What is Glanzmann's Thrombasthenia?
Your blood contains small, sticky cells called platelets. When you cut or injure a blood vessel and begin to bleed, platelets rush to the site of injury. There, they stick to the blood vessel and try to stop the leak. They also send out a chemical signal that attracts other platelets. Then, those platelets stick to the platelets at the injury site to form a plug that stops the bleed.
Numerous proteins on the surface of platelets help platelets work properly. One type of these proteins is called glycoprotein. Various glycoproteins are found on the platelet surface and work together like a bridge to connect platelets with each other and to the wall of the injured blood vessel (Table below). Each glycoprotein has a specific target, either another platelet or a target in the vessel wall, and a specific role to play in forming the platelet plug.
This is the first part of making a blood clot. If this step doesn’t happen correctly, then it becomes harder for the clotting factors to work in making a stable clot of fibrin strands.
Some of the reasons that platelets do not work as they should are:
There may not be enough platelets
You may have a normal amount of platelets but they might not be functioning
Platelets may not be able to stick to the blood vessel or to each other
Platelets are sometimes not able to send or receive the chemical signals
When any of these happen, a person has a platelet disorder.
Glanzmann’s Thrombasthenia (GT) is a type of platelet function disorder, meaning the platelets aren’t working right. Specifically, patients with GT have a missing or defective glycoprotein (called Glycoprotein IIb/IIIa or “GP 2B-3A”), which is in charge of making the platelets stick together through binding to fibrinogen (clotting factor 1). This means platelets cannot aggregate or clump together to make a plug.
Glanzmann’s Thrombasthenia was first identified in children from a village in the Swiss Alps called Le Valais in 1918 by a pediatrician from Berne, Switzerland, Dr. Eduard Glanzmann. Since then, Glanzmann’s thrombasthenia has been identified in many other populations all over the world.
What causes it?
Humans have 22 pairs of chromosomes (autosomes) plus the sex chromosomes (X and Y). Glanzmann’s Thrombasthenia is an “autosomal recessive” disorder that impacts both males and females. The “recessive” part means you need to inherit one abnormal gene from each of your parents to have the disease. Parents may either have GT (2 abnormal genes) or be “carriers” (one normal and one abnormal gene). The illustrations below show the potential inheritance patterns of an autosomal recessive disorder.
These risks apply to each pregnancy, so if for example both parents are carriers, then each pregnancy has a 1 in 4 chance the child will be affected.
It’s a little more complicated than this in Glanzmann’s Thrombasthenia since there are actually 2 genes, one for the “2A” part and one for the “3B” part. Both of these are on chromosome 17, one of your 22 pairs of chromosomes. Either one can be abnormal and passed on to result in GT.
About one in 1,000,000 people worldwide have the disease. Men and women are affected equally. Children are often diagnosed early in life and usually before the age of five due to serious bleeding episodes. For example, infants with Glanzmann’s Thrombasthenia have more frequent bleeding from gums during teething or losing baby teeth. In some cases, infants will bleed longer than normal after vaccinations. Children with GT also experience frequent nosebleeds and gum bleeding from normal tooth brushing. Women with GT can experience severe bleeding during menstruation (often worse for their first period) and during childbirth. Minor procedures such as dental work can be a major problem, as can major surgery, and may result in bleeding prompting a diagnostic evaluation.
What are the symptoms?
The most common types of bleeding seen in patients with Glanzmann’s Thrombasthenia include:
Petechiae - small red or purple spots on the skin caused by a minor broken capillary
Bleeding from the nose or gums
Heavy menstruation (in women)
Excessive bleeding after surgery or injury
Excessive bleeding after child birth
Less common types of bleeding seen in patients with Glanzmann’s Thrombasthenia include:
Bleeding into head and brain (headache, neck ache, drowsiness, loss of consciousness)
Bleeding into gastrointestinal tract (vomiting blood, bloody or black bowel movements)
In contrast to patients with more common bleeding disorders like congenital hemophilia A or B, patients with Glanzmann’s Thrombasthenia tend to have more mucocutaneous bleeding, or bleeding involving mucous membranes (nose, mouth, stomach) and skin, but do not tend to experience joint or muscle bleeding.