Overview of Von Willebrand Disease

Hey everyone, in this lesson we're going to talk about von Willebrand disease. Von Willebrand disease is important because it is the most common inherited bleeding disorder and von Willebrand disease is due to an issue with von Willebrand factor. We're going to talk about more about that later on in the lesson. It's so common that it affects about one percent of the population and men and women are equally affected. It is inherited through autosomal dominant and autosomal recessive depending on the time. type of von Willebrand disease, and we're also going to talk a little more about the types of von Willebrand disease later on. The von Willebrand factor gene, or VWF gene, is the culprit, and this is located on chromosome 12. So von Willebrand factor, or VWF, has particular functions in hemostasis. One important function of von Willebrand factor is that it is important in platelet aggregation and adhesion. So how does it do this? Well, with platelets, platelets have a receptor known as glycoprotein 2b3a or GP2b3a. Von Wilbern factor binds to this receptor. Von Wilbern factor is itself a glycoprotein. It can bind to glycoprotein 2b3a not only on only one platelet, but it can bind to that same receptor on multiple platelets. leading to these platelets being able to essentially stick together. This leads to platelet aggregation and adhesion. Von Willebrand factor also acts as a chaperone for factor VIII. It can also regulate angiogenesis, and it's also important in bone metabolism. So the Von Willebrand factor VIII complex has been shown to inhibit rank L-induced osteoclastogenesis. So it has multiple functions. Von Willebrand factor is located, or it forms, what we call Weeble-Pallade bodies. So these are essentially vesicles filled with von Willebrand factor. They're located in the endothelium, and then they can essentially release von Willebrand factor into circulation. Von Willebrand factor is also interesting because it exists as a set of multimers of different sizes. And essentially, the largest of the multimers are responsible for platelet aggregation adhesion. So if we have a larger von Willebrand factor, they're able to bind to even more platelets to form larger platelet aggregates. So that's why the largest of... the von Willebrand factor multimers are important and responsible for platelet adhesion and aggregation. So when it comes to von Willebrand's disease, what are some of the clinical features? There is a history of bleeding. Now, von Willebrand's disease bleeding is not as severe as other bleeding disorders. Generally, we see mucocutaneous bleeds. These include bleeds of the gingiva, so bleeds around individuals' teeth, so bloody gums. They can also have epistaxis, so bloody nose. They can also have menorrhagia. This can be one of the most common findings with von Willebrand disease patients. Generally with women with von Willebrand disease, they might not know they have the disease, but they have a history of menorrhagia. individuals and their family have menorrhagia, this can be a clue to figuring out if these individuals have von Willebrand's disease or not. Some other features include easy bruising, GI bleeds, post-operative bleeding, and immediate bleeding after trauma. This distinguishes itself from other types of bleeding disorders, which generally have bleeds a little bit after a trauma. Now, most of it is mucocutaneous bleeding, but with a certain type of von Willebrand disease, type 3, we actually see musculoskeletal bleeding. This is the more severe case of von Willebrand disease. So how do we classify it? We classify it into three types. Type 1 is what we call mild quantitative defect. It generally means that there's a decreased amount in activity of non-mullibrand factor. Majority of cases fall within type 1 and generally around 80% of cases. And this is when we call this an autosomal dominant inheritance. Type 1 is autosomal dominant inheritance. We generally see this run through families. Again, coming back to that same example with menorrhagia, we see women... throughout the family having menorrhagia, it may be type 1 von Willebrand disease. Type 2 has several subtypes. Type 2 is generally what we call qualitative or a functional defect. So we have von Willebrand factor, but it is not as active. It has a decreased activity or decreased function. Type 2a, so there are four subsets or four subcategories of type 2. 2A is impaired multimerization. We have the Von Willebrand factor, but it doesn't multimerize as well as it should, and that would lead to an impairment in platelet aggregation and adhesion, since larger multimers are more responsible for the platelet adhesion and aggregation. Type 2B is what we call hyperfunctional platelet binding. It essentially will bind too much to platelets. 2M has decreased glycoprotein 1B binding, and 2N has decreased factor VIII binding. So all of these have important consequences. The last type, type 3, is what we call a severe total quantitative defect. Essentially, no von Willebrand factor is produced in this type. And this is the rarest or the most uncommon of the types of von Willebrand disease. It is an autosomal recessive inheritance. And with regards to type 2, depending on the subcategory of type 2, it can either be autosomal dominant or autosomal recessive inheritance. Now when we look at an agarose gel, looking at the different multimers of von Willebrand factor, we can see how these types look. Type 2a, seen here, we see that there is impaired multimerization. The largest multimers are missing, so we only have the smallest ones. With type 3a, we see that there is impaired multimers. The largest multimers are missing, Type 2b, we have hyperfunctional platelet binding. So it's normal, but it binds to platelets inappropriately. Type 1, we see, is a mild quantitative defect. It's decreased amount. There's an actual, you can see a lightening of the bands here. And type 3, there's actually nothing. There's no von Willebrand factor formed. So in this agros, you can actually see the different types. here. Now, before I move on, I want to talk about an acquired von Willebrand disease. Acquired von Willebrand disease is associated with particular conditions. One of them is aortic stenosis. Aortic stenosis due to the aortic valve and the stenosis and the decreased amount of area by which blood can go through. that stenotic valve, it can lead to an acquired von Willebrand disease, and it can lead to something known as Hayes syndrome. This is similar to mechanical heart valves, and mechanical heart valves can lead to an acquired von Willebrand disease, and both of these are really due to a stenotic valve or something that causes shear stress. The shear stress can basically tear or unravel the von Willebrand's factor, making it less functional. And another condition that causes an acquired von Willebrand's disease is Wilm's tumor. Generally, all of these acquired von Willebrand's disease are due to a depletion of von Willebrand factor simply because of, a lot of times, sheer stress leading to a unraveling and destruction of von Willebrand factor. If we're suspicious of von Willebrand's disease, how do we investigate it? What can we do to... figure out if it is von Willebrand's disease. Some of these include some of the basics. We want to do a CBC to look at platelet count. We want to do an INR and a PTT. We also want to do von Willebrand's factor activity and von Willebrand factor antigen. So we want to look at how much von Willebrand factor there is and how much activity that von Willebrand factor has. We also want to look at factor. eight, and these can all help us to determine what if the patient has von Willebrand's disease, and it can help us determine what type it is. We can also look into genetic testing as well. Now, blood type, before I move on, blood type is important to keep in mind because the blood type of an individual can affect the presentation pathology of von Willebrand's disease. Interestingly, type O blood types have generally lower levels of von Willebrand's factor. This doesn't mean that they have von Willebrand's disease, but on average, people with type O blood have slightly lower levels of von Willebrand's factor than other blood types. And on the opposite side, type AB have higher levels of von Willebrand's factor than other blood types. So when we want to make the diagnosis, of von Willebrand's disease, we have to think about the patient's blood type. We have to keep that in mind. So how do we make the diagnosis? Again, it all comes down to the level of activity and the level of von Willebrand's factor. Decreased level of activity in antigen, we call that type 1. So we still have von Willebrand's factor, but it's in a decreased amount. And again, we got to keep that in context with the person's blood type. If we find that the activity is low, generally lower than 0.6 of the antigen level, so activity is lower than the amount of von Willebrand's factor, this is a functional problem. This is either type 2a or type 2b von Willebrand's disease. If we see that factor 8 is a lot less than von Willebrand's factor, this is considered type 2n. And if we see no von Wilberman factor at all, this is type 3. Once you've made the diagnosis, treatment generally involves a couple of things. One is desmopressin or DDAVP. DDAVP is a synthetic vasopressin analog, and it's used to treat type 1 and 2A von Wilberman's disease. It's generally not... as helpful for other types. Desmopressin itself induces the release of von Willebrand's factor and factor VIII from endothelial cells. So whatever we have, whatever von Willebrand factor we have, and whatever factor VIII we have, desmopressin induces the release of these factors from endothelial cells. Now, in other cases, in other severe cases, we might need to use factor VIII transfusion. We might also need to, depending on the clinical picture, we might need to do blood transfusions if there's severe bleeds to correct for anemias, those types of things. But generally, these are the two types of treatments. We use desmopressin for some of the less severe cases, type 1 and 2A, Fondle-Lobarin's disease, and sometimes we'll use a factor VIII transfusion if factor VIII is low. So anyways, guys, I hope you found this lesson. helpful. This was a lesson on von Willebrand's disease. If you found this lesson helpful, please like and subscribe for more videos like this one. And as always, thank you so much for watching, and I'll see you next time.

It's so common that it affects about one percent of the population and men and women are equally affected. It is inherited through autosomal dominant and autosomal recessive depending on the time. type of von Willebrand disease, and we're also going to talk a little more about the types of von Willebrand disease later on. The von Willebrand factor gene, or VWF gene, is the culprit, and this is located on chromosome 12. So von Willebrand factor, or VWF, has particular functions in hemostasis. One important function of von Willebrand factor is that it is important in platelet aggregation and adhesion.

So how does it do this? Well, with platelets, platelets have a receptor known as glycoprotein 2b3a or GP2b3a. Von Wilbern factor binds to this receptor. Von Wilbern factor is itself a glycoprotein.

It can bind to glycoprotein 2b3a not only on only one platelet, but it can bind to that same receptor on multiple platelets. leading to these platelets being able to essentially stick together. This leads to platelet aggregation and adhesion.

Von Willebrand factor also acts as a chaperone for factor VIII. It can also regulate angiogenesis, and it's also important in bone metabolism. So the Von Willebrand factor VIII complex has been shown to inhibit rank L-induced osteoclastogenesis.

So it has multiple functions. Von Willebrand factor is located, or it forms, what we call Weeble-Pallade bodies. So these are essentially vesicles filled with von Willebrand factor. They're located in the endothelium, and then they can essentially release von Willebrand factor into circulation.

Von Willebrand factor is also interesting because it exists as a set of multimers of different sizes. And essentially, the largest of the multimers are responsible for platelet aggregation adhesion. So if we have a larger von Willebrand factor, they're able to bind to even more platelets to form larger platelet aggregates.

So that's why the largest of... the von Willebrand factor multimers are important and responsible for platelet adhesion and aggregation. So when it comes to von Willebrand's disease, what are some of the clinical features? There is a history of bleeding.

Now, von Willebrand's disease bleeding is not as severe as other bleeding disorders. Generally, we see mucocutaneous bleeds. These include bleeds of the gingiva, so bleeds around individuals' teeth, so bloody gums. They can also have epistaxis, so bloody nose.

They can also have menorrhagia. This can be one of the most common findings with von Willebrand disease patients. Generally with women with von Willebrand disease, they might not know they have the disease, but they have a history of menorrhagia.

individuals and their family have menorrhagia, this can be a clue to figuring out if these individuals have von Willebrand's disease or not. Some other features include easy bruising, GI bleeds, post-operative bleeding, and immediate bleeding after trauma. This distinguishes itself from other types of bleeding disorders, which generally have bleeds a little bit after a trauma.

Now, most of it is mucocutaneous bleeding, but with a certain type of von Willebrand disease, type 3, we actually see musculoskeletal bleeding. This is the more severe case of von Willebrand disease. So how do we classify it?

We classify it into three types. Type 1 is what we call mild quantitative defect. It generally means that there's a decreased amount in activity of non-mullibrand factor. Majority of cases fall within type 1 and generally around 80% of cases. And this is when we call this an autosomal dominant inheritance.

Type 1 is autosomal dominant inheritance. We generally see this run through families. Again, coming back to that same example with menorrhagia, we see women... throughout the family having menorrhagia, it may be type 1 von Willebrand disease.

Type 2 has several subtypes. Type 2 is generally what we call qualitative or a functional defect. So we have von Willebrand factor, but it is not as active. It has a decreased activity or decreased function.

Type 2a, so there are four subsets or four subcategories of type 2. 2A is impaired multimerization. We have the Von Willebrand factor, but it doesn't multimerize as well as it should, and that would lead to an impairment in platelet aggregation and adhesion, since larger multimers are more responsible for the platelet adhesion and aggregation. Type 2B is what we call hyperfunctional platelet binding. It essentially will bind too much to platelets. 2M has decreased glycoprotein 1B binding, and 2N has decreased factor VIII binding.

So all of these have important consequences. The last type, type 3, is what we call a severe total quantitative defect. Essentially, no von Willebrand factor is produced in this type. And this is the rarest or the most uncommon of the types of von Willebrand disease. It is an autosomal recessive inheritance.

And with regards to type 2, depending on the subcategory of type 2, it can either be autosomal dominant or autosomal recessive inheritance. Now when we look at an agarose gel, looking at the different multimers of von Willebrand factor, we can see how these types look. Type 2a, seen here, we see that there is impaired multimerization.

The largest multimers are missing, so we only have the smallest ones. With type 3a, we see that there is impaired multimers. The largest multimers are missing, Type 2b, we have hyperfunctional platelet binding. So it's normal, but it binds to platelets inappropriately. Type 1, we see, is a mild quantitative defect.

It's decreased amount. There's an actual, you can see a lightening of the bands here. And type 3, there's actually nothing.

There's no von Willebrand factor formed. So in this agros, you can actually see the different types. here.

Now, before I move on, I want to talk about an acquired von Willebrand disease. Acquired von Willebrand disease is associated with particular conditions. One of them is aortic stenosis.

Aortic stenosis due to the aortic valve and the stenosis and the decreased amount of area by which blood can go through. that stenotic valve, it can lead to an acquired von Willebrand disease, and it can lead to something known as Hayes syndrome. This is similar to mechanical heart valves, and mechanical heart valves can lead to an acquired von Willebrand disease, and both of these are really due to a stenotic valve or something that causes shear stress.

The shear stress can basically tear or unravel the von Willebrand's factor, making it less functional. And another condition that causes an acquired von Willebrand's disease is Wilm's tumor. Generally, all of these acquired von Willebrand's disease are due to a depletion of von Willebrand factor simply because of, a lot of times, sheer stress leading to a unraveling and destruction of von Willebrand factor.

If we're suspicious of von Willebrand's disease, how do we investigate it? What can we do to... figure out if it is von Willebrand's disease.

Some of these include some of the basics. We want to do a CBC to look at platelet count. We want to do an INR and a PTT.

We also want to do von Willebrand's factor activity and von Willebrand factor antigen. So we want to look at how much von Willebrand factor there is and how much activity that von Willebrand factor has. We also want to look at factor.

eight, and these can all help us to determine what if the patient has von Willebrand's disease, and it can help us determine what type it is. We can also look into genetic testing as well. Now, blood type, before I move on, blood type is important to keep in mind because the blood type of an individual can affect the presentation pathology of von Willebrand's disease.

Interestingly, type O blood types have generally lower levels of von Willebrand's factor. This doesn't mean that they have von Willebrand's disease, but on average, people with type O blood have slightly lower levels of von Willebrand's factor than other blood types. And on the opposite side, type AB have higher levels of von Willebrand's factor than other blood types. So when we want to make the diagnosis, of von Willebrand's disease, we have to think about the patient's blood type. We have to keep that in mind.

So how do we make the diagnosis? Again, it all comes down to the level of activity and the level of von Willebrand's factor. Decreased level of activity in antigen, we call that type 1. So we still have von Willebrand's factor, but it's in a decreased amount.

And again, we got to keep that in context with the person's blood type. If we find that the activity is low, generally lower than 0.6 of the antigen level, so activity is lower than the amount of von Willebrand's factor, this is a functional problem. This is either type 2a or type 2b von Willebrand's disease.

If we see that factor 8 is a lot less than von Willebrand's factor, this is considered type 2n. And if we see no von Wilberman factor at all, this is type 3. Once you've made the diagnosis, treatment generally involves a couple of things. One is desmopressin or DDAVP.

DDAVP is a synthetic vasopressin analog, and it's used to treat type 1 and 2A von Wilberman's disease. It's generally not... as helpful for other types. Desmopressin itself induces the release of von Willebrand's factor and factor VIII from endothelial cells. So whatever we have, whatever von Willebrand factor we have, and whatever factor VIII we have, desmopressin induces the release of these factors from endothelial cells.

Now, in other cases, in other severe cases, we might need to use factor VIII transfusion. We might also need to, depending on the clinical picture, we might need to do blood transfusions if there's severe bleeds to correct for anemias, those types of things. But generally, these are the two types of treatments. We use desmopressin for some of the less severe cases, type 1 and 2A, Fondle-Lobarin's disease, and sometimes we'll use a factor VIII transfusion if factor VIII is low.

So anyways, guys, I hope you found this lesson. helpful. This was a lesson on von Willebrand's disease.

If you found this lesson helpful, please like and subscribe for more videos like this one. And as always, thank you so much for watching, and I'll see you next time.

Transcript for:Overview of Von Willebrand Disease

Transcript for:
Overview of Von Willebrand Disease