Introduction

Glanzmann Thrombasthenia is a rare inherited platelet disorder caused by a deficiency of the platelet integrin alpha IIb beta3. It is essential for platelet aggregation. The disease is autosomal recessive inherited, which means each parent has the trait of the disease even though they might not explicitly have the features of the disease. The prevalence is approximately 1 in 1 million.¹

How Is bleeding controlled? 

The process of stopping the bleeding is called homeostasis in the medical field. It works basically in two main stages. Firstly, the smallest blood cells namely platelets, rush to the injury site and form a temporary and weak plug. Secondly, the blood protein called fibrinogen breaks down to fibrin and that links platelets to each other. The second step is responsible for the stabilization of the clot. In GT, the issue occurs during the first phase of hemostasis. Although the platelet count is normal, the platelets don't function properly.²

When an injury occurs, proteins like collagen and ADP (normally outside the bloodstream) trigger the hemostasis process, and a protein called von Willebrand factor (vWF) connects the platelets, starting aggregation. However, the protein needed for this connection is missing in GT patients, thus preventing proper platelet clumping. Recent studies also show that platelets in GT patients are less effective at producing thrombin, a substance needed to convert fibrinogen into fibrin, which helps stabilize the clot as mentioned earlier.³

Clinical manifestations of GT

So, how can we diagnose GT patients? They usually consult their GPs with excessive or easy bruising, nosebleeds (also called epistaxis between doctors), heavy menstrual periods, and excessive bleeding during childbirth, surgeries, or dental procedures. GT mainly causes mucocutaneous bleeding rather than joint and muscle bleeds common in other bleeding disorders. It means the bleeding occurs mostly in the skin or mucous membranes, like gums. It is a really useful tool for differential diagnosis.⁴ 

Children often first present with nosebleeds, so healthcare providers should closely examine the nasal cavity if GT is suspected. Most people with GT are diagnosed early, often within the first year of life, and bleeding may occur after circumcision, sometimes requiring a blood transfusion. Some patients may experience improvement in symptoms as they grow older. The reason behind it is yet to be discovered.

However, the possible explanation might be avoidance from trauma, going into menopause or the change of blood vessels. As we age the blood vessels become more resilient. Females are often diagnosed earlier than males due to heavy menstrual bleeding if they aren’t diagnosed in childhood.⁵ However, some cases of GT remain undiagnosed until significant bleeding occurs following trauma or surgery.⁶

How to manage acute bleeding?

For mild or acute bleeding, the initial steps in managing Glanzmann Thrombasthenia (GT) are similar to those for other bleeding conditions.⁷

• Apply ice
• Local pressure to the bleeding area
• Cauterization
• Sutures

Tranexamic acid, an antifibrinolytic drug, is often used to prevent the breakdown of clots and can be applied as a mouthwash for gum bleeding in some cases. An interesting study demonstrated that packing the nose with strips of cured pork, along with antibiotics, can be an effective treatment for uncontrollable nosebleeds. Of course, if these local measures are insufficient or if the patient is undergoing surgery, additional treatments are necessary. Such as; 

• Platelet transfusion (standard therapy); replacing the patient's non-functioning platelets with healthy ones from a donor
• Recombinant activated clotting factor VII (rFVIIa)

Platelet transfusion is a safe choice. However there are potential risks; like allergic reactions, transmission of blood-borne pathogens, and the development of antibodies that target platelets, known as platelet refractoriness. It occurs when the patient's immune system attacks transfused platelets. The use of leukocyte-depleted platelet transfusions is a potential protector. Leukocytes, or white blood cells, are responsible for immune reactions.

Therefore removing them from the transfused platelets lowers the chances of immune-related complications. Platelets from the same person should be used for elective surgeries to further minimize immune reactions. Doctors should test these patients for antibodies to detect these immune responses early. In women of reproductive age, platelet transfusion is not the first choice. This is because the antibodies developed against transfused platelets can cross the placenta during pregnancy. It might harm the fetus and cause bleeding complications in the newborn.
Recombinant activated clotting factor VII (rFVIIa), has transformed the management of bleeding in GT. It binds to activated platelets and creates a "thrombin burst".That helps convert fibrinogen into fibrin. Essentially, it bypasses the defective primary hemostasis (the first step of blood clotting) and directly activates the secondary phase of clot formation.rFVIIa has proven to be highly effective for managing surgical bleeding in GT patients and is often used off-label for this purpose.⁸

Chronic and preventive management

Managing Glanzmann Thrombasthenia (GT) requires a collaborative approach involving specialists from various medical fields, such as ENT, cardiology, pulmonology, immunology, nephrology, orthopaedics, ophthalmology, and psychiatry/psychology. GT is a chronic disease. As it is the case for all chronic diseases, educating both the patient and their families is crucial. Additionally, GT is a genetic disorder, so family planning and genetic counselling are important considerations for affected families.

Preventive care plays a significant role in managing GT. Even minor, chronic bleeds can lead to complications like iron deficiency anaemia. Therefore blood iron levels should be monitored regularly by the GP. Maybe the most important preventive strategy is avoidance of trauma! Though this can be challenging. Especially for little children and toddlers. They are active and likely to fall. It may be challenging for parents, as well as teachers, to find more suitable games for these children.

How to manage common bleeding symptoms? 

Epistaxis (Nosebleeds)

Nosebleeds are the most common symptom in GT. To prevent them, it's important to keep the nose moist.

• Using humidifiers
• Saline nasal sprays
• Applying an inert gel to keep the nasal mucosa hydrated might be helpful

Dental hygiene

Good oral hygiene is essential to prevent gum bleeding. It occurs daily when for instance brushing the teeth. Maintaining proper dental hygiene, including regular brushing, flossing, and professional dental cleanings, promotes healthier gums and reduces the likelihood of bleeding. People with GT should be extra careful to use soft toothbrushes and avoid rough brushing!

Psychological and social considerations

As with many chronic conditions, the psychosocial impact of GT should not be overlooked. Children with GT might not participate in certain sports and physical activities due to the risk of injury. It can affect their self-esteem and social development.

Women with GT may experience heavy menstrual bleeding. The physical discomfort can lead to social withdrawal during their periods. Females with heavy menses should consult gynaecologists to explore management options that can reduce menstrual bleeding and improve their quality of life. Additionally, access to mental health professionals who can provide counselling and support is important to help patients and families navigate the emotional aspects of living with a chronic bleeding disorder.

Curative treatment

Some of the patients may have severe bleeding that could not be prevented by current medication/treatments. These individuals bleed frequently. It is life-threatening. In such cases, there is now a possible curative option. It is a hematopoietic stem cell transplant (HSCT). During this procedure, the defective blood cells will be replaced by healthy ones from a donor. If a suitable donor is available, which is not always easy, HSCT has been successful in fixing the bleeding problem completely!⁹ Another possible option might be gene editing techniques, like CRISPR-Cas9. They are already being used to treat other blood disorders. In the future, it may be used to treat GT patients.

Summary

Glanzmann Thrombasthenia is a rare disorder affecting the platelets, which are responsible for blood clotting. These patients usually bleed. That leads to problems a huge spectrum of problems, from iron deficiency anaemia caused by chronic bleeding to major life-threatening conditions such as intracranial haemorrhage. To prevent the bleeding there are some precautions to take, such as using humidifiers so the nasal cavity where most of the bleeding occurs can be protected from easily bleeding, careful dental hygiene and trying to avoid trauma.
When bleeding occurs if it is minor, it can be stopped by applying pressure, cold treatment or sutures. If it is major, that platelet transfusion is a logical solution. It is fairly easy but has problems, such as alloimmunization: the development of antibodies against transfused platelets. That risk can be reduced by using leukocyte-deprived blood products from a single person, if possible. Recombinant Factor VIIa is a promising treatment. Now, it is only used for people who have side effects from platelet transfusion but it probably will be widely used shortly. There are some novel curative options for GT that are still being researched, such as HSCT or CRISPR-Cas9. However, they are still experimental and not widely used.