncada, S., Gryglewski, R., Bunting, S. et al. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263, 663–665 (1976). https://doi.org/10.1038/263663a0
 Fukumoto S, Koyama H, Hosoi M, Yamakawa K, Tanaka S, Morii H, Nishizawa Y. Distinct role of cAMP and cGMP in the cell cycle control of vascular smooth muscle cells: cGMP delays cell cycle transition through suppression of cyclin D1 and cyclin-dependent kinase 4 activation. Circ Res. 1999 Nov 26;85(11):985-91. doi: 10.1161/01.res.85.11.985. PMID: 10571528.