What Is Bernard-Soulier Syndrome?

Excessive bleeding, even from minor cuts, frequent nosebleeds (epistaxis), and the presence of petechiae on your skin could all indicate the possibility of having a severe and extremely rare genetic condition called Bernard-Soulier syndrome (BSS).  

BSS is an inherited, blood-related disorder that is characterised by excessive bleeding and bruises due to a fault in the blood clotting mechanism.

BSS is an extremely rare disease when looking at global statistics. However, it is also often misdiagnosed with other bleeding disorders that are linked to blood clotting. 

Overview

Bernard-Soulier syndrome (BSS) is a blood clotting disorder affecting the GPIb-IX-V protein complex, which is found on the surface of platelets (the cells in your blood responsible for blood clot formation).¹ For people affected with BSS, the GPIb-IX-V complex is either found in the body at lower levels than normal or its ability to bind to von Willebrand Factor (vWF) is reduced. vWF is a blood protein involved in the process of thrombosis (the process of clot formation in a blood vessel), and hemostasis (the process of stopping bleeding).² vWF and GPIb-IX-V binding is essential for platelet aggregation at the site of injury to form a blood clot and to stop bleeding.

This condition is extremely rare, affecting approximately one in a million people. It is most frequently diagnosed in families where very close relatives (e.g. first cousins) have children together. 

What is Bernard-Soulier syndrome?

BSS is an inherited bleeding disorder, mostly found in consanguineous families (closely blood-related people). This condition is extremely rare, with an approximate incidence of it being around one in one million people worldwide. In most cases, BSS is caused by an autosomal recessive pattern. This means both parents must have a copy of the disease-causing mutation to be able to pass it down to their children. However, there have been incidences of individuals having BSS due to an autosomal dominant mutation. In these cases, the disease can be passed down even when only one parent has a copy of the mutation.

BSS results in excessive bleeding, both external and internal. The condition can be characterised by the observation of abnormally large platelets in the blood, as well as impaired platelet function. Heterozygous carriers of BSS, those who carry two different copies of a gene, tend to be asymptomatic. If both parents are carriers for BSS, and the disease is following an autosomal recessive fashion, there is a 25% chance that their child will have BSS, a 50% chance the child will also be a carrier and a 25% that the child will be unaffected.³

Causes

The cause of BSS is genetic. Mutations of three specific genes have been associated with the development of BSS. These genes include:⁴

• GP1BA
• GP1BB
• GP9
• GP5 - possible association

GP1BA, GP1BB, and GP9 genes encode for proteins that make up the GPIb-IX-V protein complex, which plays a role in the blood clotting process. Therefore, defects in these genes can interfere with blood clotting.

Signs and Symptoms

BSS shares symptoms with other blood clotting disorders and is, therefore, often misdiagnosed. 

The main symptoms include:

• Bleeding gums 
• Heavy menstrual periods (menorrhagia)
• Gastrointestinal tract bleeding
• Excessive bleeding
• Low platelet count (thrombocytopenia)
• Giant platelets 

Diagnosis

BSS is often misdiagnosed and underreported. The most common condition that BSS is mistaken with is immune thrombocytopenic purpura. It can also be mistaken for von Willebrand's disease, as the symptoms are very similar.⁴

Certain diagnostic tests are used to diagnose BSS. These include:

• Platelet aggregation studies - Tests are used to measure the time it takes for platelets to aggregate at the site of injury. In BSS cases, the time it takes for platelets to aggregate is prolonged
• Blood smear analysis - BSS is associated with macrothrombocytopenia (enlarged platelets) and thrombocytopenia (reduced number of platelets available), which can be observed on a blood smear under a microscope
• Flow cytometry - This test can be used to observe specific cell markers to quantify the number of platelets in the blood
• Genetic testing - Genetic tests can identify mutations in the GP1BB, GP1BA, and GP9 genes

Treatment

BSS can be life-threatening as it puts you at risk of excessive bleeding. Available treatment options aim to restore your body’s ability to form blood clots. Treatment includes:⁵  

• Blood and platelet transfusions - This procedure is done to replace missing platelets and stimulate blood clotting
• Recombinant therapies - Clotting factors, such as proconvertin, can be administered into an affected individual to promote blood clotting and to reduce bleeding time

FAQs

What is Bernard-Soulier syndrome?

BSS is an inherited disorder that results in excessive bleeding due to a fault in the blood clotting process.

How is Bernard-Soulier syndrome diagnosed?

BSS is mainly diagnosed using flow cytometry, microscopic studies, and genetic testing.

Is Bernard-Soulier syndrome inherited?

Yes, BSS is an inherited condition that can be inherited in an autosomal recessive and autosomal dominant fashion. Mutations in genes linked to BSS are associated with the GPIb-IX-V complex.

How is Bernard-Soulier syndrome managed?

There is no cure for BSS. However, medication for the treatment of excessive bleeding is available. It is important to always be cautious to prevent any unwanted injuries and avoid blood loss. Avoiding engagement in contact sports, such as boxing, and brushing your teeth with a soft toothbrush are small steps that can be taken to prevent injuries that can cause bleeding. 

What are the complications of BSS?

Possible complications of BSS are anaemia, organ damage, and death.

What are the main symptoms associated with BSS?

The major symptoms of BSS are excessive bleeding, epistaxis (nosebleeds), bleeding gums, prolonged bleeding time, and heavy menstrual periods.

Summary

Bernard-Soulier Syndrome (BSS) is a disease which affects the body’s ability to form blood clots, resulting in excessive bleeding. It can be life-threatening if patients are not aware of their condition and if it is left untreated. However, if diagnosed early, BSS is manageable. There is no cure but treatment options are available, including platelet transfusions and recombinant therapies. The most common signs of BSS are the presence of large platelets, prolonged platelet aggregation, and the presence of a mutation in the GP1BB, GP1BA, or GP9 gene.