Introduction

Glanzmann thrombasthenia (GT) is a rare congenital blood disorder, characterised by the inability of specialised cells called platelets to clot blood properly at birth.¹ Thus, bleeding occurs excessively and is more difficult to stop after an injury.²

Pronunciation: GLAHNZ-mahn throm-bahss-THEE-nee-uh.

The basics of blood clotting

Blood clotting, also known as coagulation, is the process that your body applies to stop bleeding when you cut yourself. During an injury, blood vessels (i.e., the tubes that carry blood around the body) become damaged and cause the blood to ‘leak’ into the surrounding areas.³ The injury triggers tiny cells called platelets within the blood vessels to rush to the site of the cut and start sticking together to form a small plug (i.e., a clot) to block the hole and prevent you from bleeding out.³ This is accompanied by a series of ‘clotting factors’ as part of the coagulation cascade, which strengthen the clot and result in the formation of a protein called fibrin, that forms a mesh to stabilise the clot and stop bleeding as the wound heals.³

Genetic cause of glanzmann thrombasthenia

Glanzmann thrombasthenia is caused by a genetic mutation, or defect, that affects the platelets in the blood. The mutations are specifically in the ITGA2B or ITGB3 genes.² These genes produce proteins that are part of a receptor on the surface of platelets called glycoprotein IIb/IIIa (GPIIb/IIIa).¹ Usually, GPIIb/IIIa helps platelets bind to each other (i.e., aggregate) and form stable blood clots, which stop the bleeding.² However, in GT, the genetic mutations cause the GPIIb/IIIa receptors to either be absent, defective, or present in reduced numbers, so platelets cannot properly stick together and form a complete blood clot.² Consequently, people with GT bleed more often and for longer periods.

Since GT is a genetic condition, it is usually inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the defective gene, one from each parent, to develop the disorder and display the symptoms.¹

Clinical presentation of glanzmann thrombasthenia

The signs and symptoms of GT may begin to appear as a newborn and as an infant, and will vary from person to person:⁴

• Prolonged bleeding time
• Bruising
• Epistaxis (i.e., nosebleed)
• Gingival bleeding (i.e., gum bleed)
• Menorrhagia (i.e., heavy menstrual bleeding)
• Purpura (i.e., reddish-purple spots on the skin)
• Prolonged bleeding after surgery
• Impaired platelet aggregation

Diagnostic tests for glanzmann thrombasthenia

The majority of individuals with GT are diagnosed at an early age, and symptoms may appear soon after birth.² There are several key diagnostic tests for GT, but when a healthcare provider evaluates you for this disorder, they consider your bleeding history, along with your family’s, to aid in the diagnostic procedure.

The following diagnostic tests are often performed for GT:

• Complete blood count (CBC)
• Blood smear
• Platelet aggregation test
• Light transmission aggregometry (LTA)
• Prothrombin time (PT) test and partial thromboplastin time (PTT) test
• Flow cytometry
• Genetic testing

Complete blood count (CBC)

A CBC is a basic blood test that determines the number of blood cells, such as platelets.⁵ In Glanzmann thrombasthenia, the number of platelets is usually normal, but they do not function properly due to either an absence or a reduced number of surface receptors on the platelets that are needed to initiate the ‘sticking’ of these specialised cells.

Blood smear

A sample of blood is examined under a microscope to check the shape and appearance of platelets.⁵ In Glanzmann thrombasthenia, the platelets look normal but do not clump properly.

Platelet aggregation test

This test determines how well the platelets in the blood clump together. In Glanzmann thrombasthenia, the platelet aggregation study results are abnormal, as the platelets are not able to clump together when they’re stimulated to form aggregates.¹

GT is often characterised by the inability of platelets to form aggregates.⁶

Light transmission aggregometry (LTA)

LTA is a laboratory test that is a measurement of platelet function in patients with platelet function disorders (PFDs), and it assesses how well platelets in the blood clump together, which is a necessary step in the formation of a stable blood clot.⁷

LTA is considered the gold standard diagnostic test for assessing platelet function.²

In LTA, a sample of blood is drawn, and the platelet-rich plasma (i.e., the liquid part of blood containing a high concentration of platelets) is separated out.7 Various substances, known as agonists, are added to the plasma, and these include ADP, thrombin, collagen or epinephrine, and ristocetin. In a normal scenario, the platelets should clump together, but in those with Glanzmann thrombasthenia, the platelets won’t clump together properly with all agonists except ristocetin.⁷

PT and PTT tests

The prothrombin time (PT) and partial thromboplastin time (PTT) tests reveal how well your blood clots and are often employed to rule out other common bleeding disorders like Bernard-Soulier syndrome or von Willebrand disease.⁵

Flow cytometry

Flow cytometry is an advanced test that checks for specific proteins on the surface of platelets, and in Glanzmann thrombasthenia, there is defective expression of CD41 (alpha IIb) and CD61 (beta3) surface proteins.¹

Genetic testing

Genetic tests help locate mutations, or changes, in the genes that are responsible for producing the proteins that help platelets stick together, such as ITGA2B and ITGB3.⁵

Syndromes like glanzmann thrombasthenia

It is important to note that there are other rare inherited disorders with similar symptoms to GT, so differentiating between them is crucial for making an accurate diagnosis and providing correct treatments.¹

Haemophilia

Haemophilia is also a rare inherited disorder that involves abnormal clotting of the blood, but it is usually caused by an inactive or absent blood protein called factor VIII or IX, which are both required for the normal clotting of blood.¹  Those diagnosed with haemophilia may bleed more spontaneously and for a prolonged time.

Bernard-soulier syndrome

Bernard-Soulier syndrome is also a rare inherited blood clotting disorder, and it is characterised by abnormally sized platelets, including very large, or giant, and do not adhere properly to blood vessels. People with this condition also bleed more frequently and have a tendency to bruise easily.¹

FAQs

How common is glanzmann thrombasthenia?

The frequency of Glanzmann thrombasthenia is estimated to be 1:1,000,000 in the population.²

What do bernard-soulier syndrome and glanzmann thrombasthenia have in common?

Both Bernard-Soulier syndrome and Glanzmann thrombasthenia affect about 1 in 1 million people, and are autosomal recessive disorders, meaning that an affected person inherits two copies of the defective gene, one from each parent.⁸

What is the life expectancy of someone with Glanzmann thrombasthenia?

With appropriate management and treatment of the condition, most people with Glanzmann thrombasthenia (GT) have an average life expectancy.⁵

What questions should I ask my healthcare provider?

If you or a loved one has Glanzmann thrombasthenia, it is crucial to have thorough discussions with your healthcare provider to understand the condition and manage it effectively.

Questions to ask include:

• Are there any specific tests that should be repeated regularly?
• What symptoms should I watch out for that would require immediate medical attention?
• What are the current treatment options for Glanzmann thrombasthenia?
• What medications or therapies are recommended for me, and are there any side effects?
• Are there any activities I should avoid to reduce the risk of injury or bleeding?
• What should I do in the event of a serious bleeding episode?

Summary

Glanzmann thrombasthenia (GT) is a rare inherited blood-clotting disorder that affects around 1 in 1 million people in the population. It is characterised by the inability of platelets to form blood clots, an essential step that promotes wound healing. It is caused by mutations in ITGA2B or ITGB3 genes, which produce proteins called glycoprotein IIb/IIIa (GPIIb/IIIa) that are present on the surface of platelets within the blood. These proteins usually facilitate the aggregation of platelets, helping them clump together to form a stable blood clot. However, in people with GT, these proteins are either defective, absent, or present in reduced numbers, and the platelets are unable to stick together effectively.

As a result, the platelets cannot form proper blood clots, which is a fundamental step in wound healing. This results in prolonged bleeding and slow healing of the cut or injury site. Symptoms of GT vary from person to person; however, most people with the disorder have some shared characteristics, such as a prolonged bleeding time, bruising, nosebleeds, and gum bleeds, as well as heavy menstrual bleeding. Diagnostic tests include a complete blood count, blood smear, LTA, and flow cytometry aid. These tests usually determine the ability of platelets to clump together properly and bind to certain agonists, such as ADP, collagen, and ristocetin, the latter of which binds normally to platelets and is often a diagnostic clue to the presence of the condition. The symptoms of GT overlap with the symptoms of some other conditions, such as haemophilia and Bernard-Soulier syndrome, which also involve excessive bleeding. Therefore, you must advise a healthcare professional if you experience any of these symptoms in excess.