In this section we will cover:
Platelets are small cells that circulate in the blood. They are involved in the formation of blood clots and the repair of damaged blood vessels.
When a blood vessel is injured, platelets stick to the damaged area and spread along the surface to stop the bleeding (this process is called adhesion). At the same time, chemical signals are released from small sacks inside the platelets called granules (this process is called secretion). These chemicals attract other platelets to the site of the injury and make them clump together to form what is called a platelet plug (this process is called aggregation).
Sometimes the platelet plug is enough to stop the bleeding. However, if the wound is large, other proteins called clotting factors are recruited to the site of the injury. These clotting factors work together on the surface of the platelets to form and strengthen the blood clot.
What are platelet function disorders?
Platelet function disorders are conditions in which platelets do not work the way they should, resulting in a tendency to bleed or bruise. Since the platelet plug does not form properly, bleeding can continue for longer than normal.
Since platelets have many roles in blood clotting, platelet function disorders can lead to bleeding disorders of various intensities.
Types of platelet disorders
There are three different types of platelets disorders:
Bernard-Soulier syndrome is a platelet function disorder caused by an abnormality in the genes for glycoprotein Ib/IX/V. These genes code for a group of linked proteins normally found on the surface of platelets, the glycoprotein Ib/IX/V receptor (also called the von Willebrand factor or VWF receptor). Because this receptor is absent or is not working properly, platelets do not stick to the injured blood vessel wall the way they should and it is difficult for the normal blood clot to form.
Glanzmann thrombasthenia is a platelet function disorder that is caused by an abnormality in the genes for glycoproteins IIb/IIIa. These genes code for a group of linked proteins normally found on the surface of platelets, the glycoprotein IIb/IIIa receptor (also called the fibrinogen receptor). Because this receptor is absent or is not working properly, platelets do not stick to each other at the site of injury and it is difficult for the normal blood clot to form.
Storage pool deficiencies are a group of disorders caused by problems with platelet granules. Granules are little sacs inside the platelet in which proteins and other chemicals important to its function are stored. There are two types of granules: alpha granules and dense granules.
Some storage pool deficiencies are caused by a lack of granules, but the most common ones are caused by a failure of the platelets to empty the contents of the granules into the bloodstream (this is called the secretory or release mechanism).
- Release defects are a diverse group of disorders caused by a problem with the secretory mechanism. Even though the granules are present within the platelets, their contents are not emptied into the bloodstream properly.
- Delta storage pool deficiency is a platelet function disorder caused by a lack of dense granules and the chemicals normally stored inside them. Without these chemicals, platelets are not activated properly and the injured blood vessel does not constrict to help stop bleeding. This type of bleeding problem can be a feature of other inherited conditions (such as Hermansky-Pudlak syndrome and Chediak-Higashi syndrome).
- Grey platelet syndrome is a very rare platelet function disorder caused by a lack of alpha granules and the chemicals normally stored inside them. Without these proteins, platelets cannot stick to the blood vessel wall, clump together the way they should, or repair the injured blood vessel.
Resources:
More information about platelet function disorders can be found via the following websites and documents:
World Federation of Hemophilia
Adapted from the World Federation of Hemophilia website
Jim is aged 66 and has Haemophilia A with a high titer inhibitor which he developed at age 14.
Maria Elisa Mancuso (MD, PhD) is a Haematologist and works as a Senior Haematology Consultant at the Center for Thrombosis and Haemorrhagic Diseases of IRCCS Humanitas Research Hospital in Rozzano, Milan, Italy. She is Adjunct Clinical Professor at Humanitas University. She obtained a post-degree in Clinical and Experimental Haematology and a PhD in Clinical Methodology. She is involved in clinical research and has published several original articles in peer-reviewed journals a The Lancet, Blood, Journal of Thrombosis and Haemostasis, Haematologica, Thrombosis and Haemostasis, British Journal of Haematology and Haemophilia. She is reviewer for several peer-reviewed journals and member of the Editorial Board of JTH. She is a member of several scientific societies (ISTH, WFH, ASH, EAHAD, SISET, AICE) and was a medical member of the Inhibitor Working Group of the European Hemophilia Consortium. She is co-chair of the ADVANCE Study Group. She has acted also as co-chair of the Scientific and Standardization Subcommittee of ISTH on FVIII, FIX and rare bleeding disorders. She has been involved as principal and co-investigator in several clinical trials, and she takes care of both children and adults with hemophilia and other congenital bleeding disorders with a specific scientific interest in novel therapies, prophylaxis, inhibitors, and chronic hepatitis C.
As a patient with factor II deficiency, the diagnostic and treatment of rare bleeding disorders is a matter dear to my heart. My motivation to participate in the work of the ERIN committee is to improve both diagnostic and treatment for patients with rare bleeding disorders across Europe.
Economist and financial expert by profession, executive coach and trainer by passion and haemophilia advocate by every drop of my blood through my son (who has severe haemophilia A with inhibitors). Bringing a good decade of practical experience from the corporate insurance world, laser focus, growth mindset and resilience from my own experience, offering you anything I can just do, in hope that together we can make life more fulfilled for those impacted by bleeding disorders.
Amy Owen-Wyard is a Registered Mental Health Nurse. With experience working with children, young people, their families and adults with severe and enduring mental health conditions. Amy was also involved in a service improvement to provide a holistic care approach for those in general hospitals to support both their mental and physical health, whilst sharing her expertise and knowledge in mental health with the wider multidisciplinary team.
