Glanzmann’s Disease

Glanzmann thrombasthenia is a rare inherited bleeding disorder that causes people to bruise and bleed easily throughout their lives. With only about 1 in 1 million people worldwide affected, this lifelong condition involves a problem with platelets that prevents blood from clotting properly.

Table of contents

• What is Glanzmann’s disease?
• How common is this condition?
• What causes Glanzmann’s disease?
• What are the symptoms?
• Possible complications
• How is it diagnosed?
• Treatment options
• Living with Glanzmann’s disease

Glanzmann thrombasthenia, GT, thrombasthenia of Glanzmann and Naegeli

What is Glanzmann’s disease?

Glanzmann’s disease, also known as Glanzmann thrombasthenia (GT), is a chronic (lifelong) condition that causes people to bruise and bleed easily. It involves a problem with platelets, which are tiny blood cells that help blood clot to stop bleeding^[1].

When someone has GT, a genetic mutation prevents their body from making a key protein called integrin alpha IIb/beta 3 (also known as glycoprotein IIb/IIIa). This protein is essential for platelets to stick together and form clots. Without enough of this protein, or when it doesn’t work properly, clots form more slowly, causing people to bleed more than they should^[1][2].

The severity of bleeding varies greatly from person to person. Some people have such mild symptoms they can manage bleeding at home, while others experience severe bleeding that requires emergency care^[1].

The condition was first described in 1918 by Swiss pediatrician Eduard Glanzmann, who noticed patients with a type of bleeding disorder that had normal platelet counts and sizes but showed problems with blood clotting^[2][3].

How common is this condition?

Glanzmann thrombasthenia is extremely rare. Medical experts estimate that only about 1 in 1 million people worldwide are born with GT^[1][2].

However, the condition is more common in certain communities where the gene mutation tends to run in families. In these populations, the number can be as high as 1 in every 200,000 people^[1][2]. Babies are more likely to be born with GT in certain countries in the Middle East, the Canadian provinces of Newfoundland and Labrador, and the Romani community in France^[1][5].

Males and females are affected equally since this is an autosomal recessive condition, meaning it is not linked to sex chromosomes^[2].

What causes Glanzmann’s disease?

Babies born with Glanzmann thrombasthenia inherit a mutation (or error) in genes that control the production of integrin alpha IIb/beta 3. The two genes involved are called ITGA2B and ITGB3, and they are located on chromosome 17^[2][5].

To develop GT, a person must inherit a mutated gene from both parents. This type of inheritance is called autosomal recessive^[1][3]. Most parents don’t realize they carry the mutation because having just one copy of the mutated gene doesn’t cause symptoms. People with one mutated gene and one normal gene are called carriers^[1].

If both parents are carriers, they have a 25% chance of having a child with GT with each pregnancy^[1][5].

Hundreds of different mutations in these genes have been reported. The various genetic changes can lead to different levels of the protein being made or affect how well the protein works^[2][4].

Acquired Glanzmann thrombasthenia

Some people acquire GT later in life, but this is incredibly rare. With acquired GT, the body makes antibodies that attack integrin alpha IIb/beta 3. Many conditions and even some medications can potentially trigger this response. However, the results are the same as with inherited GT: without enough functioning protein, platelets take longer to form clots^[1][2].

What are the symptoms?

People with GT may bleed more than others would with a similar injury. Sometimes, bleeding may start unexpectedly with no clear reason at all^[1].

The most common symptoms of Glanzmann thrombasthenia involve bleeding from the skin and mucous membranes (the lining of the nose, mouth, and other body openings). Common symptoms include^[1][3][4]:

• Bruising easily
• Bleeding gums
• Frequent nosebleeds (epistaxis)
• Purple spots or patches on the skin (purpura)
• Purple, brown or red dots on the skin (petechiae)
• Heavy menstrual bleeding (menorrhagia) in women
• Gastrointestinal bleeding
• Prolonged bleeding after injury, trauma, or surgery (including dental work)

With GT, internal bleeding is much less common than bleeding from the skin or mucous membranes. Bleeding into joints, which is common in hemophilia, is very rare in people with GT^[1][3].

About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage)^[5].

The severity and frequency of bleeding episodes can vary greatly among affected individuals, even within the same family. Interestingly, the amount of protein present doesn’t always predict how severe the bleeding will be. Some people with very little protein have minimal symptoms, while others with more protein may have severe bleeding^[3].

Possible complications

Heavy menstrual bleeding can lead to iron-deficiency anemia, a condition where the body doesn’t have enough iron to make healthy red blood cells^[1].

In severe cases, GT can lead to serious and even life-threatening heavy bleeding during major life events where blood loss is common, such as childbirth and surgery^[1][5].

Another important complication occurs when people need multiple platelet transfusions throughout their lives. The body may develop antibodies against the donated platelets, making future transfusions less effective or ineffective. This is called platelet alloimmunization^[7][8].

How is it diagnosed?

Healthcare providers perform several tests to diagnose GT. This usually happens in childhood when parents notice their child bruises easily, gets frequent or prolonged nosebleeds, or experiences heavy bleeding during or after routine procedures^[1].

Basic laboratory tests show^[4]:

• Normal platelet count and appearance
• Normal prothrombin time and activated partial thromboplastin time (tests that measure how long blood takes to clot)
• Markedly prolonged bleeding time
• Possible decreased red blood cell count due to bleeding

More specialized tests are needed to confirm the diagnosis. Light transmission aggregometry is considered the gold standard diagnostic tool for assessing platelet function. In people with GT, this test shows decreased or absent platelet clumping with most substances that normally cause platelets to stick together. However, platelets respond normally to a substance called ristocetin^[3][4].

Flow cytometry can measure the amount of integrin alpha IIb/beta 3 protein on the platelet surface. This test shows reduced or absent binding of specific antibodies that normally attach to this protein^[4].

Genetic testing can identify mutations in the ITGA2B or ITGB3 genes, confirming the diagnosis^[4][5].

Treatment options

Treatment of GT includes both preventive measures and treatment of specific bleeding episodes^[3][8].

Preventive measures

People with GT should avoid medications that affect platelet function, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)^[3][4]. Good dental hygiene is important to reduce gum bleeding^[3].

Iron or folate supplementation may be needed to treat or prevent anemia. Patients should be vaccinated against hepatitis B due to the infectious risks associated with multiple transfusions^[4][7].

Treating bleeding episodes

For less severe bleeding, local measures such as applying pressure, using fibrin sealants, topical thrombin, or antifibrinolytic medications (like tranexamic acid) may be sufficient^[7][8][11].

For women with heavy menstrual bleeding, hormonal therapy such as birth control pills may help^[11].

For severe bleeding or before surgery, platelet transfusions used to be the main treatment. However, repeated transfusions can lead to the development of antibodies that make future transfusions less effective. To reduce this risk, patients should receive leukocyte-depleted (white blood cell-filtered) platelets and, when possible, HLA-matched platelets^[7][8].

Recombinant activated factor VII (rFVIIa), sold as NovoSeven, has been approved by the U.S. Food and Drug Administration for treating bleeding episodes and managing bleeding around the time of surgery in patients with GT who don’t respond to platelet transfusions or who have developed antibodies to platelets. Studies have shown that this medication is effective and safe^[4][7][8].

Surgical considerations

Patients with Glanzmann thrombasthenia who require surgery should receive platelet transfusions or recombinant factor VIIa before the procedure to prevent excessive bleeding. Additional treatment may be needed based on how well bleeding is controlled^[7].

Future treatments

Hematopoietic stem cell transplantation (bone marrow transplant) is a potential cure for severe cases, but it is controversial because of the risks involved, including the possibility of developing antibodies against platelets^[2][8]. Gene therapy is another possible future option that is currently being researched^[2][8].

Living with Glanzmann’s disease

Living with Glanzmann thrombasthenia presents unique challenges, but many people with this condition lead full and active lives. Studies have shown that nearly 90% of people with GT experience bleeding episodes frequently, with bruising, nosebleeds, and mouth bleeds being most common^[18].

Fatigue is a significant issue for many people with GT, often resulting from anemia due to frequent bleeding and the constant need to be vigilant about preventing bleeding^[18].

About 80% of people in one study reported losing time from work or school because of bleeding. The condition can also affect social activities and, for some, the ability to get a job or pursue further education^[18].

Many people with GT have experienced being suspected of abuse because of extensive bruising. This has sometimes involved investigations by social workers^[18].

Women with GT face additional challenges with heavy and prolonged menstrual periods. Historically, many were told they could never have children because they wouldn’t survive childbirth. However, with proper medical care and planning, pregnancy and childbirth are possible, though they require close monitoring and specialized care^[7][18].

People with GT often need to balance being careful with living their lives fully. As one person with GT explained, learning to manage the condition involves understanding that while caution is necessary, it’s also important not to let the condition prevent you from living^[15].

Many people with GT find it helpful to educate others about their condition and use visible symptoms like bruising as opportunities to raise awareness about this rare disorder^[17].