Every year on 17 April, World Haemophilia Day is recognised worldwide to raise awareness of haemophilia, von Willebrand Disease, and other inherited bleeding disorders. From his early days in lecture halls to his current work in research labs, Dr. Tom McKinnon, Senior Lecturer in the Department of Immunology and Inflammation, shares his expertise. He unravels the complexities of Von Willebrand factor (VWF), advocating for greater awareness of this commonly misunderstood condition.
I can vividly recall an early morning undergraduate lecture I attended over 20 years ago now (has it really been that long?!). In a slightly hungover state, I listened to the lecturer describe a protein that helps blood cells stick together (clot) when you bleed called Von Willebrand Factor and Von Willebrand’s disease – a common inherited condition that can make you bleed more easily than normal. At the time, I didn’t think much about it, but two years and a BSc later, I found myself at Imperial undertaking a PhD investigating the structure and function of VWF, beginning my scientific journey into the world of the largest protein found in the blood, and in my humble opinion, the most fascinating.
Circulating around the body, VWF is like a giant molecular ball of string that responds to the force of blood flow. When we damage our blood vessels, this ball of string sticks to the damage site, and unwinds and begins to capture platelets that are speeding past, thereby limiting blood loss.
When people ask me what I research and I say “VWF and VWD,” I’m often met with a blank expression. I’ll explain that VWF helps blood to clot properly and if you don’t have enough of it or your VWF doesn’t work properly, you might bleed. Interestingly, after I mention bleeding, the response is often, “Oh, just like haemophilia.” While haemophilia is probably the best-known bleeding disorders, perhaps in part due to its royal links, VWD is generally not on the tip of the tongue. Conversely, VWD is more common than haemophilia. Indeed, it’s the most common inherited bleeding disorder worldwide with an estimated prevalence of 2%, possibly even higher. Despite this, awareness of VWD is relatively low. At the primary care level, VWD is generally not the first thought that springs to mind when a patient presents with bleeding, yet it is certainly a common cause and quite easy to test for and treating VWD is relatively simple.
Although we maybe take this for granted. As a scientist I am interested in the nitty gritty of how the protein operates at the molecule level, with my lab often looking at how VWD causing mutations impact VWF function. I recall several years ago reading a case report from Cameroon about a novel mutation. Upon enthusiastically emailing the lead author of the study to ask if he would like us to make and characterise the mutant VWF protein for him, he bluntly replied: “If you like, but more urgently, could you send us something to treat her (the patient) with.” A sobering thought that in parts of the world, an easily treatable disorder cannot be treated due to lack of resources.
As research improves our understanding of VWF – turns out it’s a pretty complex molecule that is also a good anti-thrombotic (an agent that prevents the formation of blood clots) target and it may well have wider roles aside from capturing platelets – VWD is not going away. Yet for such a common disorder and possibly the cause of so many bleeding episodes, especially in women who are more likely to notice excessive bleeding, we are allowing VWD to hide in plain sight. Bleeding of any sort should never be taboo and should be open for discussion, with VWF and VWD certainly part of that.