What Is Von Willebrand Disease?

Overview

Von Willebrand Disease (VWD) is a form of haemophilia. ‘Haemophilia’ comes from the ancient Greek for an ‘attraction to’ or ‘love’ of ‘bleeding’, and fundamentally describes a collection of diseases which are linked to difficulties in forming blood clots. This leads to excessive or inappropriate bleeding.  

A variety of bleeding conditions have been described throughout history, yet it is only in recent times that we have been able to delve deeper into their underlying causes. Von Willebrand's disease is no different. This disease was first noted by the Finnish physician, Erik Von Willebrand back in 1926.¹ Von Willebrand noticed patterns of easy bleeding within families and hypothesised that there was a relationship and explanation for this. Fast-forwarding to today, our ever-advancing diagnostic technology has allowed us to understand more about VWD, including its different variants and their specific nuances. 

Von Willebrand's Disease is linked to a faulty gene that is usually passed down from generation to generation. It is understood to be the most commonly inherited type of haemophilia and affects approximately 1% of the population. This prevalence of VWD results from its ‘dominant’ inheritance pattern - meaning that if 1 of your parents has VWD, there is a 50% chance you will get it too. However, it is also possible to ‘acquire’ VWD as a result of other conditions.² This is different to classic haemophilia (haemophilia A), which only appears fully in males carrying the defective gene.^1,2,3 

Causes of von willebrand disease

In healthy individuals, blood clotting is crucial in protecting your body from insult and injury.^2,3 There are several different components found within your blood that are involved in healthy blood clotting, which is called haemostasis.³ Haemostasis describes the ability of your body to form a clot in response to blood vessel injury and bleeding and aims to prevent blood loss whilst initiating the healing process. However, these normal clotting mechanisms are disrupted in VWD, meaning that your body may bleed inappropriately or excessively.^2,3 

Specifically, two important blood constituents are affected by VWD: Von Willebrand Factor (VWF) and Factor VIII (FVIII). In healthy individuals, VWF and FVIII are joined together and circulate in your blood until they are needed.^2,3,4,5 When an injury occurs, these clotting factors separate and become free to bind to a variety of other blood components or parts of the blood vessel.^2-5 Together, these factors and components form blood clots, which plug the holes in blood vessels.^2-6 The hallmark sign of VWD is a reduction in the levels and/or efficiency of VWF, which both negatively affects your ability to form blood clots and heal injuries.^2,6 

Types of von willebrand disease

There are three different types of VWD: Type 1, Type 2, and Type 3. These differ in terms of their molecular and cellular characteristics and how much they increase your risk of inappropriate bleeding. Other types of VWD include acquired VWD, platelet-type ‘pseudo’ VWD, and ‘reduced VWF’ disease. However, these do not fit into the typical ‘box’ of VWD and will not be covered in this article.² 

Type 1: Type 1 is the most common type of Von Willebrand Disease and makes up around 75% of cases. This type of VWD results from reduced levels of VWF and/or FVIII and is often deemed ‘mild’ in terms of bleeding risk. 

Type 2: Type 2 Von Willebrand Disease makes up most of the remainder of cases (~25%) and is split up further into the sub-categories: 2A, 2B, 2M, or 2N. Type 2 VWD affects the ability of VWF to bind to other blood components and clotting factors, affecting its ability to form stable clots and prevent bleeding. Type 2B is commonly regarded as the most concerning type of VWD.⁷ 

Type 3: This type is linked to severe reductions in the levels of VWF. In some cases, there is a complete absence of VWF. This is the rarest form of the disease and affects very few people, yet is unfortunately associated with the worst risk of bleeding.  

Signs and symptoms of von willebrand disease

• Nosebleeds (epistaxis)
• Heavy periods
• Bleeding for longer than usual from minor cuts/wounds
• Bleeding into your joints, which may cause them to become swollen and painful 
• Bruising easily

Diagnosis

Diagnosing VWD involves a number of blood tests, which enable doctors to take a deeper look at the components that make up your blood. Specific blood tests will be used to differentiate the type of Von Willebrand disease. These blood tests aim to diagnose you with a specific type of VWD by measuring your levels of VWF, as well as how well it binds to other components within your blood. This is crucial, as it will ensure you are offered suitable treatments.^2,3,4,5,7

The blood tests used to diagnose specific types of VWD include:^2,3,4,7,8

• VWF: Ag - this test is used to measure levels of VWF in the blood. VWF levels <0.3 iu/ml are deemed sufficient for a definitive diagnosis of VWD, regardless of your history of bleeding.
• FVIII: C - this test is used to measure the binding activity of FVIII, which is normally bound to VWF.
• VWF: RCo - this tests how well VWF binds to an antibiotic called Ristocetin. This indicates how well VWF would bind to the factor GPIbα, which is involved in the clotting process.
• VWF: CB - this test measures how well VWF binds to a protein called collagen. This helps identify defects in VWF and can be used to diagnose type 2A or 2B VWD.
• LD-RIPA - this tests the interaction of your blood sample with a low dose of Ristocetin. If your blood shows a hyperactivity response to the Ristocetin, you may have VWD Type 2B or a ‘platelet’ pseudo-VWD variant. 

As well as these blood tests, it is important that your doctor takes a thorough account of your medical and bleeding history. This may involve noting times you have bled unexpectedly, such as from blowing your nose or brushing your teeth. Your doctor may also ask you to keep a record of how frequently and how severely these symptoms occur.^2,3,4,7

Lastly, genetic testing may sometimes be recommended in the diagnosis of some cases of VWD, specifically allowing your medical team to differentiate between type 2 variants of VWD. Genetic testing may also be offered to patients wishing to have children to help inform their choices.^2,3,4,7   

Diagnosing VWD can be difficult, and the major concern is in inadvertently diagnosing someone as having VWD, where there may be other causes for bleeding.^2,3,4,7 Your medical team will need to be proactive in suspecting and investigating other potential reasons for your bleeding. Additionally, the levels of VWF in your blood may fluctuate day-to-day, meaning that at least 2 separate blood tests confirming low levels of VWF will be needed for a confident diagnosis to be made.^2,3,4 

Management and treatment of von willebrand disease

In most cases, your treatment will involve strategies to reduce the risk of a bleeding event.^2,3,5 This may be achieved by the use of medications or by replacement blood products/factors.^2,3,5 However, treatment will be tailored to your specific needs, taking into consideration both your type of VWD and the aims of your treatment.^2,3,5 For example, using the wrong medication to treat Type 2B VWD could actually lead to more harm and further increase the risk of bleeding.^2,3,5

Prophylactic treatments:

Desmopressin – Desmopressin is a potential option for those with Type 1 and some Type 2 patients. A confirmed diagnosis of which type of VWD will be needed prior to its administration. Desmopressin is not recommended for Type 2B or Type 3 VWD, as it can increase the risk of bleeding.^2,3,5 Individuals with Type 1 VWD normally respond positively to desmopressin, but a trial dose may be required to see if desmopressin is a suitable option for you.^2,3,5 Depending on your response to the trial dose, you may be given the medication to take as and when needed via a nasal spray or an injection. You should not take desmopressin if you have, or at risk of, atherosclerosis.⁹ 

Tranexamic acid – This medication works by preventing the breakdown of fibrin, a major structural component of blood clots. This reinforces the clot’s structure and makes bleeding less likely to occur. Tranexamic acid can be taken as a tablet before or during times of expected bleeding, for example, either during your menstrual period or before receiving any dental treatment.^10,11 Tranexamic acid is not suitable for urinary tract bleeding. 

The treatment of active bleeding will depend on how severe your symptoms are and how much of a risk your bleeding poses to your health. In cases of severe bleeding or cases where the above options are not appropriate, you may also be offered replacement blood products, fluids, or clotting factors such as Von Willebrand Factor or Factor VIII.^2,3,5,12 These will be given via a drip in your arm and aim to top up the essential parts of your blood that may be lost during a bleeding event, as well as to maintain a healthy level of circulating blood.^5,12

Other supportive treatments may also be used in those frequently experiencing bleeding:

• Iron replacement may be used in cases where repeated bleeding episodes lead to anaemia. You may be offered a daily supplement (in the form of tablets) or a one-off injection to boost your levels of iron.³ 
• Combined oral contraceptive pill – hormonal contraceptive pills may be used in women who are experiencing blood loss from heavy periods. This pill helps to regulate your menstrual cycle and hopefully reduce the severity of bleeding, or in cases where you take the pill continuously, it may completely prevent menstrual bleeding altogether.  

Complications of von willebrand disease

The main complication of this condition is bleeding. The cause of bleeding incidents may vary considerably and can range from light bleeding whilst blowing your nose or brushing your teeth to major haemorrhaging within your gut. Individuals who experience menstrual bleeding may have heavier cycles than usual, and although the ramifications of such bleeding events may first appear non-severe, repeated bleeding in any form may impact your daily life and be being both distressing and inconvenient. 

As touched on earlier, severe bleeding episodes may be catastrophic and even life-threatening.¹¹ Major bleeding may lead to fatal blood loss, shock, and cardiovascular compromise.¹² People with VWD are particularly vulnerable to physical trauma and may experience life-threatening bleeding following accidents or injuries. As a result, contact sports, falling or banging your head may all be life-altering. In events where there is severe bleeding, or if you require additional medical support, you may even need to be cared for in a critical care environment.¹³

The complications and side effects of VWD treatment may be minor, such as feeling sick or getting headaches, but may also include more serious adverse effects, such as allergic reactions, dangerously low sodium levels, or blood clots. Therefore, it is important to speak to your healthcare team about any specific adverse effects that may be linked to your treatment so they can advise on how to minimise these as well as when to seek additional advice. 

Summary

Von Willebrand Disease is a well-understood bleeding disorder, but it can be tricky to confidently diagnose, as both its course and symptoms can vary significantly between individuals. Medical professionals are equipped with a number of strategies for treating bleeding events and the associated consequences. Despite this, you must remain extra vigilant in reporting any excessive bleeding as well as seeking urgent care in the event of physical trauma or bleeding that does not stop.