Hereditary (or inherited) thrombocytopenia refers to a group of conditions where changes in certain genes cause low platelet counts. There is a risk of bleeding when platelets are too low. Though many types of hereditary thrombocytopenia exist, MYH9-related disease is the most common.

Several gene mutations can result in low platelet levels. Typically, a person with hereditary thrombocytopenia is born with these gene mutations.

All forms of hereditary thrombocytopenia are considered rare. It may take a long time to get the correct diagnosis. Among people with genetic clotting, platelet, or bleeding disorders, up to 90% never get a specific diagnosis.

Research from 2019 states that 33 different types of hereditary thrombocytopenia exist. Researchers have also identified 40 genes that may play a role in its development.

Read on for more details on some of the more common types of hereditary thrombocytopenia.

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An error in the MYH9 gene causes this type of thrombocytopenia. The MYH9 gene makes myosin-9, a subunit of the myosin IIA protein, which is essential to normal platelet division.

In MYH9-related disease, thrombocytopenia is mainly due to a lack of functional myosin-9. This is because there are fewer overall platelets, which can make clotting difficult.

Some types of MYH9-related disease include:

  • May-Hegglin anomaly
  • Sebastian syndrome
  • Fechtner syndrome
  • Epstein syndrome

Generally, people with MYH9-related disease are at risk of developing the following:

Wiskott-Aldrich syndrome (WAS) affects about 1–10 males per million globally. It is more rare among females.

Changes to the WAS gene cause this condition. The WAS gene codes for WASP protein, an essential component of white blood cells and platelets. As a result, people with WAS tend to have low immune function, and their blood does not clot as it should.

When platelets lack WASP, it leads to reduced platelet size and platelet cells dying too soon. These changes significantly lower the number of platelets and affect bleeding. Eczema and ear infections are some other characteristics of WAS.

A bone marrow transplant is considered a cure for WAS. Untreated, the life expectancy for those with WAS is around 15 years.

X-linked thrombocytopenia

WAS is very similar to another condition known as X-linked thrombocytopenia. Due to their similarities, WAS and X-linked thrombocytopenia are often grouped together. X-linked thrombocytopenia does not decrease immune function as much as WAS.

This group of disorders accounts for about 4.2 to 5.6% of all inherited thrombocytopenia cases.

Many people with ACTN1-related disorders never have any issues with bleeding. Also, people are typically unlikely to experience any signs or symptoms.

Experts consider ACTN1-related disorders to be a mild type of thrombocytopenia. Some people with mutations in the ACTN1 gene can have a normal level of platelets.

Initially described in 1948, Bernard-Soulier syndrome is thought to be the first recognized type of hereditary thrombocytopenia. It can occur due to changes in various genes, including:

  • GP1BA
  • GP1BB
  • GP9

The changes tend to affect the shape of the platelets, causing them to become large. Most people with Bernard-Soulier syndrome have very low platelet levels, and stopping bleeding once it starts is difficult.

When both parents carry mutations in any genes related to this condition, their children will likely develop Bernard-Soulier syndrome.

Different types of von Willebrand disease exist. They all affect the VWF gene, which provides instructions for von Willebrand factor, a protein that plays a role in clot formation.

In Type 2B, the von Willebrand factor (VWF), attaches to the platelet at the incorrect time, for example when there is no injury. This prompts the body to get rid of the platelets attached to the VWF, resulting in a lower amount of both platelets and von Willebrand factor in the blood. Lower amounts of both platelets and VWF makes it difficult for a clot to form.

Among people with hereditary thrombocytopenia, only 18% have ANKRD26-related disorders. Cases tend to mild compared with other types of hereditary thrombocytopenia. People with this condition usually have platelet levels at the low end of the typical range.

Changes in the ANKRD26 gene reduce the number of platelets made by the bone marrow. People with ANKRD26-related disorders also carry a higher risk of developing some types of blood cancers. One study found that 8% of people with ANKRD26-related disorders had myelodysplastic syndromes.

Below are some common questions on hereditary thrombocytopenia.

What is the most common cause of congenital thrombocytopenia?

MYH9-related disease is considered the most common type of hereditary thrombocytopenia. Beyond that, it is hard to get accurate data.

While different genetic causes of thrombocytopenia exist, they are considered rare. Researchers estimate that about 50% of people with hereditary thrombocytopenia do not have an exact diagnosis.

What is the treatment for inherited thrombocytopenia?

A platelet transfusion is the main treatment for people with inherited thrombocytopenia, regardless of the specific cause or type. This treatment method brings the platelet count closer to a healthy level and reduces the risk of bleeding. A bone marrow transplant can be helpful for people with WAS.

Sometimes, medication can help. One example is eltrombopag, which stimulates the bone marrow to make more platelets.

Doctors may consider surgical spleen removal for X-linked thrombocytopenia and WAS. A splenectomy keeps platelets in the body for longer, rather than having them broken down by the spleen. This is not a suitable treatment method for other types of hereditary thrombocytopenia.

What is acquired thrombocytopenia?

Acquired thrombocytopenia is another cause of low platelet levels. One key difference is that a genetic mutation is unlikely to be the cause of acquired thrombocytopenia.

A person with acquired thrombocytopenia may find that platelet levels drop due to the following reasons:

  • side effects of certain medications
  • some types of cancer, including leukemia and lymphoma
  • an infection that temporarily reduces a person’s platelet levels
  • chemotherapy or radiation treatments
  • exposure to some toxic chemicals that can reduce the body’s ability to make platelets

Hereditary thrombocytopenia refers to inherited conditions that cause a low platelet level. Platelets are the part of blood that helps with normal clotting. Another feature of inherited thrombocytopenia is that platelets function abnormally. People with low platelet levels are at risk of internal or external bleeding.

All types of hereditary thrombocytopenia are rare. Still, some types, such as MHY9-related disease, are more common than others. Other types of hereditary thrombocytopenia include WAS, Bernard-Soulier syndrome, ACTN1-related disorders, von Willebrand Type 2B, and ANKRD26-related disorders.

Treatments for different types of hereditary thrombocytopenia are similar. The goal is to increase platelet count to support healthy clotting.