What is Glanzmann Thrombasthenia?
Glanzmann thrombasthenia (GT), identified first in 1918, is a hereditary bleeding disorder. It’s caused by an issue or deficiency with a protein in the blood platelets called “integrin alpha IIb beta3”. This integrin is like a key that allows blood platelets to stick together (aggregate) and stop bleeding, acting as a blood clotting aid. If you have GT, you will experience bleeding episodes throughout your life, often involving the skins and mucous membranes such as the mouth or the nose.
What Causes Glanzmann Thrombasthenia?
Glansmann Thrombasthenia (GT) is a genetic disorder that is passed down through families (autosomal recessive). This means that a child would need to inherit the faulty gene from both parents to have the condition. The disorder comes from changes or mutations in the genes ITGA2B or ITGB3, which are located on a part of the chromosome 17q21.
There are hundreds of known mutations that can cause GT, and a person can either have two copies of the same mutation or two different mutations to develop the condition. Depending on the specific mutations, the function and level of a protein called alpha IIb beta 3 integrin can vary. For instance, a mutation type called the Manouche mutation leads to no production of this protein at all.
There is also a form of GT that isn’t inherited but is caused by the body mistakenly attacking a protein on the surface of platelets, a type of blood cell that aids clotting. This is known as an autoantibody. Certain blood-related conditions, like multiple myeloma, can lead to the development of these autoantibodies. For example, there has been a reported case of an anti-alpha IIb beta3 antibody in a patient with an autoimmune disease called systemic lupus erythematosus. However, these acquired types of GT are very rare, and the term GT is usually used to refer to the inherited form, as described here.
Risk Factors and Frequency for Glanzmann Thrombasthenia
Glanzmann’s thrombasthenia (GT) is a disease that is quite rare in the general population. On average, about 1 in 1,000,000 people have it. However, in some specific areas where close family marriages are more common, the rate can be as high as 1 in 200,000 people or more. Places like Pakistan and the Canadian provinces Newfoundland and Labrador have a notably high number of GT patients.
Some people with a mild version of the disease might not even know they have it, meaning that the actual numbers could potentially be higher. Research also indicates that women are slightly more likely to have the disease than men. Although GT is often diagnosed in children and young adults, it can affect people of any age.
- GT’s estimated prevalence is about 1:1,000,000 in the general population.
- The prevalence might reach 1:200,000 in areas with a high rate of close family marriages.
- Pakistan and Newfoundland and Labrador in Canada have a higher prevalence.
- Some people with mild symptoms might not be recognized as having GT; therefore the actual prevalence may be higher.
- Women are slightly more likely to have the disease than men.
- While children and young adults are commonly diagnosed with GT, it can affect any age.
Signs and Symptoms of Glanzmann Thrombasthenia
Glanzmann thrombasthenia is a condition that doctors usually identify by checking a patient’s history of unexplained bleeding and bruising. They might also consider a family history of similar symptoms. This condition is most often identified in children, with nosebleeds being a common sign. Other signs might include heavy periods and bleeding gums. Some patients have reported gastrointestinal bleeding, but this is less common. Diagnosis often occurs at a young age, usually with symptoms appearing during the first year of life.
It’s worth noting that a patient might not be diagnosed until after undergoing a medical procedure. Some children might experience significant bleeding after circumcision, to the extent that a blood transfusion is needed. However, many patients find that their symptoms improve as they get older. Doctors may use a special screening tool to identify any abnormalities related to this condition.
According to a voluntary patient registry, the majority of Glanzmann thrombasthenia patients experienced their first symptoms around the age of one. The average age at which the first symptoms occur is approximately 5.6 years. 85% of patients in this registry had been diagnosed by the age of 14.
When a doctor examines a patient suspected of having Glanzmann thrombasthenia, they primarily look for signs of bleeding and its after-effects, like bruises. They also pay close attention to the patient’s nasal cavity, since nosebleeds are a common symptom of the condition.
Testing for Glanzmann Thrombasthenia
The International Society on Thrombosis and Haemostasis (ISTH), specifically the team focused on platelet function, have shared advice on how to diagnose Glanzmann’s Thrombasthenia (GT) and other hereditary platelet function disorders. Their step-by-step guideline suggests that if you have noticeable bleeding issues, preliminary lab tests may be needed. These tests include a complete blood count (CBC), activated partial thromboplastin time (PTT), prothrombin time, along with tests for von Willebrand disease which check von Willebrand Factor (vWF) antigen, ristocetin cofactor activity, and factor VIII coagulant activity. These tests help to discard more common reasons for bleeding and are usually normal in GT and other inherited platelet function disorders.
In later stages of the evaluation, more detailed analysis on the function of your blood platelets could be done or advanced sequencing of your genes. Initial screening might include a blood smear (where they spread a sample of your blood onto a microscope slide), light transmission aggregometry (LTA), a test checking how well your platelets release granules, and flow cytometry which is a technique to look at the surface proteins on your platelets.
LTA is the most reliable test and shows changes in how your platelets clump together in response to specific triggers, apart from ristocetin (a drug that affects the blood clotting process). Flow cytometry usually reveals flawed expression of alpha IIb beta 3 integrin (a protein that helps platelets stick together), although there can be exceptions where defective integrins are seemingly normal. The components of this integrin are identified as CD41 (alpha IIb) and CD61 (beta 3). CD42b, a protein crucial for bonding with vWF, should be expressed normally. However, ISTH didn’t recommend the Platelet Function Analyzer (PFA) test. This test imitates a damaged inner lining of blood vessels and it measures the time taken for a clot to form, which is usually longer if you have GT.
Further tests could include clot retraction, which is often flawed in patients with GT. If your case remains undiagnosed even after these laboratory studies, the ISTH guide suggests including molecular genetic tests which can identify gene mutations in ITGA2B or ITGB3, common in people with GT.
Treatment Options for Glanzmann Thrombasthenia
Glanzmann Thrombasthenia (GT) is a bleeding disorder and its treatment often depends on how severe the symptoms are. In cases where the bleeding isn’t too severe, the patient might receive treatment like local pressure, using heat to stop bleeding (cauterization), stitches, or ice therapy. Certain anti-bleeding medicines, such as tranexamic acid, can be used to prevent gum bleeding in some cases. There are times when conventional treatments may not work well, and the patient might be treated with salt pork packing alongside antibiotics.
If these local treatments don’t fully stop the bleeding, or if the patient needs surgery, they might receive a platelet transfusion or a medication known as recombinant activated clotting factor VII (rFVIIa). Platelet transfusion is a standard treatment for moderate to severe cases of GT, as it helps in the prevention of surgical bleeding. Recombinant FVIIa works by binding to activated platelets and fostering a rapid creation of thrombin, a protein critical for clotting. That aids converting a protein called fibrinogen into fibrin, which helps stop bleeding.
There can be instances where rFVIIa may not be effective in some patients. Also, it’s important to note that women with GT, who have heavy menstrual bleeding (menorrhagia), might need additional treatment and should also be tested for iron deficiency. Anti-bleeding medicines are typically the first line of treatment for menorrhagia, but continuous hormone supplementation can also be used to prevent it. In cases of severe bleeding during the onset of menstruation (menarche), immediate treatment with high-dose estrogen followed by continuous use of birth control pills could be considered.
Surgical procedures like endometrial ablation (removal of the lining of the uterus) or hysterectomy (removal of the uterus) are options for women who do not wish to maintain their fertility. For those who are pregnant and planning a vaginal birth, it’s recommended to use preventative medications such as a anti-bleeding drug or rFVIIa. If the mother is having a cesarean section, it’s also recommended to have rFVIIa as a preventative measure.
Most patients do well with preventative strategies and treatment of symptoms. However, if a patient’s quality of life significantly worsens due to GT, a more radical treatment via hematopoietic stem cell transplant may be beneficial. Before undergoing such a procedure, the patient’s overall health and circumstances must be thoroughly evaluated to weigh the potential benefits and risks of the transplant.
What else can Glanzmann Thrombasthenia be?
If a person with Glanzmann’s Thrombasthenia (GT) starts bleeding, there are many different conditions that might be causing the problem. These include:
- A low platelet count, known as thrombocytopenia
- Problems with how the platelets function, which can happen with taking certain medications like NSAIDs
- Hermansky-Pudlak syndrome
- Von Willebrand disease
- Bernard-Soulier syndrome
There are other conditions that can cause problems with platelets functioning properly, but they are less likely. These include:
- Gray platelet syndrome
- Medich platelet syndrome
- Scott syndrome
What to expect with Glanzmann Thrombasthenia
Glanzmann’s Thrombasthenia (GT) is a severe disorder that can cause serious bleeding. This bleeding can occur suddenly or be triggered by invasive procedures, severe injuries, or childbirth. It can sometimes be life-threatening or even fatal.
This condition can present itself in many different ways due to the various genetic causes. This means the severity and symptoms can vary greatly from person to person. However, with good preparation and coordination by the healthcare team, patients can still do well. For example, there was a 52-year-old man with GT who successfully underwent an open aortic valve replacement surgery.
In general, the bleeding episodes experienced by individuals with GT are not usually as life-threatening as those associated with inherited disorders that affect blood clotting.
Possible Complications When Diagnosed with Glanzmann Thrombasthenia
People with GT (Glanzmann Thrombasthenia), a rare blood disorder, can suffer from iron deficiency anemia due to chronic mild bleeding. However, more often, the challenges faced by GT patients come not from the disease itself, but from its treatment.
Roughly 17% of GT patients who are treated with specific blood cell components, known as leukocyte-reduced platelets, develop antibodies against these cells. This percentage can dramatically increase if leukocyte-reduced platelets aren’t used. For half of these patients, the antibodies may make future platelet transfusions less effective. Some patients can also develop antibodies to certain proteins involved in blood clotting. Moreover, GT patients can develop antibodies against platelets. These antibodies can cross the placenta and cause a variety of effects in the fetus – from low platelet counts to fatal intracranial bleeding.
Common GT complications:
- Iron deficiency anemia due to mild chronic bleeding
- Development of anti-HLA antibodies leading to resistance to future platelet transfusions
- Antibodies against the alpha IIb beta 3 integrin protein
- Developing anti-platelet antibodies
- In pregnant women, potential risks to the fetus, including low platelet count or fatal intracranial bleeding
Preventing Glanzmann Thrombasthenia
If you have GT (Glanzmann’s Thrombasthenia), a rare blood clotting disorder, it’s important for you to learn how to spot any unusual bleeding. Try to avoid situations where you could get hurt unnecessarily and don’t take any medications that might interfere with how your blood platelets work. Platelets are tiny blood cells that help your body form clots to stop bleeding.
Keeping your teeth and gums clean is also crucial, as poor dental hygiene can lead to bleeding problems. There are certain groups of patients who need to be extra careful and pay more attention, such as young women who might experience heavy bleeding during their menstrual period.
Planning your family is another area where GT might affect your decisions. You need to be mindful of the risks associated with pregnancy and childbirth and also the possibility of passing the condition onto your children. These are important conversations to have if GT is something you have to manage in your life.
