Inherited Bleeding Disorders and Genetic Factors: Insights

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Often bleeding disorders are inherited, meaning the disorder is passed from parents to their children. Although some people may have acquired bleeding disorders or have a spontaneous genetic mutation, many people have inherited bleeding disorders. Inheritance and genetics can seem complex, but it is important to understand how a person can get a bleeding disorder.

The genetics of bleeding disorders involve chromosomes, which are the structures where genes are located. Genes are the instructions that tell your body how to make the proteins needed for blood clotting. If there is a problem with a specific gene that affects a protein needed for blood clotting, then a person may have a bleeding disorder.

This section about how does a person get a bleeding disorder covers the following:

How Does a Person Get Hemophilia?

How Does a Person Get von Willebrand Disease?

How Does a Person Get a Rare Factor Deficiency?

How Does a Person Get a Rare Platelet Disorder?

How Does a Person Get Hemophilia?

Hemophilia affects people from all racial and ethnic groups. It is caused by a problem in one of your genes. Genes tell the body to make the clotting factor proteins needed to form a blood clot. The gene for hemophilia is carried on the X chromosome. Males assigned at birth have one X and one Y chromosome (XY). Females assigned at birth have two X chromosomes (XX).
Because males assigned at birth only have one X chromosome, if they receive an X chromosome that has the affected gene, then they have hemophilia. Females assigned at birth have two X chromosomes and experience varying degrees of bleeding symptoms. If bleeding symptoms are present, then females assigned at birth may have hemophilia. If no bleeding symptoms are present, then females assigned at birth are said to be "carriers" of hemophilia. They carry the gene that causes hemophilia on the X chromosome and could pass the affected gene onto their children. 
If only one X chromosome is affected, bleeding symptoms may or may not be present.
Although hemophilia is a genetic disorder, random genetic mutations sometimes occur in people who don’t have a genetic link to the condition. About one-third of people who are diagnosed with hemophilia have no family history of it.
There are two types of hemophilia including hemophilia A and B. Hemophilia A is about four times more common than hemophilia B. Half of those with hemophilia A have a severe form, which means they have less than 1% of the clotting factor they need.

Below are two diagrams of an X-linked recessive inheritance pattern:

How do you get Hemophilia

X-Linked Pattern 2

If you want more information about hemophilia, please go to Hemophilia.

How Does a Person Get von Willebrand Disease?

VWD is a genetic disorder that is inherited, or passed down, from parent to child. VWD is an autosomal chromosome disorder, not an X-linked chromosome disorder like hemophilia. VWD affects men and women equally, so a child can inherit VWD from either of their biological parents or both parents. If you have VWD, there is a 50% chance you will pass the gene down to your child. VWD affects people from all racial and ethnic groups.
In some cases, VWD can occur when only one parent passes down the affected gene to a child. In other cases, a child will inherit the disorder only when both parents have the gene. Even if both parents have mild symptoms or no symptoms at all, their children can still be severely affected.
There are several different types and subtypes of VWD. To get VWD types 1 and 2 (except 2N), only one parent has to have the gene and pass it down to their child. This is a dominant inheritance pattern. For type 3 and type 2N, in order to have the disorder both parents have the affected gene and pass it down to their child. This is a recessive inheritance pattern.1
Although rarer, VWD can also be acquired, meaning it is not inherited. Acquired VWD is often related to an underlying disorder like a cardiovascular disorder.

If you want more information about von Willebrand disease, please go to Von Willebrand Disease.

How Does a Person Get a Rare Factor Deficiency?

Deficiencies in the other clotting factors are not X-linked and instead the affected gene is passed down in an autosomal recessive pattern or in some cases an autosomal dominant pattern. In an autosomal recessive pattern, a child would have to receive the affected gene from both parents to have the disorder. If the child receives the affected gene from only one parent, they will be a carrier of the deficiency and may have mild symptoms. These rare clotting factor deficiencies occur equally for men and women.

Below is a diagram of autosomal recessive inheritance pattern:

family inheritance

Below is a diagram of autosomal dominant inheritance pattern:

Autosomal Dominant Inheritance

Factor I (1) Deficiency

Factor I (1) deficiency is a collective term for three rare inherited fibrinogen deficiencies. These deficiencies include afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia. Afibrinogenemia is inherited in an autosomal recessive pattern which means both parents must carry the gene to pass it onto their child. Dysfibrinogenemia is inherited in an autosomal dominant pattern, which means that only one parent must carry the gene to pass it on to a child. Hypofibrinogenemia can be inherited in either autosomal dominant or autosomal recessive patterns. Factor I (1) deficiency affects men and women equally.

Factor II (2) Deficiency

Factor II (2) deficiency is inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor II (2) deficiency affects men and women equally.

Factor V (5) Deficiency

Factor V (5) deficiency is usually inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor V (5) deficiency affects men and women equally.

Factor VII (7) Deficiency (Alexander’s Disease)

Factor VII (7) is inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor VII (7) deficiency affects men and women equally.

If you want more information about factor VII (7) deficiency, please go to the Factor VII (7) Booklet.

Factor X (10) Deficiency (Stuart-Prower Factor)

 Factor X (10) is inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor X (10) deficiency affects men and women equally.

If you want more information about factor X (10) deficiency, please go to the Factor X (10) Booklet.

Factor XI (11) Deficiency (Hemophilia C)

Factor XI (11) deficiency is inherited in an autosomal recessive pattern. Both parents must carry the affected gene to pass the disorder on to their children. In some cases, factor XI (11) deficiency can also be inherited in an autosomal dominant pattern.3 This means children with only one affected parent may inherit the condition. Men and women are affected by factor XI (11) deficiency equally.

Factor XII Deficiency (Hageman Factor)

Factor XII (12) deficiency is inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor XII (12) deficiency affects men and women equally. It is more common in Asian people or Pacific Islander people.

Factor XIII Deficiency

Factor XIII (13) deficiency is inherited in an autosomal recessive pattern. Both parents must carry the gene to pass the disorder on to their children. Factor XIII (13) deficiency affects men and women equally.

If you want more information about factor XIII (13) deficiency, please go to the Factor XIII (13) Booklet.

How Does a Person Get a Rare Platelet Disorder?

Rare platelet disorders can be inherited in different ways, depending on the disorder. Some disorders are inherited through an autosomal recessive pattern while others may be inherited through an autosomal dominant or X-linked pattern.

Bernard-Soulier Syndrome (BSS)

BSS is inherited in an autosomal recessive pattern.2 Both parents must carry the abnormal gene to pass the disorder on to their children. BSS affects men and women equally.

Glanzmann’s Thrombasthenia (GT)

GT is inherited in an autosomal recessive pattern. Both parents must carry the abnormal gene to pass the disorder on to their children. GT affects men and women equally.

If you want more information about Glanzmann’s Thrombasthenia, please go to the Glanzmann’s Thrombasthenia Booklet.

Platelet Storage Pool Deficiency (PSPD)

Forms of PSPD may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. See the chart below for more detail on how the different forms of PSPD are inherited. If you want more information about Platelet Storage Pool Deficiency, please go to the Platelet Storage Pool Deficiency Booklet.

pspd

References

1. CDC. (2021, June 29). How von Willebrand disease is inherited. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/inherited.html

2. NORD. (2018, June 26). Bernard-Soulier syndrome. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/bernard-soulier-syndrome/#:~:text=Bernard%2DSoulier%20syndrome%20is%20usually,abnormal%20gene%20from%20each%20parent.

3. NORD. (2022, April 27). Factor XI deficiency. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/factor-xi-deficiency/#:~:text=Factor%20XI%20deficiency%20is%20usually,working%20gene%20from%20each%20parent

Bleeding disorders are most often inherited, which means the disorder is passed from biological parents to their children. A smaller number of people may get a disorder without a family history of it. This is called a spontaneous genetic mutation. It may seem complicated to understand how you get a bleeding disorder. But it is important to understand how this can happen.

Basics of Getting a Bleeding Disorder

You are made up of many cells. Each cell has chromosomes, genes and DNA. You have 23 pairs of chromosomes for a total of 46 chromosomes. Half of the chromosomes (23) come from one biological parent; the other half (23) comes from the other biological parent. Two of these 46 chromosomes are called sex chromosomes. Most people, who are assigned female at birth have 2 ‘X’ chromosomes. Most people assigned male at birth have 1 ‘X’ chromosome and 1 ‘Y’ chromosome.

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How do you get Hemophilia?

Hemophilia is caused by a mutation in one of your genes. This gene tells your body to make the clotting factor proteins needed to form a blood clot. The gene for hemophilia is carried on one of the sex chromosomes, the X chromosome.

Males assigned at birth most commonly only have 1 X chromosome. If they receive an X chromosome that has the affected gene, then they have hemophilia.

Females assigned at birth have two X chromosomes. They can have varying degrees of bleeding symptoms if the hemophilia gene is passed on to them. If bleeding symptoms are present, then females assigned at birth have hemophilia. If no bleeding symptoms are present, then females assigned at birth are said to be "carriers" of hemophilia. They carry the gene that causes hemophilia and could pass the affected gene onto their children.  

Although many people get hemophilia from their parents, not everyone does. About one-third of people who are diagnosed with hemophilia have no family history of it. 

Below are two diagrams of how you can get hemophilia. This is called an X-linked recessive inheritance pattern:  

How do you get Hemophilia

X-Linked Pattern 2

If you want more information about hemophilia, please go to Hemophilia. 

How do you get von Willebrand Disease?

VWD is caused by a problem in one of your genes that tells your body to make von Willebrand factor (VWF). VWF helps your blood clot well. Unlike hemophilia, which is an X-linked chromosome disorder, VWD is an autosomal chromosome disorder. This means the affected gene is not found on one of the sex chromosomes like hemophilia. Instead, it is on one of the other chromosomes.

In some cases, VWD can happen when only one parent passes down the affected gene to a child. In other cases, a child will get the disorder only when both parents have the gene. Even if both of your parents have mild symptoms or no symptoms at all, you can still be severely affected.  

There are several different types and subtypes of VWD.

To get types 1 and 2 (except 2N), only one biological parent has to have the gene. The biological parent then passes it down to their child. This is called a dominant inheritance pattern.
To get type 3 and type 2N, both parents have the affected gene and pass it down to their child. This is called a recessive inheritance pattern.1

Although rarer, VWD can also be acquired.

If you want more information about von Willebrand disease, please go to Von Willebrand Disease. 

How do you get a Rare Factor Deficiency?

Just like VWD and hemophilia, other rare factor deficiencies are caused by a mutation of a gene. Like VWD, deficiencies in other clotting factors are not found on the sex chromosomes. Instead, they are found on one of the other chromosomes. These are autosomal chromosome disorders. They are passed down in an autosomal recessive or dominant pattern, depending on the specific disorder.

In an autosomal recessive pattern, you need two genes to have the disorder. However, in an autosomal dominant pattern you will only need one gene. get the affected gene from both parents to have the disorder.

In an autosomal dominant pattern, you get the affected gene from one parent who has the disorder. For rare factor deficiencies with an autosomal recessive pattern, you will be a carrier of the deficiency and may have mild bleeding symptoms.

Below is a diagram of autosomal recessive inheritance pattern: 

family inheritance

Rare factor deficiencies that follow an autosomal recessive inheritance pattern include: Afibrinogenemia (FI (1) deficiency), Factor II (2) deficiency, Factor V (5) deficiency, Factor VII (7) deficiency, Factor X (10) deficiency, Factor XI (11) deficiency, Factor XII (12) deficiency, and Factor XIII (13) deficiency.

autosomal

Below is a diagram of autosomal dominant inheritance pattern:   

Rare factor deficiencies that follow an autosomal dominant inheritance pattern include: Dysfibrinogenemia (FI (1) deficiency) and Hypofibrinogenemia (FI (1) deficiency).

How do you get a Rare Platelet Disorder?

Unlike hemophilia or VWD, rare platelet disorders can be passed on in different ways depending on which one it is. Some rare platelet disorders are passed down through an X-linked pattern. Some are passed down through an autosomal recessive pattern. Others are passed down through autosomal dominant pattern.

Bernard-Soulier Syndrome (BSS)

BSS is passed down in an autosomal recessive pattern.2 Both parents must carry the affected gene to pass the disorder on to their children. BSS affects men and women equally.  

Glanzmann’s Thrombasthenia (GT)

GT is passed down in an autosomal recessive pattern. Both parents must carry the affected gene to pass the disorder on to their children. GT affects men and women equally.  

  If you want more information about Glanzmann’s Thrombasthenia, please go to the Glanzmann’s Thrombasthenia Booklet. 

Platelet Storage Pool Deficiency (PSPD)

Forms of PSPD may be passed down in an autosomal dominant, autosomal recessive, or X-linked pattern. See the chart below for more detail on how you can get different forms of PSPD.

If you want more information about Platelet Storage Pool Deficiency (PSPD), please go to the Platelet Storage Pool Deficiency (PSPD) booklet.

pspd

References

1. CDC. (2021, June 29). How von Willebrand disease is inherited. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/inherited.html

2. NORD. (2018, June 26). Bernard-Soulier syndrome. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/bernard-soulier-syndrome/#:~:text=Bernard%2DSoulier%20syndrome%20is%20usually,abnormal%20gene%20from%20each%20parent.

3. NORD. (2022, April 27). Factor XI deficiency. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/factor-xi-deficiency/#:~:text=Factor%20XI%20deficiency%20is%20usually,working%20gene%20from%20each%20parent