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Genetic Clotting Disorders

Some children are born with a disorder also known as a genetic condition that makes them at greater risk for a blood clot, a blockage in a child's veins or arteries. A genetic condition is something that is passed down from a child's parent(s). These conditions include:


Factor V(5) Leiden

Factor V(5) Leiden is the most common genetic condition that can lead to blood clots. Almost all people with factor V Leiden have one affected gene and one normal gene. A gene is a characteristic that is passed down from a child’s parent(s). It is rare for a child to have both genes affected.
 
Factor V is a protein that helps form blood clots, a plug that help stop bleeding. With factor V Leiden a child’s body cannot turn off factor V. As a result too much blood clotting can happen.

For children with one affected gene the chance of getting a blood clot increases 10 times. This means that for children with factor V Leiden, 1 out of 5,000-10,000 will get a blood clot. Children who are healthy and do not have factor V Leiden will get a blood clot in 1 out of 50,000-100,000 children. In the rare case that both genes are affected, their chance of getting a blood clot is 100-fold higher than someone without factor V Leiden. This means that 1 out of 500-1,000 children with two affected genes will get a blood clot.

Most children with factor V Leiden will never get a blood clot in their childhood or young adult life. A child’s risk of getting a clot increases when they have a serious medical condition, a central line, an undiagnosed autoimmune disease or is on birth control (also known as oral conraceptives and hormones).

For example: In otherwise healthy teenagers only 1 out of 50,000 will get a blood clot. For someone who is on birth control, she has about a 3-fold risk of getting a blood clot. If the child also has factor V Leiden, then the risk for getting a blood clot is 30-40 times higher than an otherwise healthy teenager.

In other words, if a 16 year old girl who has factor V Leiden is put on the birth control pill, her risk of getting a blood clot is 35 out of 50,000 or about 1 out of 1,500. 

Who it affects:

Factor V Leiden affects different groups of people.

  • Families with ancestry in the Middle East (Arab countries, Turkey and Armenia) have the highest rates of around 10%.
  • Families with ancestry in Southern Europe (Greece and Italy) have rates of around 5%.
  • Families with ancestry in Central and Northern Europe have rates around 2-5%.
  • The one gene mutation for factor V Leiden occurs in about 2-10% of Caucasians.
  • People who have no white ancestors (African, Asian, Native American or Pacific Islanders) do not have factor V Leiden in their genes.
    • In the United States, many people have a mixed ancestry which they may or may not be aware of. As a result, many people whose family has been in the United States for many generations may have factor V Leiden regardless of their race or ethnic group. .


The Prothrombin Mutation

The prothrombin mutation is the second most common genetic clotting disorder. Almost all children with the prothrombin mutation have one gene (a characteristic passed down from a child’s parent(s) that is affected. It is uncommon for a child to have both genes affected by the mutation.

Prothrombin is an important part of normal blood clotting, forming a plug to stop bleeding. Children with the prothrombin mutation have too much prothrombin in their blood which causes the body to produce more blood clots.

Children with one gene affected have a 2-3 fold increased risk of getting a blood clot. This means that 2-3 out of 1,000 children with the condition will get a blood clot. Children who are healthy and do not have the prothrombin mutation will get a blood clot in 1 out of 50,000-100,000 children.  For children that have both genes affected, they have a greater chance of getting a blood clot than a child that only has one affected gene.

Most children with the prothrombin mutation will never get a blood clot in their childhood or young adult life. A person’s risk of getting a clot increases when she or he has a serious medical condition, a central line, an undiagnosed autoimmune disease and/or is on birth control (also known as oral contraceptives or hormones).

Who it affects:

The prothrombin mutation affecting one gene occurs in about 2-3% of children with white ancestry. Children with a mixed ancestry can be affected as well.

About 1 out of 10,000 children will have the prothrombin mutation affecting both genes.


Protein C and Protein S Deficiency

Protein C and protein S work together in the body to prevent blood clots. If a child does not have enough of either protein, they are at risk for getting a blood clot.

A child’s risk for getting a blood clot increases by 10-20 fold if they inherit (passed down from a child’s parents) protein C or protein S deficiency. Most children with either condition will not get a blood clot during their childhood and teen years.

Protein C Deficiency

  • Affects all races
  • Inherited protein C deficiency occurs in 1 out of 1,000 people
  • Treatment: patients are treated with Ceprotin, a blood-derived product that replaces the missing protein C

Protein S Deficiency

  • Affects all races
  • Inherited protein S deficiency occurs in 1 out of 5,000 people
  • Treatment: patients are treated with plasma or blood thinners

Severe Protein C and Protein S Deficiency

Severe protein C or protein S deficiency is a rare (less than 1 out of a million people), but severe condition. Babies with severe protein C or protein S deficiency are born with blood clots that often cause brain damage and blindness. Doctors will be alerted to the condition after birth because babies will have large purple patches on their skin. These patches are blood clots within the skin.

Non-Genetic Protein C and Protein S Deficiency

Children with liver disease or vitamin K deficiency can also become deficient in protein C or protein S. It is unlikely for the average child or adolescent to have undiagnosed liver disease or vitamin K deficiency.


Antithrombin Deficiency

Antithrombin is a natural protein in the human body whose job is to prevent blood clots. Not having enough antithrombin in the body can lead to blood clots. Antithrombin deficiency has an even higher rate of causing blood clots than protein C or protein S deficiency and often causes blood clots in childhood or the teen years.

Who it affects:

Antithrombin deficiency occurs in about 1 out of 20,000-50,000 people. The chance of a person getting a blood clot depends on how much antithrombin is in their body.

Treatment:
Once a child is diagnosed with antithrombin deficiency due to having a blood clot they can be treated with:

  • Blood thinners – which are usually enough to treat and prevent blood clots
  • Antithrombin-containing factors – either blood-derived or synthetic (man-made)


Elevated Homocysteine

Homocysteine is an amino acid (a building block for protein) and is found naturally in the human body. Certain genetic conditions, a disorder passed down from a child’s parents, can lead to high homocysteine in the blood. High homocysteine can cause blood clots or a blockage in arteries and veins. There are rare conditions of high homocysteine levels (more than 100 with normal being less than 12), but these conditions are associated with many other medical problems and are diagnosed shortly after birth or in the first year of life.

More commonly, high homocysteine can be caused by a poor diet lacking B vitamins (B6, B12 and folic acid) or by diseases of the blood or intestine that causes the body to not absorb these vitamins. Children with poor kidney function may also see abnormally high homocysteine levels.

Treatment:

  • Lower the homocysteine levels using vitamins B6, B12 and/or folic acid
  • For children with blood clots from high homocysteine levels, see a doctor to discuss the use of blood thinners to prevent blood clots


Elevated Lipoprotein(a)

Lipoprotein(a) is a naturally occurring lipoprotein. It is similar to the lipoproteins known as cholesterol. The function of lipoprotein(a) in the body is not known.

In some families, lipoprotein(a) can be high just like cholesterol. High lipoprotein(a) can lead to blood clots.

Unfortunately, there is no good way to lower lipoprotein(a). Unlike cholesterol, lipoprotein(a) is not affected by diet or exercise. High doses of the vitamin niacin can lower lipoprotein(a) in some cases, but niacin has side effects and does not always work.

Children who have had a blood clot because of high lipoprotein(a) need to be treated with blood thinners and may need to stay on them for a long time.


Elevated Factor VIII (8)

High factor VIII (8) levels can lead to blood clots and there are families that genetically have high factor VIII. Factor VIII is a protein that helps stop bleeding in a child’s body.

Factor VIII can also be elevated due to infection, inflammation and autoimmune diseases. It is not clear at what level of factor VIII someone is at risk for a blood clot. Some doctors who are testing for thrombophilia will not test for a high factor VIII level.


Antiphospholipid Antibody Syndrome (APLA or APLAS)

Unlike most other thrombophilias, antiphospholipid antibody syndrome (APLAS) is an acquired disorder, meaning one does not have the condition from birth. APLAS is an autoimmune disease, causing the immune system to work too much and attack healthy parts of a child’s body.  Like autoimmune diseases, APLAS runs in families, but there is not a specific gene for APLAS like factor V Leiden.

The cause of this condition and how often it affects children is not known, but it is not rare. It is not completely clear how APLAS leads to blood clots. Hematologists think that APLAS causes holes to be made on the surface of cells that line blood vessels and normally prevent blood clots from forming in the vessel.

The condition is more common in adolescent girls and young women than in boys or men. It can cause many problems in pregnancy for women who have the condition.

It is important to test for APLAS in otherwise healthy children who get a blood clot. Special blood tests are needed to test for APLAS and the results can be tricky to understand. As a result, an expert in blood clotting conditions needs to explain the blood test results.

Patients with APLAS who get blood clots need to be treated with blood thinners and should be managed by a doctor who specializes in blood clotting disorders. Contact the Hemostasis & Thrombosis Center to speak with one of our experts.